1, 3, 4-oxadiazoles and derivatives thereof as novel antifungal agents
阅读说明：本技术 作为新的抗真菌剂的1，3，4-噁二唑及其衍生物 (1, 3, 4-oxadiazoles and derivatives thereof as novel antifungal agents ) 是由 S·布吕内 P-Y·科奎罗恩 P·德斯博德斯 S·杜塞夫 J·杜弗尔 A·格茨 E·希尔 于 2019-12-20 设计创作，主要内容包括：本公开内容涉及1,3,4-噁二唑及其衍生物作为杀真菌剂的用途。其还涉及新的1,3,4-噁二唑衍生物、其作为杀真菌剂的用途和包含其的组合物。(The present disclosure relates to the use of 1, 3, 4-oxadiazoles and derivatives thereof as fungicides. It also relates to novel 1, 3, 4-oxadiazole derivatives, their use as fungicides and compositions comprising them.)
1. use of a compound of formula (I) or a salt, N-oxide or solvate thereof for controlling phytopathogenic fungi:
wherein
U is C containing 2 to 7 halogen atoms1-C3-haloalkyl groups, the halogen atoms being identical or different and selected from fluorine and chlorine;
Q1is O or S;
W1and W2Independently N, CH or CF;
a is selected from direct bond, O, S, S ═ O, S (═ O)2、NR4、-(C＝O)-、-(C＝S)-、-O-(C＝O)、-O-(C＝S)-、-N(R4)-(C＝O)-、-N(R4)-(C＝S)-、-(C＝O)-O-、-(C＝S)-O-、-(C＝O)-N(R5)-、-(C＝S)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-(C＝S)-N(R4)-N(R5)-、-O-N(R5)-、-N(R4)-O-、-N(R4)-N(R5)-、-O-(C＝O)-N(R5)-、-O-(C＝S)-N(R5)-、-N(R4)-(C＝O)-O-、-N(R4)-(C＝S)-O-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5) -, -O- (C ═ O) -O-and-O- (C ═ S) -O-;
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0, 1 or 2;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, aminocarbonyl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkenyl, C2-C8-haloalkenyl, C2-C8-alkynyl, C2-C8-haloalkynyl, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C 1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C2-C8-alkenyl and C2-C8Alkynyl may be interrupted by one or more R1aAnd R2aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl groups may be independently substituted by one or more R1bAnd R2bSubstituent group substitution; or
R1And R2May be taken together with the carbon atom to which they are attachedForm C3-C7-cycloalkyl or a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, wherein C is3-C7Cycloalkyl and a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring may be interrupted by one or more R1bSubstituent group substitution; or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring, wherein said C3-C7The cycloalkyl ring may be interrupted by one or more R1bSubstituent group substitution;
R3is hydrogen, halogen, borono, (trifluoro) boron alkyl potassium, di- (C)1-C8-alkoxy) boryl, 1, 3, 2-dioxaborolan-2-yl, C 1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein the 1, 3, 2-dioxaborolan-2-yl and 1, 3, 2-dioxaborolan-2-yl groups may be substituted by one to four C1-C3-alkyl substituents, and wherein said C is1-C8Alkyl may be substituted by one or more R3aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8The alkyl radical mayBy one or more R3bSubstituent group substitution;
R4and R5Independently selected from hydrogen atom, hydroxyl, C1-C8Alkyl radical, C1-C8-haloalkyl, hydroxy, C1-C8-alkoxy, C1-C8-haloalkoxy, C2-C8-alkenyl, C2-C8-haloalkenyl, C3-C8-alkynyl, C3-C8-haloalkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, formyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, arylcarbonyl, C 1-C8Alkoxycarbonyl, C1-C8-haloalkoxycarbonyl, C1-C8-alkylsulfonyl, C1-C8Haloalkylsulfonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C2-C8-alkenyl, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8Alkoxycarbonyl and C1-C8The alkylsulfonyl radicals may be independently substituted by one or more R4aAnd R5aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, arylcarbonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8The alkyl and phenylsulfonyl groups may each be substituted by one or more R4bAnd R5bSubstituent group substitution;
R1a、R2a、R3a、R4aand R5aIndependently selected from halogen, nitro, hydroxy, cyano, carboxy, amino, sulfanyl, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamateBase, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C 1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
R1b、R2b、R3b、R4band R5bIndependently selected from halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group, amino group, sulfanyl group, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8Haloalkyl, having 1 to 5 halogen atomsC of (A)3-C7-halocycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C 1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
with the proviso that the compound of formula (I) is not:
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6],
-2-isopropyl-5, 6-dimethyl-3- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } pyridin-4-ol [2133324-02-2 ].
2. Use of a compound of formula (I) according to claim 1 or a salt, N-oxide or solvate thereof,
wherein
U is selected from CHF2、CClF2And CF3；
Q1Is O or S;
W1and W2Independently is N or CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0 or 1;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7-cycloalkyl and aryl, wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring;
R3selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy,
Wherein the 1, 3, 2-dioxaborolan-2-yl may be substituted by one to four C1-C3-an alkyl substituent, and (C) a substituted alkyl group,
wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C1-C8-a haloalkoxy substituent, and
wherein said C3-C7-cycloalkyl, C3-C8The cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group;
R4and R5Independently selected from hydrogen, hydroxy, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted by one or two fluorine atoms,
with the proviso that the compound of formula (I) is not:
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6],
And their salts, N-oxides, solvates and optical or geometric isomers.
3. Use of a compound of formula (I) according to claim 1 or 2, or a salt, N-oxide or solvate thereof, wherein
U is selected from CHF2、CClF2And CF3；
Q1Is O or S;
W1and W2Independently is N or CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0;
each R1Independently selected from the group consisting of hydrogen, fluoro, chloro, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl,
or when m is 2, two consecutive R1May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl or cyclopentyl ring, and
each R2Independently selected from hydrogen, fluoro, chloro, methyl, ethyl, trifluoromethyl and difluoromethyl,
or
R1And R2May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring;
R3selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c 3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and naphthyl; a heterocyclyl group selected from the group consisting of tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazacyclohexanyl, oxathiahexidinyl, thiomorpholinyl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, and isoquinolinyl; biphenyl, phenoxyphenyl and phenoxy;
And wherein said C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl;
R4and R5Independently selected from hydrogen, hydroxy, C1-C4Alkyl radical, C1-C4-haloalkyl group, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C4-alkynyl, C1-C4-alkylcarbonyl group, C1-C4-haloalkylcarbonyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted by one or two fluorine atoms;
with the proviso that the compound of formula (I) is not:
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6 ].
4. Use of a compound of formula (I) according to any one of claims 1 to 3, wherein U is CHF, or a salt, N-oxide or solvate thereof 2Or CF3Preferably CHF2。
5. Use of a compound of formula (I) according to any one of claims 1 to 4, wherein a is a direct bond, O, NR, or a salt, N-oxide or solvate thereof4、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5)-。
6. Use of a compound of formula (I) according to any one of claims 1 to 5, or a salt, N-oxide or solvate thereof, wherein
R4And R5Independently selected from hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-difluoroethyl, methoxy, ethoxy, prop-2-ynyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted with one or two fluorine atoms.
7. Use of a compound of formula (I) according to any one of claims 1 to 6, or a salt, N-oxide or solvate thereof, wherein W1And W2Is N, or W1Is N and W2Is CH.
8. A compound of formula (I) according to any one of claims 1 to 7 or a salt, N-oxide or solvent thereofUse of compounds wherein Q1Is O.
9. Use of a compound of formula (I) according to any one of claims 1 to 8, or a salt, N-oxide or solvate thereof, wherein a is O or NR4。
10. Use of a compound of formula (I) according to any one of claims 1 to 9, or a salt, N-oxide or solvate thereof, wherein
U is CHF2Or CF3；
Q1Is O;
p is 0;
W1and W2Is N;
a is O or NH;
m is 1;
R1selected from hydrogen, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C2-C8-alkenyl, C3-C7-cycloalkyl and phenyl;
R2is hydrogen;
or
R1And R2Together with the carbon atom to which they are attached form C3-C7-cycloalkyl or oxa
A cyclobutane-based ring, preferably a cyclopropyl, cyclobutyl or oxetanyl ring; and R is3Is selected from C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl and heteroaryl, where C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;
wherein C is3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl;
wherein aryl is selected from phenyl and naphthyl;
wherein heterocyclyl is selected from piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, morpholin-4-yl, and 1, 3-dihydro-2H-isoindol-2-yl;
wherein heteroaryl is selected from the group consisting of 2-furyl (2-furyl), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, and quinolin-2-yl;
And wherein said C3-C7-cycloalkyl, C3-C8-the cycloalkenyl, aryl, heterocyclyl and heteroaryl groups may be substituted with one to three substituents independently selected from: fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl.
11. Use of a compound of formula (I) according to claim 10 or a salt, N-oxide or solvate thereof, wherein
R1Selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, vinyl, ethynyl, phenyl and cyclopropyl, and
R2is a hydrogen atom, and is,
or
R1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl or oxetanyl ring; and is
R3Selected from phenyl and pyridine, wherein said phenyl and pyridine may be substituted with one to three R3b, said R3b substituent being independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl.
12. A compound of formula (I):
wherein
U is C containing 2 to 7 halogen atoms1-C3-haloalkyl groups, the halogen atoms being identical or different and selected from fluorine and chlorine;
Q1is O or S;
a is selected from a direct bond, O, NR4、S、S＝O、S(＝O)2、-(C＝O)-、-(C＝S)-、-O-(C＝O)-、-O-(C＝S)-、-N(R4)-(C＝O)-、-N(R4)-(C＝S)-、-(C＝O)-O-、-(C＝S)-O-、-(C＝O)-N(R5)-、-(C＝S)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-(C＝S)-N(R4)-N(R5)-、-O-N(R5)-、-N(R4)-O-、-N(R4)-N(R5)-、-O-(C＝O)-N(R5)-、-O-(C＝S)-N(R5)-、-N(R4)-(C＝O)-O-、-N(R4)-(C＝S)-O-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5)-、-O-(C＝O)-O-、-O-(C＝S)-O-；
W1And W2Independently N, CH or CF;
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0, 1 or 2;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkenyl, C2-C8-haloalkenyl, C2-C8-alkynyl, C2-C8-haloalkynyl, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C2-C8-alkenyl and C2-C8Alkynyl may be interrupted by one or more R1aAnd R2aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl groups may be independently substituted by one or more R1bAnd R2bSubstituent group substitution; or
R1And R2May form C together with the carbon atom to which they are attached3-C7-cycloalkyl or a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, wherein C is 3-C7Cycloalkyl and a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring may be interrupted by one or more R1bSubstituent group substitution; or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring, wherein said C3-C7The cycloalkyl ring may be interrupted by one or more R1bSubstituent group substitution;
R3is hydrogen, halogen, borono, (trifluoro) boron alkyl potassium, di- (C)1-C8-alkoxy) boryl, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein the 1, 3, 2-dioxaborolan-2-yl and 1, 3, 2-dioxaborolan-2-yl groups may be substituted by one to four C1-C3-alkyl substituents, and wherein said C is1-C8Alkyl may be substituted by one or more R3aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C 1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl may be substituted by one or more R3bSubstituent group substitution;
R4and R5Independently selected from hydrogen atom, hydroxyl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C2-C8-alkenyl, C2-C8-haloalkenyl, C3-C8-alkynyl, C3-C8-haloalkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, formyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, arylcarbonyl, C1-C8Alkoxycarbonyl, C1-C8-haloalkoxycarbonyl, C1-C8-alkylsulfonyl, C1-C8Haloalkylsulfonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C2-C8-alkenyl, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8Alkoxycarbonyl and C1-C8The alkylsulfonyl radicals may be independently substituted by one or more R4aAnd R5aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, arylcarbonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8The alkyl and phenylsulfonyl groups may each be substituted by one or more R4bAnd R5bSubstituent group substitution;
R1a、R2a、R3a、R4aand R5aIndependently selected from halogen, nitro, hydroxy, cyano, carboxy, amino, sulfanyl, pentafluoro-lambda 6Sulfanyl, formyl, carbamoyl, carbamate, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl having 1 to 5C of halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
R1b、R2b、R3b、R4band R5bIndependently selected from halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group, amino group, sulfanyl group, pentafluoro-lambda 6Sulfanyl, formyl, carbamoyl, carbamate, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8Haloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C2-Cs-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylsulfinyl radical having 1 to 5 halogensC of an element atom1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms 1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
with the proviso that when m is 1 or 2 and W1And W2When N is present, A is not NR4；
Provided that when W1And W2When it is CH, U is not CCl3Or CHCl2；
With the proviso that the compound of formula (I) is not:
-2, 5-bis [5- (trichloromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [222190-08-1],
-2- (bromomethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [2071232-31-8],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-methylpyridine [2071232-29-4],
-2-chloro-5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [2011795-38-1],
-2-chloro-5- [5- (dichloromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [160152-11-4],
-2- {5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -1H-benzimidazole-7-carboxamide [1103394-47-3],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- { (4-fluorophenyl) [1- (methylsulfonyl) azetidin-3-yl ] methyl } pyrimidin-2-amine [2243579-66-8],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (methylsulfonyl) pyrimidine [2095318-34-4],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (methylsulfanyl) pyrimidine [2095318-33-3],
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6],
-N- [2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) -2- (tetrahydro-2H-pyran-4-yl) ethyl ] methanesulfonamide [2243579-65-7],
-1- [4- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) -4-isopropylpiperidin-1-yl ] ethanone [2243579-38-4],
-N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -2, 2-difluoro-N- [1- (4-fluorophenyl) -2- {3- [ (methylsulfonyl) amino ] phenyl } ethyl ] acetamide [2243577-58-2],
-N- [ 2-cyclopropyl-2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) ethyl ] methanesulfonamide [2243577-21-9],
-N- [ 2-cyclopropyl-2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) ethyl ] methanesulfonamide [2243577-20-8],
-N- [ 2-cyclopropyl-2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) ethyl ] methanesulfonamide [2243577-19-5],
-N- [ cyclopropyl (4-fluorophenyl) methyl ] -N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -2, 2-difluoroacetamide [2243576-38-5],
-N- [ cyclopropyl (4-fluorophenyl) methyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine [2243576-35-2],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-isopropylcyclopropyl) pyrimidin-2-amine [2243576-06-7],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- [ (1-phenylcyclopropyl) oxy ] pyrimidine [2243575-46-2], and
-N- [ (6-methylpyridin-2-yl) methyl ] -5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine [2243575-26-8],
-2- (difluoromethyl) -5- (4-iodophenyl) -1, 3, 4-oxadiazole [2244172-62-9],
-2-isopropyl-5, 6-dimethyl-3- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } pyridin-4-ol [2133324-02-2],
-2- [4- (bromomethyl) -3-fluorophenyl ] -5- (trifluoromethyl) -1, 3, 4-oxadiazole [2098919-34-5],
-N- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } butan-1-amine [2080363-69-3],
-2- [4- (chloromethyl) phenyl ] -5- (difluoromethyl) -1, 3, 4-oxadiazole [2071231-55-3],
-2- [4- (bromomethyl) -3-fluorophenyl ] -5- (difluoromethyl) -1, 3, 4-oxadiazole [2071227-85-3],
-2- (difluoromethyl) -5- (3-fluoro-4-methylphenyl) -1, 3, 4-oxadiazole [2071227-84-2],
-1- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } methanamine hydrochloride (1: 1) [2071226-91-8],
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } methanesulfonamide [2071223-51-1],
-methyl 4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [1352872-14-0],
-2- (trifluoromethyl) -5- [4- (trifluoromethyl) phenyl ] -1, 3, 4-oxadiazole [1352872-13-9],
-2- (4-tert-butylphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1352872-12-8],
-2- (4-methylphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1352872-11-7],
methyl- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenoxy } acetate [1227372-86-2],
-ethyl 2- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenoxy } propanoate [1227372-85-1],
-2- (4-bromophenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [918476-23-0],
-4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] aniline [904643-35-2],
-2- ([ biphenyl ] -4-yl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [887267-97-2],
-2- [4- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl ] -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1056456-25-7],
-2- (4-chlorophenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [627073-36-3],
-2- (4-methoxyphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [371950-64-0],
-2- (dichloromethyl) -5- (4-methoxyphenyl) -1, 3, 4-oxadiazole [214195-06-9],
-2- (4-tert-butylphenyl) -5- (dichloromethyl) -1, 3, 4-oxadiazole [160152-26-1],
-2- (dichloromethyl) -5- (4-ethoxyphenyl) -1, 3, 4-oxadiazole [160152-21-6],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-fluoropyridine [2137870-57-4],
-4- [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl ] aniline [2275439-93-3],
-2- ({4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoyl } oxy) -1H-isoindole-1, 3(2H) -dione [2248417-20-9],
-tert-butyl 4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [2241139-66-0],
-methyl 4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [2230804-32-5],
-4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] aniline [2160335-34-0],
-4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzaldehyde [2138236-86-7],
-2- (difluoromethyl) -5- (4-fluorophenyl) -1, 3, 4-oxadiazole [2137866-38-5],
-2- (4-bromophenyl) -5- (difluoromethyl) -1, 3, 4-oxadiazole [2137697-81-3],
-4- [5- (pentafluoroethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1920768-68-8],
-4- [5- (1, 1, 2, 2-tetrafluoroethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1917442-65-9],
-4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1282022-66-5], and
-4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1197226-72-4 ].
13. A compound of formula (I) according to claim 12, wherein
U is selected from CHF2、CClF2And CF3；
Q1Is O or S;
W1and W2Independently is N or CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0 or 1;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7-cycloalkyl and aryl, wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring;
R3selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C 1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy,
wherein the 1, 3, 2-dioxaborolaneAlk-2-yl may be substituted by one to four C1-C3-an alkyl substituent, and (C) a substituted alkyl group,
wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C1-C8-a haloalkoxy substituent, and
wherein said C3-C7-cycloalkyl, C3-C8The cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group;
R4and R5Independently selected from hydrogen, hydroxy, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted by one or two fluorine atoms;
with the proviso that when m is 1 or 2 and W1And W2When N is present, A is not NR4。
14. A compound of formula (I) according to claim 12 or 13, wherein
U is selected from CHF2、CClF2And CF3Especially CHF2Or CF3；
Q1Is O or S, preferably O;
W1and W2Independently is N or CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0;
each R1Independently selected from the group consisting of hydrogen, fluoro, chloro, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl,
or when m is 2, two consecutive R1May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl or cyclopentyl ring, and
each R2Independently selected from hydrogen, fluoro, chloro, methyl, ethyl, trifluoromethyl and difluoromethyl,
or
R1And R2May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring;
R3selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c 3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and naphthyl; a heterocyclyl group selected from tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, pyrrolidinyl, piperidinyl, pyridazinyl, piperidinyl, piperazinyl, piperidinyl, pyrrolidinyl, piperidinyl, pyrimidinyl, piperazinyl, piperidinyl, and pyrrolidinyl,Triazacyclohexanyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazahexanyl, oxathiahexanyl, thiomorpholinyl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, and isoquinolinyl; biphenyl, phenoxyphenyl and phenoxy;
and wherein said C 3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3b(ii) substituent substitution, said R3b substituent being independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl;
preferably, R3Selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and 2-naphthyl; a heterocyclyl group selected from piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, morpholin-4-yl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from 2-furyl (2-furyl), 2-thienyl, 3-thienyl, lH-pyrazol-5-yl, 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxa Oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl and quinolin-2-yl; biphenyl, phenoxyphenyl and phenoxy;
and wherein said C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3b(ii) substituent substitution, said R3b substituent being independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl;
R4and R5Independently selected from hydrogen, hydroxy, C1-C4Alkyl radical, C1-C4-haloalkyl group, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C4-alkynyl, C1-C4-alkylcarbonyl group, C1-C4-haloalkylcarbonyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted by one or two fluorine atoms, preferably R4And R5Independently selected from hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-difluoroethyl, methoxy, ethoxy, prop-2-ynyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted with one or two fluorine atoms;
With the proviso that when m is 1 or 2 and W1And W2When N is present, A is not NR4。
15. A composition comprising at least one compound of formula (I) according to any one of claims 12 to 14 and at least one agriculturally acceptable adjuvant.
16. A method for controlling phytopathogenic fungi, which comprises the step of applying at least one compound of the formula (I) according to any of claims 12 to 14 or a composition according to claim 15 to the plants, to parts of plants, to seeds, to fruits or to the soil in which the plants are growing.
17. The method of claim 16, wherein the phytopathogenic fungus is selected from the group consisting of puccinia species, monascus species and rust pathogens.
Technical Field
The present invention relates to the use of 1, 3, 4-oxadiazoles and derivatives thereof as fungicides. It also relates to novel 1, 3, 4-oxadiazole derivatives, their use as fungicides and compositions comprising them.
Background
It is well known that 1, 2, 4-oxadiazole derivatives are useful as crop protection agents to combat or prevent microbial infections. For example, WO-2018/118781 and WO-2018/080859 disclose 1, 2, 4-oxadiazol-3-ylpyrimidine and 1, 2, 4-oxadiazol-3-ylpyridine derivatives that are useful for controlling microbial pests, particularly fungal pests, on plants. Fungicidally active 1, 2, 4-oxadiazoles are also known from US 2018/317490.
On the other hand, 1, 3, 4-oxadiazole derivatives are very rare and rarely used for controlling microbial pests. For example, WO-2018/165520, WO-2017/065473 and WO-2017/023133 disclose 1, 3, 4-oxadiazol-2-ylpyrimidine and 1, 3, 4-oxadiazol-2-ylpyridine derivatives which are useful as inhibitors of metalloenzymes (histone deacetylases) for the treatment of a number of human diseases.
US 2016/0157489 discloses tetrazolinone compounds comprising a pyrimidine or pyridine ring and their use for pest control.
To date, many fungicides have been developed. However, there is still a need to develop new fungicidal compounds that are effective against a broad spectrum of fungi, have lower toxicity, higher selectivity, and are used at lower dosage rates to reduce or avoid adverse environmental or toxicological effects, while still being effective against pests. It would also be desirable to have new compounds to prevent the emergence of fungicide resistance.
The present invention provides novel fungicidal compounds that are superior to known compounds and compositions in at least some of these respects.
Disclosure of Invention
The present invention also relates to the use of compounds of formula (I) as defined herein for controlling phytopathogenic fungi:
the present invention relates to compounds of formula (I) and salts, N-oxides and solvates thereof:
wherein R is1、R2、R3、m、A、W1、W2、Q1X, p and U are as described herein.
The present invention relates to a composition comprising at least one compound of formula (I) as defined herein and at least one agriculturally suitable adjuvant.
Definition of
As used herein, the term "halogen" refers to a fluorine, chlorine, bromine or iodine atom.
As used herein, the term "oxo" refers to an oxygen atom bonded to a carbon atom or a sulfur atom through a double bond.
As used herein, the term "C1-C8-alkyl "means a saturated branched or straight hydrocarbon chain having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. C1-C8Examples of-alkyl include, but are not limited to, methyl, ethyl, propyl (n-propyl), 1-methylethyl (isopropyl), butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1-dimethylethyl (tert-butyl), pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2-dimethylpropyl, 1-ethylpropyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-dimethylbutyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2-dimethylbutyl, 1-dimethylbutyl, 2, 3-dimethylbutyl, 3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1, 2-trimethylpropyl, 1, 2, 2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl. In particular, the hydrocarbon chain has 1, 2, 3 or 4 carbon atoms ("C1-C4-alkyl "), such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl or tert-butyl.
As used herein, the term "C2-C8-alkenyl "means an unsaturated branched or straight hydrocarbon chain having 2, 3, 4, 5, 6, 7 or 8 carbon atoms and comprising at least one double bond. C2-C8Examples of-alkenyl groups include, but are not limited to, vinyl (or "vinyl"), prop-2-en-1-yl (or "allyl"), prop-1-en-1-yl, but-3-enyl, but-2-enyl, but-1-enyl, pent-4-enyl, pent-3-enyl, pent-2-enyl, pent-1-enyl, hex-5-enyl, hex-4-enyl, hex-3-enyl, hex-2-enyl, hex-1-enyl, prop-1-en-2-yl (or "isopropenyl"), 2-methylprop-2-enyl, 1-methylprop-2-enyl, allyl, etc, 2-methylprop-1-enyl, 1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, 2-methylbut-2-enyl, 1-methylbut-2-enyl,3-methylbut-1-enyl, 2-methylbut-1-enyl, 1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl, 4-methylpent-4-enyl, 3-methylpent-4-enyl, 2-methylpent-4-enyl, 1-methylpent-4-enyl, 4-methylpent-3-enyl, 3-methylpent-3-enyl, 2-methylpent-3-enyl, 1-methylpent-3-enyl, 4-methylpent-2-enyl, 2-methylbut-1-enyl, 4-methylpent-1-enyl, 3-methylpent-2-enyl, 2-methylpent-2-enyl, 1-methylpent-2-enyl, 4-methylpent-1-enyl, 3-methylpent-1-enyl, 2-methylpent-1-enyl, 1-methylpent-1-enyl, 3-ethylbut-3-enyl, 2-ethylbut-3-enyl, 1-ethylbut-3-enyl, 3-ethylbut-2-enyl, 2-ethylbut-2-enyl, 1-ethylbut-2-enyl, 3-ethylbut-1-enyl, 2-ethylbut-1-enyl, 1-ethylbut-1-enyl, 2-ethylbut-1-enyl, 1-ethylbut-1-enyl, 2-Propylprop-2-enyl, 1-propylprop-2-enyl, 2-isopropylprop-2-enyl, 1-isopropylprop-2-enyl, 2-propylprop-1-enyl, 1-propylprop-1-enyl, 2-isopropylprop-1-enyl, 1-isopropylprop-1-enyl, 3-dimethylprop-1-enyl, 1- (1, 1-dimethylethyl) vinyl, but-1, 3-dienyl, pent-1, 4-dienyl, hex-1, 5-dienyl or methylhexadienyl groups.
As used herein, the term "C2-C8-alkynyl "means a branched or straight hydrocarbon chain having 2, 3, 4, 5, 6, 7 or 8 carbon atoms and comprising at least one triple bond. C2-C8Examples of-alkynyl include, but are not limited to, ethynyl, prop-1-ynyl, prop-2-ynyl (or "propargyl"), but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, prop-2-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut-2-ynyl-isopropylprop-2-ynyl, 2-dimethylbut-3-ynyl, 1-dimethylbut-2-ynyl or 3, 3-dimethylbut-1-ynyl group.
As used herein, the term "C 1-C8Haloalkyl (C)1-C8-halogenoalkyl or C1-C8-halo) "means C as defined above1-C8-alkyl groups in which one or more hydrogen atoms are substituted by one or more halogen atoms which may be the same or different. In general, C1-C8Haloalkyl contains up to 9 halogen atoms which may be the same or different.
As used herein, the term "C2-C8-haloalkenyl "means C as defined above2-C8-alkenyl groups in which one or more hydrogen atoms are replaced by one or more halogen atoms which may be the same or different. In general, C1-C8Haloalkenyl contains up to 9 halogen atoms which may be the same or different.
As used herein, the term "C2-C8-haloalkynyl "means C as defined above2-C8-alkynyl groups in which one or more hydrogen atoms are replaced by one or more halogen atoms which may be the same or different. In general, C1-C8Haloalkynyl contains up to 9 halogen atoms which may be the same or different.
As used herein, the term "C1-C8-alkoxy "means a compound of formula (C)1-C8-alkyl) -O-group, wherein the term "C1-C8-alkyl "is as defined herein. C1-C8Examples of-alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, 1-dimethylethoxy, n-pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2-dimethylpropoxy, 1-ethylpropoxy, 1-dimethylpropoxy, 1, 2-dimethylpropoxy, n-hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy Pentyloxy, 4-methylpentyloxy, 1-dimethylbutyloxy, 1, 2-dimethylbutyloxy, 1, 3-dimethylbutyloxy, 2, 2-dimethylbutyloxy, 2, 3-dimethylbutyloxy, 3-dimethylbutyloxy, 1-ethylbutoxy, 2-ethylbutoxy, 1, 2-trimethylpropoxy, 1, 2, 2-trimethylpropoxy, 1-ethyl-1-methylpropyloxy and 1-ethyl-2-methylpropyloxy.
As used herein, the term "C1-C8-haloalkoxy (C)1-C8-halogenakoxy or C1-C8-halokoxy) "means C as defined above1-C8Alkoxy groups in which one or more hydrogen atoms are replaced by one or more halogen atoms which may be the same or different. C1-C8Examples of-haloalkoxy include, but are not limited to, chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2, 2-difluoroethoxy, 2, 2, 2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2, 2-difluoroethoxy, 2, 2-dichloro-2-fluoroethoxy, 2, 2, 2-trichloroethoxy, pentafluoroethoxy and 1, 1, 1-trifluoroprop-2-oxy.
As used herein, the term "C1-C8By alkylsulfanyl (sulfanyl) is meant a compound of formula (C)1-C8-alkyl) -S-saturated linear or branched radicals, wherein the term "C" is used1-C8-alkyl "is as defined herein. C1-C8Examples of-alkylsulfanyl groups include, but are not limited to, methylsulfanyl, ethylsulfanyl, propylsulfanyl, isopropylsulfanyl, butylsulfanyl, sec-butylsulfanyl, isobutylsulfanyl, tert-butylsulfanyl, pentylsulfanyl, isopentylsulfanyl, hexylsulfanyl groups.
As used herein, the term "C1-C8By "haloalkylsulfanyl" is meant C as defined above1-C8Alkyl sulfanyl in which one or more hydrogen atoms are replaced by one or more groupsSubstituted by the same or different halogen atoms.
As used herein, the term "C1-C8-alkylsulfinyl "means a compound of formula (C)1-C8-saturated linear or branched radicals of alkyl) -S (═ O) -, where the term "C1-C8-alkyl "is as defined herein. C1-C8Examples of-alkylsulfinyl include, but are not limited to, saturated, linear or branched alkylsulfinyl groups having from 1 to 8, preferably from 1 to 6 and more preferably from 1 to 4 carbon atoms, such as, but not limited to, methylsulfinyl, ethylsulfinyl, propylsulfinyl, 1-methylethylsulfinyl, butylsulfinyl, 1-methylpropylsulfinyl, 2-methylpropylsulfinyl, 1-dimethylethylsulfinyl, pentylsulfinyl, 1-methylbutylsulfinyl, 2-methylbutylsulfinyl, 3-methylbutylsulfinyl, 2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl, 1-dimethylpropylsulfinyl, 1, 2-dimethylpropylsulfinyl, hexylsulfinyl, and the like, 1-methylpentylsulfinyl group, 2-methylpentylsulfinyl group, 3-methylpentylsulfinyl group, 4-methylpentylsulfinyl group, 1-dimethylbutylsulfinyl group, 1, 2-dimethylbutylsulfinyl group, 1, 3-dimethylbutylsulfinyl group, 2, 2-dimethylbutylsulfinyl group, 2, 3-dimethylbutylsulfinyl group, 3-dimethylbutylsulfinyl group, 1-ethylbutylsulfinyl group, 2-ethylbutylsulfinyl group, 1, 2-trimethylpropylsulfinyl group, 1, 2, 2-trimethylpropylsulfinyl group, 1-ethyl-1-methylpropylsulfinyl group and 1-ethyl-2-methylpropylsulfinyl group.
As used herein, the term "C1-C8-haloalkylsulfinyl "means C as defined above1-C8-alkylsulfinyl, in which one or more hydrogen atoms are substituted by one or more halogen atoms which may be the same or different.
As used herein, the term "C1-C8-alkylsulfonyl "means a radical of formula (C)1-C8-alkyl) -S (═ O)2A saturated linear or branched radical of (A) whereinThe term "C1-C8-alkyl "is as defined herein. C1-C8Examples of-alkylsulfonyl include, but are not limited to, methylsulfonyl, ethylsulfonyl, propylsulfonyl, 1-methylethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl, 2-methylpropylsulfonyl, 1-dimethylethylsulfonyl, pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonyl, 3-methylbutylsulfonyl, 2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, 1-dimethylpropylsulfonyl, 1, 2-dimethylpropylsulfonyl, hexylsulfonyl, 1-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentylsulfonyl, 1-dimethylbutylsulfonyl, ethylsulfonylmethyl, ethylsulfonyl, ethylsulfonylmethyl, ethylsulfonyl, ethylsulfonylmethyl, ethylsulfonyl, ethylsulfonylmethyl, ethylsulfonyl, 1, 2-dimethylbutylsulfonyl, 1, 3-dimethylbutylsulfonyl, 2, 2-dimethylbutylsulfonyl, 2, 3-dimethylbutylsulfonyl, 3-dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1, 2-trimethylpropylsulfonyl, 1, 2, 2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropylsulfonyl and 1-ethyl-2-methylpropylsulfonyl.
As used herein, the term "C1-C8-haloalkylsulfonyl "means C as defined above1-C8-alkylsulfonyl, wherein one or more hydrogen atoms are substituted by one or more halogen atoms, which may be the same or different.
As used herein, the term "C1-C8-alkylcarbonyl "means a compound of formula (C)1-C8-alkyl) -C (═ O) -saturated, linear or branched radicals, where the term "C —)1-C8-alkyl "is as defined herein.
As used herein, the term "C1-C8-haloalkylcarbonyl "means C as defined above1-C8-alkylcarbonyl, wherein one or more hydrogen atoms are substituted by one or more halogen atoms, which may be the same or different.
As used herein, the term "C1-C8-alkoxycarbonyl "means a radical of formula (C)1-C8-alkoxy radical) -C (═ O) -, saturated, linear or branched radicals, where the term "C" is used1-C8-alkoxy "is as defined herein.
As used herein, the term "C1-C8-haloalkoxycarbonyl "means C as defined above1-C8Alkoxycarbonyl, in which one or more hydrogen atoms are replaced by one or more halogen atoms, which may be the same or different.
As used herein, the term "non-aromatic C3-C12By-carbocyclic "is meant a non-aromatic saturated or unsaturated hydrocarbon ring system in which all ring members (3 to 12 different) are carbon atoms. The ring system may be monocyclic or polycyclic (fused, spiro or bridged). Non-aromatic C 3-C12Carbocyclic rings including but not limited to C3-C12Cycloalkyl (monocyclic or bicyclic), C3-C12Cycloalkenyl (monocyclic or bicyclic), comprising C fused to a monocyclic ring3-C7Bicyclic systems of aryl radicals of cycloalkyl radicals (e.g. phenyl), containing C fused to a single ring (e.g. tetrahydronaphthyl, indanyl)3-C8Bicyclic systems (e.g. indenyl, dihydronaphthyl) of aryl (e.g. phenyl) of cycloalkenyl and tricyclic systems comprising a cyclopropyl group bound via one carbon atom to a C comprising a single ring fused to a heterocycle3-C7-cycloalkyl or monocyclic C3-C8-aryl of cycloalkenyl (e.g. phenyl) linked by a bicyclic ring system. Non-aromatic C3-C12The carbocyclic ring may be attached to the parent molecular moiety through any carbon atom.
As used herein, the term "C3-C12-cycloalkyl "means a saturated monovalent monocyclic or bicyclic hydrocarbon ring containing 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms. As used herein, "C" is3-C7-cycloalkyl "denotes monocyclic C3-C7Cycloalkyl groups including, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, cycloheptyl. Bicyclic ring C6-C12Examples of-cycloalkyl include, but are not limited to, bicyclo [3.1.1]Heptane, bicyclo [2.2.1]Heptane, bicyclo [2.2.2]Octane, bicyclo [3.2.2]Nonane, bicyclo [3.3.1]Nonane, bicyclo [4.2 ].0]Octyl, octahydropentalenyl and bicyclo [4.2.1 ] ]Nonane.
As used herein, the term "C3-C12-cycloalkenyl "means an unsaturated monovalent monocyclic or bicyclic hydrocarbon ring containing 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms. Monocyclic ring C3-C8Examples of-cycloalkenyl groups include, but are not limited to, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl groups. Bicyclic ring C6-C12Examples of-cycloalkenyl groups include, but are not limited to, bicyclo [2.2.1]Hept-2-enyl or bicyclo [2.2.2]Oct-2-enyl.
As used herein, the term "aromatic C6-C14By-carbocycle "or" aryl "is meant an aromatic hydrocarbon ring system in which all ring members (6 to 14, preferably 6 to 10, not equal) are carbon atoms. The ring system may be monocyclic or fused polycyclic (e.g., bicyclic or tricyclic). Examples of aryl groups include, but are not limited to, phenyl, azulenyl, naphthyl, and fluorenyl. The aryl group may be attached to the parent molecular moiety through any carbon atom. It will also be understood that when the aryl group is substituted with one or more substituents, the one or more substituents may be located anywhere on the one or more aryl rings. In particular, where the aryl group is a phenyl group, the substituent or substituents may occupy one or two ortho, one or two meta, or para positions, or any combination of these positions.
As used herein, the term "non-aromatic 3-to 10-membered heterocyclic" or "heterocyclyl" refers to a saturated or partially unsaturated non-aromatic ring system comprising 1 to 4 or 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulfur. If the ring system contains more than one oxygen atom, they are not directly adjacent. Non-aromatic heterocycles include, but are not limited to, 3-to 7-membered monocyclic non-aromatic heterocycles and 6-to 10-membered polycyclic (e.g., bicyclic or tricyclic) non-aromatic heterocycles. The non-aromatic 3-to 10-membered heterocyclic ring may be attached to the parent molecular moiety through any carbon or nitrogen atom contained within the heterocyclic ring.
As used herein, the term "non-aromatic 3-to 7-membered monocyclic heterocycle" refers to a 3-, 4-, 5-, 6-or 7-membered monocyclic ring system containing 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein the ring system is saturated or unsaturated, but is non-aromatic. For example, the heterocyclic ring may contain one to three nitrogen atoms, or one or two oxygen atoms, or one or two sulfur atoms, or one to three nitrogen atoms and one oxygen atom, or one to three nitrogen atoms and one sulfur atom, or one sulfur atom and one oxygen atom. Examples of saturated non-aromatic heterocycles include, but are not limited to, 3-membered rings, such as oxacyclopropane (oxalanyl), aziridinyl (aziridinyl); 4-membered rings such as azetidinyl (azetidinyl), oxetanyl (oxetanyl), thietanyl (thietanyl); a 5-membered ring such as tetrahydrofuranyl, 1, 3-dioxolanyl (dioxolanyl), tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl; 6-membered rings such as piperidyl, hexahydropyridazinyl, hexahydropyrimidyl, piperazinyl, triazacyclohexyl (triazcinnanyl), hexahydrotriazinyl, tetrahydropyranyl, dioxanyl (dioxanyl), tetrahydrothiopyranyl, dithianyl (dithianyl), morpholinyl, 1, 2-oxazahexanyl (oxazinyl), oxathinyl (oxathinyl), thiomorpholinyl; or 7-membered rings such as oxacycloheptyl (oxepanyl), azepanyl (azepanyl), 1, 4-diazepanyl and 1, 4-oxaazepanyl (oxazepanyl). Examples of unsaturated non-aromatic heterocycles include, but are not limited to, 5-membered rings such as dihydrofuranyl, 1, 3-dioxolyl (dioxolyl), dihydrothienyl, pyrrolinyl, dihydroimidazolyl, dihydropyrazolyl, isoxazolinyl, dihydrooxazolyl, dihydrothiazolyl; or a 6-membered ring such as pyranyl, thiopyranyl, thiazinyl and thiadiazinyl.
As used herein, the term "non-aromatic 6-to 10-membered polycyclic heterocycle" refers to a 6-membered, 7-membered, 8-membered, 9-membered, 10-membered polycyclic (e.g., bicyclic or tricyclic) ring system containing 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein the ring system is saturated or unsaturated, but is not non-aromaticAromatic in nature. The non-aromatic bicyclic heterocycle may be fused to a monocyclic ring C3-C7-cycloalkyl, monocyclic C3-C8A monocyclic heteroaryl group as defined herein, of cycloalkenyl or a monocyclic non-aromatic heterocycle, or may consist of a monocyclic C fused to an aryl (e.g. phenyl)3-C7-cycloalkyl, monocyclic C3-C8-cycloalkenyl or a monocyclic non-aromatic heterocycle in a monocyclic non-aromatic heterocycle. When two monocyclic heterocycles containing a nitrogen atom (aromatic or nonaromatic) are fused, the nitrogen atom may be located at the bridgehead (e.g. 4, 5, 6, 7-tetrahydropyrazolo [1, 5-a ]]Pyridyl, 5, 6, 7, 8-tetrahydro- [1, 2, 4 [ ]]Triazolo [1, 5-a]Pyridyl, 5, 6, 7, 8-tetrahydroimidazo [1, 2-a ]]Pyridyl). The non-aromatic tricyclic heterocycle may consist of a monocyclic cycloalkyl group attached to the non-aromatic bicyclic heterocycle by one common atom.
As used herein, the term "aromatic 5-to 14-membered heterocyclic" or "heteroaryl" refers to an aromatic ring system comprising 1 to 4 heteroatoms independently selected from oxygen, nitrogen, and sulfur. If the ring system contains more than one oxygen atom, they are not directly adjacent. Aromatic heterocycles include aromatic 5-or 6-membered monocyclic heterocycles and 6-to 14-membered polycyclic (e.g., bicyclic or tricyclic) aromatic heterocycles. The 5-to 14-membered aromatic heterocycle may be attached to the parent molecular moiety through any carbon or nitrogen atom contained within the heterocycle.
As used herein, the term "aromatic 5-or 6-membered monocyclic heterocycle" or "monocyclic heteroaryl" refers to a 5-or 6-membered monocyclic ring system containing 1, 2, 3 or 4 heteroatoms independently selected from oxygen, nitrogen and sulfur. Examples of 5-membered monocyclic heteroaryl groups include, but are not limited to, furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl, and thiatriazolyl. Examples of 6-membered monocyclic heteroaryl groups include, but are not limited to, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl.
As used herein, the term "6-to 14-membered polycyclic aromatic heterocycle" or "polycyclic heteroaryl" refers to a 6-, 7-, 8-, 9-, 10-, 11-, 12-, 13-or 14-membered polycyclic (e.g., bicyclic or tricyclic) ring system containing 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulfur. An aromatic bicyclic heterocycle may consist of a monocyclic heteroaryl group as defined herein fused to an aryl (e.g., phenyl) or monocyclic heteroaryl group. Examples of bicyclic aromatic heterocycles include, but are not limited to, 9-membered rings such as indolyl, indolizinyl, isoindolyl, benzimidazolyl, imidazopyridinyl, indazolyl, benzotriazolyl, purinyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, and benzisoxazolyl; or a 10-membered ring, such as quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, pteridinyl (pteridinyl) and benzodioxinyl (benzodioxinyl). In a 9-or 10-membered aromatic bicyclic heterocycle comprising two fused 5-or 6-membered monocyclic aromatic heterocycles, the nitrogen atom may be located at the bridgehead (e.g., imidazo [1, 2-a ] pyridyl, [1, 2, 4] triazolo [4, 3-a ] pyridyl, imidazo [1, 2-a ] pyridyl, imidazo [2, 1-b ] oxazolyl, furo [2, 3-d ] isoxazolyl). Examples of tricyclic aromatic heterocycles include, but are not limited to, carbazolyl, acridinyl, and phenazinyl.
As used herein, the term "non-aromatic C3-C12-carbocyclic oxy "," C3-C7Cycloalkoxy and aromatic C6-C14-carbocycloxy "," aromatic 5-to 10-membered heterocyclyloxy "," non-aromatic 5-to 10-membered heterocyclyloxy "represent a group of formula-O-R, wherein R is each a non-aromatic C as defined herein3-C12-carbocyclyl, C3-C7Cycloalkyl, aromatic C6-C14-a carbocyclyl, an aromatic 5-to 14-membered heterocyclyl or a non-aromatic 5-to 14-membered heterocyclyl group.
As used herein, when a group is referred to as "substituted," the group may be substituted with one or more substituents. The expression "one or more substituents" refers to a number of substituents ranging from one to the maximum number of substituents possible based on the number of available bonding sites, provided that the conditions of stability and chemical feasibility are met.
As used herein, the term "leaving group" is understood to mean a group that is removed from a compound in a substitution or elimination reaction, such as a halogen atom, a triflate ("triflate") group, an alkoxy group, a mesylate, a p-toluenesulfonate, and the like.
When referring to the variables xxxx, the term "as described herein" is incorporated by reference into the broad definition of the variables as well as the definitions of preferred, more preferred, and even more preferred, if any.
Detailed Description
The present invention relates to the use of compounds of the formula (I) and their salts, N-oxides, solvates and optical or geometric isomers for controlling phytopathogenic fungi:
wherein
U is C containing 2 to 7 halogen atoms1-C3-haloalkyl groups, the halogen atoms being identical or different and selected from fluorine and chlorine;
Q1is O or S;
W1and W2Independently N, CH or CF;
a is selected from direct bond, O, S, S ═ O, S (═ O)2、NR4、-(C＝O)-、-(C＝S)-、-O-(C＝O)、-O-(C＝S)-、-N(R4)-(C＝O)-、-N(R4)-(C＝S)-、-(C＝O)-O-、-(C＝S)-O-、-(C＝O)-N(R5)-、-(C＝S)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-(C＝S)-N(R4)-N(R5)-、-O-N(R5)-、-N(R4)-O-、-N(R4)-N(R5)-、-O-(C＝O)-N(R5)-、-O-(C＝S)-N(R5)-、-N(R4)-(C＝O)-O-、-N(R4)-(C＝S)-O-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5)-、-O-(C＝O)-O-、-O-(C＝S)-O-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0, 1 or 2;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkenyl, C2-C8-haloalkenyl, C2-C8-alkynyl, C2-C8-haloalkynyl, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C2-C8-alkenyl and C2-C8Alkynyl may be interrupted by one or more R1aAnd R2aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C 1-C8Alkyl groups may be independently substituted by one or more R1bAnd R2bSubstituent group substitution; or
R1And R2May form C together with the carbon atom to which they are attached3-C7-cycloalkyl or a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, wherein C is3-C7Cycloalkyl and a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring may be interrupted by one or more R1bSubstituent group substitution; or
When m is 2, two consecutive R1May be formed together with the carbon atom to which they are attachedC3-C7-a cycloalkyl ring, wherein said C3-C7The cycloalkyl ring may be interrupted by one or more R1bSubstituent group substitution;
R3is hydrogen, halogen, borono (borono), (trifluoro) boryl (boryl) potassium, di- (C)1-C8-alkoxy) boryl, 1, 3, 2-dioxaborolan-2-yl (1, 3, 2-dioxaborolan-2-yl), C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C 1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein the 1, 3, 2-dioxaborolan-2-yl and 1, 3, 2-dioxaborolan-2-yl groups may be substituted by one to four C1-C3-alkyl substituents, and wherein said C is1-C8-alkyl may be substituted with one or more R3a substituents, and wherein said C is3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl may be substituted by one or more R3bSubstituent group substitution;
R4and R5Independently selected from hydrogen atom, hydroxyl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C2-C8-alkenyl, C2-C8-haloalkenyl, C3-C8-alkynyl, C3-C8-haloalkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, formyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, arylcarbonyl, C1-C8Alkoxycarbonyl, C1-C8-haloalkoxycarbonyl, C1-C8-alkylsulfonyl, C1-C8Haloalkylsulfonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C 2-C8-alkenyl, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8Alkoxycarbonyl and C1-C8The alkylsulfonyl radicals may be independently substituted by one or more R4aAnd R5aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, arylcarbonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8The alkyl and phenylsulfonyl groups may each be substituted by one or more R4bAnd R5bSubstituent group substitution;
R1a、R2a、R3a、R4aand R5aIndependently selected from halogen, nitro, hydroxy, cyano, carboxy, amino, sulfanyl, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C 1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
R1b、R2b、R3b、R4band R5bIndependently selected from halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group, amino group, sulfanyl group, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8Haloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C 1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
with the proviso that the compound of formula (I) is not:
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6],
-2-isopropyl-5, 6-bis-methyl-3- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } pyridin-4-ol [2133324-02-2 ].
Compounds resulting from combinations that violate natural laws and are therefore excluded by the skilled person based on his/her expert knowledge are not included herein. For example, ring structures having three or more adjacent oxygen atoms are excluded.
According to the invention, the compounds of the formula (I) can be used for controlling phytopathogenic fungi of plants, parts of plants, seeds, fruits or of the soil in which the plants are growing. Preferably, the phytopathogenic fungus is selected from Puccinia species (Puccinia species), such as Puccinia recondita (Puccinia recondita), Puccinia graminis (Puccinia graminis) or Puccinia striiformis (Puccinia striiformis); monospora species (Uromyces species), such as, for example, Puccinia verrucosa (Uromyces apendiculus); and rust pathogens, particularly selected from the genera Acidovorax (Gymnosphaera species), such as, for example, Puccinia fusca (Gymnosphaera sabinaea); camellia sinensis species (Hemileia species), such as, for example, Camellia caffeofaciens (Hemileia vastatrix), and Hymenochaetaceae species (Phakopsora species), such as, for example, Phakopsora pachyrhizi (Phakopsora pachyrhizi) or Phakopsora javanica (Phakopsora meibomiae). Particularly preferred are rust pathogens, in particular phakopsora pachyrhizi and phakopsora pomonensis.
The compound of formula (I) may suitably be in its free form, salt form, N-oxide form or solvate form (e.g. hydrate).
Depending on the nature of the substituents, the compounds of formula (I) may exist in different stereoisomeric forms. These stereoisomers are, for example, enantiomers, diastereomers, atropisomers or geometric isomers. Thus, the present invention includes both pure stereoisomers and any mixture of such isomers. When a compound may exist in two or more tautomeric forms in equilibrium, reference to the compound by a description of one tautomer should be taken to include all tautomeric forms.
Any of the compounds of the present invention may also exist in one or more geometric isomeric forms, depending on the number of double bonds in the compound. Geometric isomers based on the nature of the double bond or ring substituents may exist in either the cis (═ Z-) or trans (═ E-) form. The invention therefore likewise relates to all geometric isomers and all possible mixtures in all proportions.
Depending on the nature of the substituents, the compounds of formula (I) may be present as the free compounds and/or as salts thereof (e.g. agrochemically active salts).
Agrochemically active salts include acid addition salts of inorganic and organic acids as well as salts of conventional bases. Examples of the inorganic acid are hydrohalic acids (e.g., hydrogen fluoride, hydrogen chloride, hydrogen bromide, and hydrogen iodide), sulfuric acid, phosphoric acid, and nitric acid, and acidic salts such as sodium hydrogen sulfate and potassium hydrogen sulfate. Useful organic acids include, for example, formic acid, carbonic acid and alkanoic acids (e.g. acetic acid, trifluoroacetic acid, trichloroacetic acid and propionic acid), and also glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, saturated or monounsaturated or diunsaturated fatty acids having from 6 to 20 carbon atoms, alkylsulfuric monoesters, alkylsulfonic acids (sulfonic acids having a linear or branched alkyl group having from 1 to 20 carbon atoms), arylsulfonic acids or arylsulfonic acids (aromatic groups, for example phenyl and naphthyl, which carry one or two sulfonic acid groups), alkylphosphonic acids (phosphonic acids having a linear or branched alkyl group having from 1 to 20 carbon atoms), arylphosphonic acids or aryldiphosphonic acids (aromatic groups, for example phenyl and naphthyl, which carry one or two phosphonic acid groups), where the alkyl and aryl groups may also carry substituents, such as p-toluenesulfonic acid, salicylic acid, p-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid, and the like.
Solvates of the compounds of the invention or salts thereof are stoichiometric compositions of the compound and the solvent.
The compounds of the present invention may exist in a variety of crystalline and/or amorphous forms. Crystalline forms include unsolvated crystalline forms, solvates, and hydrates.
The compounds of formula (I) are referred to herein as "one or more active ingredients".
In the above formula (I), U is preferably C containing 2 to 3 halogen atoms1-haloalkyl groups, the halogen atoms being identical or different and chosen from fluorine and chlorine. More preferably, U is selected from CHF2、CClF2And CF3Still more preferably, U is CHF2Or CF3Even more preferably, U is CHF2。
In some embodiments, in formula (I) above, Q1Preference is given toIs O.
In the above formula (I), W1Preferably N or CH.
In the above formula (I), W2Preferably N or CH.
In some embodiments of formula (I) above, W1And W2Is N, or W1Is N and W2Is CH, more preferably, W1And W2Is N.
In the above formula (I), A is preferably a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-。
In some embodiments, a is a direct bond, O, NR4、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5) More preferably O, NH, - (C ═ O) -O-, - (C ═ O) -NH-, or- (C ═ O) -NMe-, even more preferably O or NH.
In some embodiments, in formula (I) above, A is NR4NH is preferred.
In some embodiments, in formula (I) above, a is O.
In some embodiments, in formula (I) above, m is preferably 0 or 1, more preferably m is 1.
In the above formula (I), p is preferably 0 or 1, more preferably p is 0.
In the above formula (I), each R1And each R2Preferably independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7-cycloalkyl and aryl, wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring.
In the above formula (I), R is more preferred1Selected from the group consisting of hydrogen, fluoro, chloro, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl, and
R2selected from the group consisting of hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl and difluoromethyl,
Or
R1And R2May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring, or
When m is 2, two consecutive R1May form, together with the carbon atom to which they are attached, a cyclopropyl, cyclobutyl or cyclopentyl ring.
In the above formula (I), even more preferred
m is 1, m is a linear chain,
R1selected from the group consisting of hydrogen, methyl, ethyl, trifluoromethyl, ethynyl and cyclopropyl, and
R2is a hydrogen atom, and is,
or
R1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl or oxetanyl ring, more preferably a cyclopropyl or cyclobutyl ring, and most preferably a cyclopropyl ring.
In some embodiments, in formula (I) above, at least [ CR ] is present1R2]Group, wherein R1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring,
wherein if m is 2, the other [ CR1R2]R of the radical1And R2Independently selected from hydrogen, fluorine, chlorine, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butylA group selected from the group consisting of hydroxy methyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl, or together with the carbon atoms to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring.
In some embodiments, in formula (I) above, m is 1, and R is1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring, more preferably a cyclopropyl, cyclobutyl or oxetanyl ring.
In some preferred embodiments, m is 1, and R is1And R2Together with the carbon atom to which they are attached form a cyclopropyl or cyclobutyl ring, preferably a cyclopropyl ring.
In some other preferred embodiments, m is 1, and R is1And R2Together with the carbon atom to which they are attached form an oxetanyl ring.
In still other preferred embodiments of the present invention,
m is 1, m is a linear chain,
R1selected from the group consisting of hydrogen, methyl, ethyl, trifluoromethyl and cyclopropyl, and
R2is hydrogen.
In the above formula (I), R3Preferably selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy, wherein the 1, 3, 2-dioxaborolan-2-yl radical may be substituted by one to four C1-C3-alkyl substituent substituted, wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C 1-C8-haloalkoxy substituents, and wherein said C is3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl andaryloxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group.
In the above formula (I), R3More preferably from hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and naphthyl; a heterocyclyl group selected from the group consisting of tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazacyclohexanyl, oxathiahexidinyl, thiomorpholinyl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, and isoquinolinyl; biphenyl, phenoxyphenyl and phenoxy;
And wherein said C3-C7-cycloalkyl, C3-C8Cycloalkenyl, arylHeterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted with one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
In some preferred embodiments, R3Selected from aryl and heteroaryl. In these embodiments, it is preferred that aryl is selected from phenyl and naphthyl; heteroaryl is selected from the group consisting of furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, and isoquinolinyl; and aryl and heteroaryl groups may be substituted with one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
In some embodiments, R3Selected from phenyl and pyridine, wherein phenyl and pyridine may be substituted with one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl. In these embodiments, R3More preferably phenyl, which is unsubstituted or substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropylAlkyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl, preferably unsubstituted or substituted with one or two substituents independently selected from fluoro, chloro, bromo, methyl and methoxy.
In the above formula (I), R4And R5Preferably independently selected from hydrogen, hydroxy, C 1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted with one or two fluorine atoms.
In the above formula (I), R4And R5More preferably independently selected from hydrogen, hydroxy, C1-C4Alkyl radical, C1-C4-haloalkyl group, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C4-alkynyl, C1-C4-alkylcarbonyl group, C1-C4-haloalkylcarbonyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted by one or two fluorine atoms.
In the above formula (I), R4And R5Most preferably independently selected from hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-difluoroethyl, methoxy, ethoxy, prop-2-ynyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted with one or two fluorine atoms.
In some particularly preferred embodiments, R4And R5Is hydrogen.
The preferences mentioned above with respect to the substituents of the compounds of the invention can be combined in various ways. Thus, the combination of these preferred features provides a subclass of compounds of the present invention. Examples of such subclasses of preferred compounds of the invention are:
preferred features of-UAnd Q1、W1、W2、A、p、m、R1、R2、R3、R4And R5One or more preferred features of (a);
-Q1Preferred features of (2) and U, W1、W2、A、p、m、R1、R2、R3、R4And R5One or more preferred features of (a);
-W1preferred features of (2) and U, Q1、W2、A、p、m、R1、R2、R3、R4And R5One or more preferred features of (a);
-W2preferred features of (2) and U, Q1、W1、A、p、m、R1、R2、R3、R4And R5One or more preferred features of (a);
preferred features of A with U, Q1、W1、W2、p、m、R1、R2、R3、R4And R5One or more preferred features of (a);
preferred features of p with U, Q1、W1、W2、A、m、R1、R2、R3、R4And R5One or more preferred features of (a);
preferred features of m with U, Q1、W1、W2、A、p、R1、R2、R3、R4And R5One or more preferred features of (a);
-R1preferred features of (2) and U, Q1、W1、W2、A、p、m、R2、R3、R4And R5One or more preferred features of (a);
-R2preferred features of (2) and U, Q1、W1、W2、A、p、m、R1、R3、R4And R5One or more preferred features of (a);
-R3preferred features ofU、Q1、W1、W2、A、p、m、R1、R2、R4And R5One or more preferred features of (a);
-R4preferred features of (2) and U, Q1、W1、W2、A、p、m、R1、R2、R3And R5One or more preferred features of (a);
-R5preferred features of (2) and U, Q1、W1、W2、A、p、m、R1、R2、R3And R4One or more preferred features of (a);
in these combinations of preferred features of substituents of the compounds of the invention, said preferred features may also be selected from U, Q1、W1、W2、A、p、m、R1、R2、R3、R4And R5Each of the more preferred features to form the most preferred subclass of compounds of the invention.
Preference is given to the use of compounds of the formula (I) and their salts, N-oxides, solvates and optical or geometric isomers:
wherein
U is selected from CHF2、CClF2And CF 3；
Q1Is O or S;
W1and W2Independently is N or CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0 or 1;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7Cycloalkyl and aryl, preferably hydrogen, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl and C3-C7-cycloalkyl, wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring;
R3selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy,
wherein the 1, 3, 2-dioxaborolan-2-yl may be substituted by one to four C1-C3-an alkyl substituent, and (C) a substituted alkyl group,
wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C 1-C8-a haloalkoxy substituent, and
wherein said C3-C7-cycloalkyl, C3-C8The cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selectedFrom halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group;
R4and R5Independently selected from hydrogen, hydroxy, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted by one or two fluorine atoms;
with the proviso that the compound of formula (I) is not:
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6 ].
Particular preference is given to the use of compounds of the formula (I) and their salts, N-oxides, solvates and optical or geometric isomers, in which
U is selected from CHF2、CClF2And CF 3Especially CHF2Or CF3；
Q1Is O or S, preferably O;
W1and W2Independently is N or CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The radicals may be identical or differentThe same is carried out;
p is 0;
R1selected from the group consisting of hydrogen, fluoro, chloro, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl,
or when m is 2, two consecutive R1May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl or cyclopentyl ring, and
R2selected from the group consisting of hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl and difluoromethyl,
or
R1And R2May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring;
R3selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c 3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and naphthyl; a heterocyclyl group selected from the group consisting of tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazacyclohexanyl, oxathiahexidinyl, thiomorpholinyl, and 1, 3-dihydro-2H-isoindol-2-yl; a heteroaryl group selected from furyl (furyl), thienyl, pyrrolyl, pyrazolyl, and pharmaceutically acceptable salts thereof,Imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl and isoquinolinyl; biphenyl, phenoxyphenyl and phenoxy;
and wherein said C 3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl;
preferably, R3Selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and 2-naphthyl; a heterocyclyl group selected from piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, morpholin-4-yl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of 2-furyl (furyl) (2-furyl), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, IH-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, and quinolin-2-yl; biphenyl, phenoxyphenyl and phenoxy;
And wherein said C3-C7-cycloalkyl, C3-C8-RingAlkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, and phenoxy groups can be substituted with one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl;
R4and R5Independently selected from hydrogen, hydroxy, C1-C4Alkyl radical, C1-C4-haloalkyl group, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C4-alkynyl, C1-C4-alkylcarbonyl group, C1-C4-haloalkylcarbonyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted by one or two fluorine atoms, preferably R4And R5Independently selected from hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-difluoroethyl, methoxy, ethoxy, prop-2-ynyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted with one or two fluorine atoms;
with the proviso that the compound of formula (I) is not:
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6 ].
In some embodiments of a particularly preferred use of the compounds of formula (I) as defined above, U is CHF2。
In some embodiments of a particularly preferred use of the compounds of formula (I) as defined above, W is1And W2Is N, or W1Is N and W2Is CH, preferably W1And W2Is N.
In some embodiments of a particularly preferred use of the compounds of formula (I) as defined above, a is a direct bond, O, S、NR4、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5) -, more preferably O, S or NR4Even more preferably O or NR4Most preferably NH.
In some embodiments of a particularly preferred use of the compounds of formula (I) as defined above,
R1selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, vinyl, ethynyl, phenyl and cyclopropyl,
R2is a hydrogen atom, and is,
or
R1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl or oxetanyl ring, more preferably a cyclopropyl or cyclobutyl ring, and most preferably a cyclopropyl ring.
In some embodiments of a particularly preferred use of the compounds of formula (I) as defined above, R3Is selected from C3-C7-cycloalkyl, C 3-C8Cycloalkenyl, aryl, heterocyclyl and heteroaryl, preferably C3-C7-cycloalkyl, aryl, heterocyclyl and heteroaryl; more preferably aryl or heteroaryl, and most preferably aryl;
wherein C is3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;
wherein C is3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl;
wherein aryl is selected from phenyl and naphthyl;
wherein the heterocyclyl group is selected from the group consisting of tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazacyclohexanyl, oxathiahexanyl, thiomorpholinyl and 1, 3-dihydro-2H-isoindol-2-yl, preferably from the group consisting of piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothiapyranyl, dithianyl, thiomorpholinyl and 1, 3-2H-isoindol-2-yl, Morpholin-4-yl and 1, 3-dihydro-2H-isoindol-2-yl;
wherein heteroaryl is selected from the group consisting of furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl and isoquinolinyl, preferably selected from the group consisting of 2-furyl (2-furyl), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl and quinolin-2-yl;
And wherein said C3-C7-cycloalkyl, C3-C8-the cycloalkenyl, aryl, heterocyclyl and heteroaryl groups may be substituted with one to three substituents independently selected from: fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl. In some such embodiments, R3Selected from phenyl and pyridyl, wherein said phenyl and pyridyl may be substituted with one to three substituents independently selected from the group consisting of: fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl. In these embodiments, R3More preferably phenyl, which is unsubstituted or substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl Phenyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl, especially unsubstituted phenyl or phenyl substituted with one or two substituents independently selected from fluoro, chloro, bromo, methyl and methoxy.
In some embodiments of a particularly preferred use of the compounds of formula (I) as defined above, R4And R5Is hydrogen.
In some embodiments of a particularly preferred use of the compounds of formula (I) as defined above,
u is CHF2Or CF3；
p is 0;
W1and W2Is N; and is
A is O or NR4。
In some embodiments of the use of the invention, in formula (I), the substituents are defined as follows:
u is CHF2Or CF3；
Q1Is O;
p is 0;
W1and W2Is N;
a is O or NH;
m is 1;
R1selected from hydrogen, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C2-C8-alkenyl, C3-C7-a cycloalkyl group and a phenyl group,
R2is a hydrogen atom, and is,
or
R1And R2Together with the carbon atom to which they are attached form C3-C7-a cycloalkyl or oxetanyl ring; and is
R3Is selected from C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl and heteroaryl groups,
wherein C is3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;
Wherein C is3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl;
wherein aryl is selected from phenyl and naphthyl;
wherein heterocyclyl is selected from piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, morpholin-4-yl, and 1, 3-dihydro-2H-isoindol-2-yl;
wherein heteroaryl is selected from 2-furyl (furyl) (2-furyl), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl and quinolin-2-yl;
and wherein said C3-C7-cycloalkyl, C3-C8-the cycloalkenyl, aryl, heterocyclyl and heteroaryl groups may be substituted with one to three substituents independently selected from: fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl. In said embodiment, R is more preferred 1Selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, vinyl, ethynyl, phenyl and cyclopropyl, and
R2is a hydrogen atom, and is,
or
R1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl or oxetanyl ring, more preferably a cyclopropyl or cyclobutyl ring, and most preferably a cyclopropyl ring.
In some of these embodiments, m is 1, and R is1And R2Together with the carbon atom to which they are attached form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexylOr an oxetanyl ring, more preferably a cyclopropyl, cyclobutyl or oxetanyl ring.
In some of these embodiments, m is 1, and R is1And R2Together with the carbon atom to which they are attached form a cyclopropyl or cyclobutyl ring, preferably a cyclopropyl ring.
In some of these embodiments, m is 1, and R is1And R2Together with the carbon atom to which they are attached form an oxetanyl ring.
In some of these embodiments, the first and second electrodes are,
m is 1, m is a linear chain,
R1selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, vinyl, ethynyl, phenyl and cyclopropyl, and
R2is hydrogen.
In some embodiments of the use of the invention, the substituents are defined as follows:
U is CHF2Or CF3；
Q1Is O;
p is 0;
W1and W2Is N;
a is O or NH;
m is 1;
R1selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, vinyl, ethynyl, phenyl and cyclopropyl, and
R2is a hydrogen atom, and is,
or
R1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl or oxetanyl ring; and is
R3Selected from phenyl and pyridine, wherein said phenyl and pyridine may be substituted with one to three substituents independently selected from the group consisting of: fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoroMethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
Most preferably a compound of formula (I) selected from the following and their salts, N-oxides, solvates and optical or geometric isomers:
i.0014- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid
0022- (difluoromethyl) -5- [4- (methylsulfanyl) phenyl ] -1, 3, 4-oxadiazole
0034- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid methyl ester
0044- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid
0052- (difluoromethyl) -5- [4- (1H-1, 2, 3-triazol-1-yl) phenyl ] -1, 3, 4-oxadiazole
0064- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid methyl ester
0072- ([ biphenyl ] -4-yl) -5- (difluoromethyl) -1, 3, 4-oxadiazole
I.0084- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzoic acid
0092- (4-bromophenyl) -5- (difluoromethyl) -1, 3, 4-oxadiazole
0102- (difluoromethyl) -5- [4- (1H-imidazol-1-ylmethyl) phenyl ] -1, 3, 4-oxadiazole
0114- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzoic acid methyl ester
012N- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } -2, 2-difluoroacetamide
013N- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } pyrimidin-2-amine
0142- ([ biphenyl ] -4-yl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole
0155- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } -3-ethyl-1, 2, 4-oxadiazol
0164- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methoxyethyl) benzamide
017N- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } -2-fluoroaniline
0183-Ethyl-5- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } -1, 2, 4-oxadiazol
I.0192, 2' - (1, 4-phenylene) bis [5- (difluoromethyl) -1, 3, 4-oxadiazole ]
020N- (2-methoxyethyl) -4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzamide
0212- (difluoromethyl) -5- [4- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl ] -1, 3, 4-oxadiazole
0224- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methyl-N-phenylbenzamide
023N- (2-methoxyethyl) -4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzamide
0242- {4- [ (4-chlorophenoxy) methyl ] phenyl } -5- (difluoromethyl) -1, 3, 4-oxadiazole
0254- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-fluorophenyl) cyclopropyl ] aniline
026N-methyl-N-phenyl-4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzamide
0274- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2, 4-difluorophenyl) benzamide
028N- (2, 4-difluorophenyl) -4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzamide
029N- (2, 4-difluorophenyl) -4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzamide
0305- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-amine
I.0312-chloro-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine
0325- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine-2-carboxylic acid
0335- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methylpyridine-2-carboxamide
034N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } acetamide
0355- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-furanyl) pyridine
0365- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (1H-pyrazol-1-yl) pyridine
0375- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (trifluoromethyl) pyridine
I.038 {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } carbamic acid methyl ester
0395- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (prop-2-yn-1-yl) pyridine-2-carboxamide
0405- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (piperidin-1-yl) pyridine
0414- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } morpholine
0425- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N ', N' -dimethylpyridine-2-carbohydrazide
0435- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-phenoxypyridine
0445- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-methylcyclopropyl) pyridine-2-carboxamide
045N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -1-methylcyclopropanecarboxamide
046N- (cyclopropylmethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine-2-carboxamide
0475- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methoxyethyl) pyridine-2-carboxamide
0485- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (4-methylphenyl) pyridine-2-carboxamide
0495- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methyl-N-phenylpyridine-2-carboxamide
050N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -2-phenylacetamide
0511- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -3-phenylurea
0525- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (4-fluorophenyl) ethyl ] pyridin-2-amine
0535- {5- [ chloro (difluoro) methyl ] -1, 3, 4-oxadiazol-2-yl } -N- (2-fluorophenyl) pyridin-2-amine
0545- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (4-fluorophenyl) cyclopropyl ] pyridin-2-amine
055N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -2, 4-difluorobenzamide
0565- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1-phenylcyclopropyl) methyl ] pyridine-2-carboxamide
0575- {5- [ chloro (difluoro) methyl ] -1, 3, 4-oxadiazol-2-yl } -N- [1- (2-fluorophenyl) cyclopropyl ] pyridin-2-amine
0584- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } piperazine-1-carboxylic acid tert-butyl ester
0595- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
0605- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methylpyrimidin-2-amine
0612-chloro-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0625- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N, N-dimethylpyrimidin-2-amine
0635- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (prop-2-yn-1-yl) pyrimidin-2-amine
0645- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2, 2-dimethylhydrazino) pyrimidine
0652- (Cyclopent-1-en-1-yl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0665- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-methylcyclopropyl) pyrimidin-2-amine
067N- (cyclopropylmethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
0685- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methoxyethyl) pyrimidin-2-amine
0695- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-phenylpyrimidine
0705- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (pyridin-3-yl) pyrimidine
0715- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-thienyl) pyrimidine
0725- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (3-thienyl) pyrimidine
073N- [ (1RS) -1-cyclopropylethyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
0744- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } morpholine
I.0752-benzyl-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0765- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-phenylpyrimidin-2-amine
0775- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (4-fluorophenyl) pyrimidine
0785- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (1-ethyl-1H-pyrazol-5-yl) pyrimidine
0795- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-fluoropyridin-4-yl) pyrimidine
0805- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (6-fluoropyridin-3-yl) pyrimidine
0815- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (3, 5-dimethyl-1, 2-oxazol-4-yl) pyrimidine
082N- [ [1, 1' -bis (cyclopropyl) ] -1-yl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
0832- (cyclohexylmethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
084N- (2-cyclopropylpropan-2-yl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
0854- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } benzonitrile
0865- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methylphenyl) pyrimidin-2-amine
0875- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methyl-N-phenylpyrimidin-2-amine
088N-benzyl-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
0895- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (4-methoxyphenyl) pyrimidine
0902- (benzyloxy) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0915- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (4-fluorobenzyl) pyrimidine
0925- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (phenylsulfanyl) pyrimidine
0935- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-fluorophenyl) pyrimidin-2-amine
0945- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (3-fluorophenyl) pyrimidin-2-amine
0955- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (4-fluorophenyl) pyrimidin-2-amine
0965- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-ethyl-1H-pyrazol-5-yl) pyrimidin-2-amine
0975- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1 '-methyl [1, 1' -bis (cyclopropyl) ] -1-yl ] pyrimidin-2-amine
0985- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (4-fluorophenoxy) pyrimidine
0992- (2-chlorophenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
1002- (3-chlorophenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
1012- (4-chlorophenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
1022- (2-Chloropyridin-4-yl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
1032- (5-Chloropyridin-3-yl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
I.1041- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) cyclopropanecarboxylic acid methyl ester
1055- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (tetrahydro-2H-pyran-4-ylmethyl) pyrimidin-2-amine
1062- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } isoindoline (isoindonoline)
1075- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-methoxybenzyl) pyrimidine
1085- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-methyl-2-phenylhydrazino) pyrimidine
1095- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methoxyphenyl) pyrimidin-2-amine
110N-benzyl-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-hydroxypyrimidin-2-amine
1115- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-fluorobenzyl) pyrimidin-2-amine
1125- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (4-fluorobenzyl) pyrimidin-2-amine
I.1135- [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl ] -N- (2-fluorophenyl) pyrimidin-2-amine
I.114N- (2-chlorophenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1152- (2, 4-difluorobenzyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
I.116N- (2-fluorophenyl) -5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1171- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) cyclopropanecarboxylic acid ethyl ester
1185- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1-phenylprop-2-yn-1-yl ] pyrimidin-2-amine
119N- (2-Cyclopropylphenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1205- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- [ (1-phenylcyclopropyl) oxy ] pyrimidine
1215- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (pyridin-2-yl) cyclopropyl ] pyrimidin-2-amine
1225- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1-phenylpropyl ] pyrimidin-2-amine
1235- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [ (1RS) -1-phenylethyl ] sulfanyl } pyrimidine
1245- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (2-fluorophenyl) ethyl ] pyrimidin-2-amine
1255- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (4-fluorophenyl) ethyl ] pyrimidin-2-amine
125a 5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1R) -1- (4-fluorophenyl) ethyl ] pyrimidin-2-amine
125b 5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1s) -1- (4-fluorophenyl) ethyl ] pyrimidin-2-amine
126N- (1-Cyclohexylcyclopropyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1275- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [ (1RS) -1- (4-fluorophenyl) ethyl ] oxy } pyrimidine
128N- (2-chlorobenzyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
129N- (2, 6-difluorobenzyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
130N- (2-fluorophenyl) -5- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] pyrimidin-2-amine
1315- {5- [ chloro (difluoro) methyl ] -1, 3, 4-oxadiazol-2-yl } -N- (2-fluorophenyl) pyrimidin-2-amine
1325- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-methylphenyl) cyclopropyl ] pyrimidin-2-amine
1335- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (4-methylphenyl) cyclopropyl ] pyrimidin-2-amine
1345- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-phenylcyclobutyl) pyrimidin-2-amine
1355- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1-phenylcyclopropyl) methyl ] pyrimidin-2-amine
136N- [ (RS) -cyclopropyl (phenyl) methyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1375- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (pyridin-2-yl) cyclobutyl ] pyrimidin-2-amine
1385- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-phenylbut-2-yl) pyrimidin-2-amine
1395- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -2-methyl-1-phenylpropyl ] pyrimidin-2-amine
1405- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1-phenylbutyl ] pyrimidin-2-amine
141 (2RS) - ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) (4-fluorophenyl) acetonitrile
I.1425- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- [ (3-phenyloxetan-3-yl) oxy ] pyrimidine
1435- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [3- (pyridin-2-yl) oxetan-3-yl ] oxy } pyrimidine
1445- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-fluorophenyl) cyclopropyl ] pyrimidin-2-amine
1455- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (3-fluorophenyl) cyclopropyl ] pyrimidin-2-amine
1465- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (4-fluorophenyl) cyclopropyl ] pyrimidin-2-amine
147N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -O-methyl-N- [ (1RS) -1-phenylethyl ] hydroxylamine
I.148N-benzyl-N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -O-ethylhydroxylamine
1495- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [1- (4-fluorophenyl) cyclopropyl ] oxy } pyrimidine
1505- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (4-fluorophenyl) propan-2-yl ] pyrimidin-2-amine
1515- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (2, 6-difluorophenyl) ethyl ] pyrimidin-2-amine
1524- [1- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) cyclopropyl ] benzonitrile
1535- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-phenylcyclopentyl) pyrimidin-2-amine
1555- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-methoxyphenyl) cyclopropyl ] pyrimidin-2-amine
1565- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (3-methoxyphenyl) cyclopropyl ] pyrimidin-2-amine
1575- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (4-methoxyphenyl) cyclopropyl ] pyrimidin-2-amine
1585- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [3- (4-methylphenyl) oxetan-3-yl ] pyrimidin-2-amine
1595- [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl ] -N- (1-phenylcyclobutyl) pyrimidin-2-amine
160N- (1-phenylcyclobutyl) -5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
I.161N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -N- (2-methoxybenzyl) -O-methylhydroxylamine
1625- [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl ] -N- [1- (2-fluorophenyl) cyclopropyl ] pyrimidin-2-amine
163N- [1- (2-chlorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1645- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2, 6-difluorophenyl) cyclopropyl ] pyrimidin-2-amine
165N- [1- (2-fluorophenyl) cyclopropyl ] -5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
166N- ([ biphenyl ] -2-yl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1675- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [1- (2, 6-difluorophenyl) cyclopropyl ] oxy } pyrimidine
1685- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (2, 6-difluorophenyl) propan-2-yl ] pyrimidin-2-amine
I.169N- (4-chlorobenzyl) -N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -O-methylhydroxylamine
1705- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1 '-phenyl [1, 1' -bis (cyclopropyl) ] -1-yl ] pyrimidin-2-amine
1715- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-fluorophenyl) cyclopentyl ] pyrimidin-2-amine
1725- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (3-fluorophenyl) cyclopentyl ] pyrimidin-2-amine
173N- (1-phenylcyclobutyl) -5- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] pyrimidin-2-amine
174N- [1- (2-chlorophenyl) cyclobutyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
I.175N- [1- (3-chlorophenyl) cyclobutyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1765- {5- [ chloro (difluoro) methyl ] -1, 3, 4-oxadiazol-2-yl } -N- (1-phenylcyclobutyl) pyrimidin-2-amine
1775- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2, 6-difluorophenyl) cyclobutyl ] pyrimidin-2-amine
I.178N- [1- (2-fluorophenyl) cyclopropyl ] -5- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] pyrimidin-2-amine
1795- {5- [ chloro (difluoro) methyl ] -1, 3, 4-oxadiazol-2-yl } -N- [1- (2-fluorophenyl) cyclopropyl ] pyrimidin-2-amine
1804- [1- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) cyclopropyl ] benzoic acid methyl ester
1815- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -2, 2, 2-trifluoro-1- (4-fluorophenyl) ethyl ] pyrimidin-2-amine
182N- [1- (4-chlorophenyl) cyclohexyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
183N- [1- (2-bromophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
184N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -O-methyl-N- { (1RS) -1- [3- (trifluoromethyl) phenyl ] ethyl } hydroxylamine
185N- (2, 4-difluorobenzoyl) -N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -2, 4-difluorobenzamide
1865- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (1-methylcyclopropyl) ethyl ] pyrimidin-2-amine
1875- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-isopropylcyclopropyl) pyrimidin-2-amine
1885- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (pyridin-3-yl) ethyl ] pyrimidin-2-amine
1895- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (pyridin-2-yl) ethyl ] pyrimidin-2-amine
1905- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (pyridin-4-yl) ethyl ] pyrimidin-2-amine
1915- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (pyrimidin-2-yl) ethyl ] pyrimidin-2-amine
1925- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (2-thienyl) ethyl ] pyrimidin-2-amine
193N- [ (1RS) -1-cyclohexylethyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1945- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (1, 3-thiazol-4-yl) ethyl ] pyrimidin-2-amine
1955- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-phenylcyclopropyl) pyrimidin-2-amine
1965- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ rac- (1R, 2S) -2-phenylcyclopropyl ] pyrimidin-2-amine
1975- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-phenylprop-2-yl) pyrimidin-2-amine
1985- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (pyridin-2-yl) propan-2-yl ] pyrimidin-2-amine
1995- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (pyridin-3-yl) propan-2-yl ] pyrimidin-2-amine
2005- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (4-fluorophenyl) ethyl ] pyrimidin-2-amine
1.201N- (1-benzylcyclopropyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2025- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (3-methylphenyl) cyclopropyl ] pyrimidin-2-amine
2035- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (4-methylpyridin-2-yl) cyclopropyl ] pyrimidin-2-amine
2045- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (4-methylphenyl) propan-2-yl ] pyrimidin-2-amine
2055- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (2-methylphenyl) propan-2-yl ] pyrimidin-2-amine
2065- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ rac- (1R, 2R) -2- (4-fluorophenyl) cyclopropyl ] pyrimidin-2-amine
2075- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (4-methoxyphenyl) ethyl ] pyrimidin-2-amine
2085- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-furanyl) cyclopentyl ] pyrimidin-2-amine
2095- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (2-methoxyphenyl) ethyl ] pyrimidin-2-amine
2105- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (2RS) -1- (4-fluorophenyl) propan-2-yl ] pyrimidin-2-amine
2115- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (2RS) -2- (4-fluorophenyl) propyl ] pyrimidin-2-amine
2125- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (2-fluorophenyl) propan-2-yl ] pyrimidin-2-amine
213N- [ (1RS) -1- (3-chlorophenyl) ethyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
214N- [ (1RS) -1- (6-Chloropyridin-3-yl) ethyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2155- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (2, 4-difluorophenyl) ethyl ] pyrimidin-2-amine
2165- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2, 6-dimethylphenyl) cyclopropyl ] pyrimidin-2-amine
2175- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -2-phenylcyclopentyl ] pyrimidin-2-amine
2185- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (pyridin-3-yl) cyclopentyl ] pyrimidin-2-amine
2195- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (pyridin-2-yl) cyclopentyl ] pyrimidin-2-amine
2205- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (4-fluorophenyl) cyclobutyl ] pyrimidin-2-amine
2215- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-fluorophenyl) cyclopropyl ] -N-methylpyrimidin-2-amine
222 ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) (pyridin-2-yl) acetic acid methyl ester
2235- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (4-fluorophenyl) -2-methylpropan-2-yl ] pyrimidin-2-amine
2245- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [2- (4-fluorophenyl) -2-methylpropyl ] pyrimidin-2-amine
2255- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-thienyl) cyclopentyl ] pyrimidin-2-amine
226N- [1- (4-chlorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
227N- [1- (3-chlorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
I.228N- [1- (4-Chloropyridin-2-yl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2295- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (3, 4-difluorophenyl) cyclopropyl ] pyrimidin-2-amine
230N- [ (1RS) -1- (4-chlorophenyl) propyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
231N- [2- (4-chlorophenyl) propan-2-yl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2325- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (2-naphthyl) ethyl ] pyrimidin-2-amine
2335- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (quinolin-2-yl) ethyl ] pyrimidin-2-amine
234N- [2, 2-difluoro-2- (4-fluorophenyl) ethyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
235- (2RS) -2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) -2- (3, 4-dimethylphenyl) propan-1-ol
2365- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-fluoro-3-methoxyphenyl) cyclopropyl ] pyrimidin-2-amine
237N- [1- (4-chlorophenyl) cyclobutyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2385- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (diphenylmethyl) pyrimidin-2-amine
2395- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- { (1RS) -1- [3- (trifluoromethyl) phenyl ] ethyl } pyrimidin-2-amine
2405- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- { (1RS) -1- [2- (trifluoromethyl) phenyl ] ethyl } pyrimidin-2-amine
2415- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-fluorophenyl) cyclopropyl ] -N- (prop-2-yn-1-yl) pyrimidin-2-amine
242N- [1- (4-tert-butylphenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2435- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (3, 4-dimethoxyphenyl) cyclopropyl ] pyrimidin-2-amine
244N- [ (R) -cyclopentyl (4-fluorophenyl) methyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2455- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1, 2-diphenylethyl ] pyrimidin-2-amine
246N- {1- [3- (difluoromethoxy) phenyl ] cyclopropyl } -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
247N- {1- [4- (difluoromethoxy) phenyl ] cyclopropyl } -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
248N- {1- [2- (difluoromethoxy) phenyl ] cyclopropyl } -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2495- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- {1- [3- (trifluoromethyl) phenyl ] cyclopropyl } pyrimidin-2-amine
2505- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- {1- [4- (trifluoromethyl) phenyl ] cyclopropyl } pyrimidin-2-amine
251N- [1- (2, 5-dichlorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
252N- [1- (3, 4-dichlorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
253N- [1- (2, 3-dichlorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
254N- [1- (3, 5-dichlorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
255N- [1- (2, 4-dichlorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2565- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- {2- [3- (trifluoromethyl) phenyl ] propan-2-yl } pyrimidin-2-amine
2575- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- { (1RS) -1- [3- (trifluoromethoxy) phenyl ] ethyl } pyrimidin-2-amine
258N- [1- (3-chlorophenyl) cyclohexyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
259N- [1- (4-chloro-3-nitrophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
260N- [ (1RS) -1- (2-bromophenyl) propyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
261N- (2, 2-Difluoroethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-fluorophenyl) cyclopropyl ] pyrimidin-2-amine
2625- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- {1- [3- (trifluoromethoxy) phenyl ] cyclopropyl } pyrimidin-2-amine
2635- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- {1- [ 2-fluoro-4- (trifluoromethyl) phenyl ] cyclopropyl } pyrimidin-2-amine
264N- [1- (4, 5-dichloro-2-fluorophenyl) cyclopropyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
2655- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (3-phenoxyphenyl) cyclopropyl ] pyrimidin-2-amine
2665- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- {1- [4- (trifluoromethyl) phenyl ] cyclopentyl } pyrimidin-2-amine
267N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -2, 2, 2-trifluoro-N- [1- (2-fluorophenyl) cyclopropyl ] acetamide
268N- [1- (2-bromophenyl) cyclohexyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
In some embodiments, the present invention relates to the use of compounds of formula (I) and their salts, N-oxides, solvates and optical or geometric isomers for controlling phytopathogenic fungi:
wherein
U is C containing 2 to 7 halogen atoms1-C3-a halogenated alkyl group,the halogen atoms may be the same or different and are selected from fluorine and chlorine;
Q1Is O or S;
W1and W2Independently N, CH or CF;
a is selected from a direct bond, O, NR4、-(C＝O)-、-(C＝S)-、-O-(C＝O)、-O-(C＝S)-、-N(R4)-(C＝O)-、-N(R4)-(C＝S)-、-(C＝O)-O-、-(C＝S)-O-、-(C＝O)-N(R5)-、-(C＝S)-N(R5)-、-O-N(R5)-、-N(R4)-O-、-N(R4)-N(R5)-、-O-(C＝O)-N(R5)-、-O-(C＝S)-N(R5)-、-N(R4)-(C＝O)-O-、-N(R4)-(C＝S)-O-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5)-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5)-、-O-(C＝O)-O-、-O-(C＝S)-O-；
m is 0 or 1;
p is 0, 1 or 2;
x is fluorine;
R1and R2Independently selected from hydrogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkenyl, C2-C8-haloalkenyl, C2-C8-alkynyl, C2-C8-haloalkynyl, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C2-C8-alkenyl and C2-C8Alkynyl may be interrupted by one or more R1aAnd R2aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl groups may be independently substituted by one or more R1bAnd R2bSubstituent group substitution; or
R1And R2May form C together with the carbon atom to which they are attached3-C7-cycloalkyl or a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, wherein C is3-C7Cycloalkyl and a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring may be interrupted by one or more R1bSubstituent group substitution;
R3is hydrogen, halogen, C 1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl may be substituted by one or more R3aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl may be substituted by one or more R3bSubstituent group substitution;
R4and R5Independently selected from hydrogen atom, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C2-C8-alkenyl, C2-C8-haloalkenyl, C3-C8-alkynyl, C3-C8-haloalkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, formyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, C1-C8Alkoxycarbonyl, C1-C8-haloalkoxycarbonyl, C1-C8-alkylsulfonyl, C1-C8Haloalkylsulfonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C2-C8-alkenyl, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8Alkoxycarbonyl and C1-C8The alkylsulfonyl radicals may be independently substituted by one or more R4aAnd R5aIs substituted by a substituent, and wherein said C is 3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8The alkyl and phenylsulfonyl groups may each be substituted by one or more R4bAnd R5bSubstituent group substitution;
R1a、R2a、R3a、R4aand R5aIndependently selected from nitro, hydroxy, cyano, carboxy, amino, sulfanyl, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms 1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
R1b、R2b、R3b、R4band R5bIndependently selected from halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group, amino group, sulfanyl group, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8Haloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C 1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
with the proviso that the compound of formula (I) is not:
-2-isopropyl-5, 6-dimethyl-3- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } pyridin-4-ol [2133324-02-2 ];
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6 ].
In the above formula (I), U is preferably C containing 2 to 3 halogen atoms1-haloalkyl groups, the halogen atoms being identical or different and chosen from fluorine and chlorine, more preferably U is CHF2Or CF3。
In the above formula (I), Q1Preferably O.
In the above formula (I), W1Preferably N or CH.
In the above formula (I), W2Preferably N or CH.
In some embodiments of formula (I) above, W 1And W2Is N, or W1Is N and W2Is CH.
In the above formula (I), A is preferably O, NR4、-(C＝O)-、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5) More preferably, a is NH, - (C ═ O) -O-, - (C ═ O) -NH-, or- (C ═ O) -NMe-.
In some embodiments, in formula (I) above, A is NR4NH is preferred.
In the above formula (I), p is preferably 0 or 1, more preferably p is 0.
In the above formula (I), R1And R2Preferably independently selected from hydrogen, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8Alkyl and heteroaryl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8Alkyl and heteroaryl-C1-C8-alkyl may be substituted as described herein, or R1And R2Together with the carbon atom to which they are attached form C3-C7-a cycloalkyl group.
In the above formula (I), R1More preferably selected from hydrogen, C1-C8-an alkyl group.
In the above formula (I), R2More preferably selected from hydrogen, C1-C8-an alkyl group.
In the above formula (I), R is more preferred1And R2May form C together with the carbon atom to which they are attached3-C6-cycloalkyl or a 3-to 6-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, even more preferably R1And R2May form a cyclopropyl or cyclobutyl ring together with the carbon atom to which they are attached.
In the above formula (I), R3Preferably selected from hydrogen, C1-C8-alkyl, aryl and heterocyclyl, wherein said C is1-C8-alkyl, aryl and heterocyclyl may be substituted as described herein.
In the above formula (I), R3More preferably selected from hydrogen, optionally substituted by C1-C8-alkoxy-substituted C1-C8Alkyl (e.g. 2-methoxyethyl), unsubstituted or substituted aryl and unsubstituted or substituted heterocyclyl.
In the above formula (I), R4And R5Preferably selected from hydrogen atom, C1-C8Alkyl radical, C1-C8-alkoxy, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl radical, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, C1-C8-alkylsulfonyl, C1-C8-haloalkylsulfonyl, aryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl radical, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, C1-C8-alkylsulfonyl, C1-C8-haloalkylsulfonyl, aryl-C1-C8-alkyl and phenylsulfonyl may be substituted as described herein.
In the above formula (I), R4More preferably hydrogen or C1-C8Alkyl, in particular hydrogen.
In the above formula (I), R5More preferably hydrogen or C 1-C8Alkyl, in particular hydrogen.
The preferences mentioned above with respect to the substituents of the compounds of the invention can be combined in various ways. Thus, the combination of these preferred features provides a subclass of compounds of the present invention. Examples of such subclasses of preferred compounds of the invention are:
preferred features of U with Q1、W1、W2、A、p、R1、R2、R3、R4And R5One or more preferred features of (a);
-Q1preferred features of (2) and U, W1、W2、A、p、R1、R2、R3、R4And R5One or more preferred features of (a);
-W1preferred features of (2) and U, Q1、W2、A、p、R1、R2、R3、R4And R5One or more preferred features of (a);
-W2preferred features of (2) and U, Q1、W1、A、p、R1、R2、R3、R4And R5One or more preferred features of (a);
preferred features of A with U, Q1、W1、W2、p、R1、R2、R3、R4And R5One or more preferred features of (a);
preferred features of p with U, Q1、W1、W2、A、R1、R2、R3、R4And R5One or more preferred features of (a);
-R1preferred features of (2) and U, Q1、W1、W2、A、p、R2、R3、R4And R5One or more preferred features of (a);
-R2preferred features of (2) and U, Q1、W1、W2、A、p、R1、R3、R4And R5One or more preferred features of (a);
-R3preferred features of (2) and U, Q1、W1、W2、A、p、R1、R2、R4And R5One or more preferred features of (a);
-R4preferred features of (2) and U, Q1、W1、W2、A、p、R1、R2、R3And R5One or more preferred features of (a);
-R5preferred features of (2) and U, Q1、W1、W2、A、p、R1、R2、R3And R4One or more preferred features of (a);
in these combinations of preferred features of substituents of the compounds of the invention, said preferred features may also be selected from U, Q 1、W1、W2、A、p、R1、R2、R3、R4And R5Each of the more preferred features to form the most preferred subclass of compounds of the invention.
The present invention relates to compounds of formula (I):
wherein
U is C containing 2 to 7 halogen atoms1-C3-haloalkyl groups, the halogen atoms being identical or different and selected from fluorine and chlorine;
Q1is O or S;
a is selected from a direct bond, O, NR4、S、S＝O、S(＝O)2、-(C＝O)-、-(C＝S)-、-O-(C＝O)-、-O-(C＝S)-、-N(R4)-(C＝O)-、-N(R4)-(C＝S)-、-(C＝O)-O-、-(C＝S)-O-、-(C＝O)-N(R5)-、-(C＝S)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-(C＝S)-N(R4)-N(R5)-、-O-N(R5)-、-N(R4)-O-、-N(R4)-N(R5)-、-O-(C＝O)-N(R5)-、-O-(C＝S)-N(R5)-、-N(R4)-(C＝O)-O-、-N(R4)-(C＝S)-O-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5)-、-O-(C＝O)-O-、-O-(C＝S)-O-；
W1And W2Independently N, CH or CF;
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0, 1 or 2;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkenyl, C2-C8-haloalkenyl, C2-C8-alkynyl, C2-C8-haloalkynyl, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C2-C8-alkenyl and C2-C8Alkynyl may be interrupted by one or more R1aAnd R2aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl groups may be independently substituted by one or more R1bAnd R2bSubstituent group substitution; or
R1And R2May form C together with the carbon atom to which they are attached 3-C7-cycloalkyl or a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, wherein C is3-C7-cycloalkyl and 3-memberedThe up to 10 membered saturated or partially unsaturated heterocyclyl ring may be substituted with one or more R1bSubstituent group substitution; or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring, wherein said C3-C7The cycloalkyl ring may be interrupted by one or more R1bSubstituent group substitution;
R3is hydrogen, halogen, borono, (trifluoro) boron alkyl potassium, di- (C)1-C8-alkoxy) boryl, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein the 1, 3, 2-dioxaborolan-2-yl and 1, 3, 2-dioxaborolan-2-yl groups may be substituted by one to four C1-C3-alkyl substituents, and wherein said C is 1-C8Alkyl may be substituted by one or more R3aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl may be substituted by one or more R3bSubstituent group substitution;
R4and R5Independently selected from hydrogen atom, hydroxyl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C2-C8-alkenyl, C2-C8-haloalkenyl, C3-C8-alkynyl, C3-C8-haloalkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, formyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, arylcarbonyl, C1-C8Alkoxycarbonyl, C1-C8-haloalkoxycarbonyl, C1-C8-alkylsulfonyl, C1-C8Haloalkylsulfonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C2-C8-alkenyl, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8Alkoxycarbonyl and C1-C8The alkylsulfonyl radicals may be independently substituted by one or more R4aAnd R5aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, arylcarbonyl, aryl, heteroaryl, aryl-C 1-C8-alkyl, heteroaryl-C1-C8The alkyl and phenylsulfonyl groups may each be substituted by one or more R4bAnd R5bSubstituent group substitution;
R1a、R2a、R3a、R4aand R5aIndependently selected from halogen, nitro, hydroxy, cyano, carboxy, amino, sulfanyl, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8-alkoxy radicalRadical, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C 1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
R1b、R2b、R3b、R4band R5bIndependently selected from halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group, amino group, sulfanyl group, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8Haloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8-alkanesOxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms 1-C8Halogenoalkylsulfanyl, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
with the proviso that when m is 1 or 2 and W1And W2When N is present, A is not NR4；
Provided that when W1And W2When it is CH, U is not CCl3Or CHCl2；
With the proviso that the compound of formula (I) is not:
-2, 5-bis [5- (trichloromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [222190-08-1],
-2- (bromomethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [2071232-31-8],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-methylpyridine [2071232-29-4],
-2-chloro-5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [2011795-38-1],
-2-chloro-5- [5- (dichloromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [160152-11-4],
-2- {5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -1H-benzimidazole-7-carboxamide [1103394-47-3],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- { (4-fluorophenyl) [1- (methylsulfonyl) azetidin-3-yl ] methyl } pyrimidin-2-amine [2243579-66-8],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (methylsulfonyl) pyrimidine [2095318-34-4],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (methylsulfanyl) pyrimidine [2095318-33-3 ].
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6],
-N- [2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) -2- (tetrahydro-2H-pyran-4-yl) ethyl ] methanesulfonamide [2243579-65-7],
-1- [4- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) -4-isopropylpiperidin-1-yl ] ethanone [2243579-38-4],
-N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -2, 2-difluoro-N- [1- (4-fluorophenyl) -2- {3- [ (methylsulfonyl) amino ] phenyl } ethyl ] acetamide [2243577-58-2],
-N- [ 2-cyclopropyl-2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) ethyl ] methanesulfonamide [2243577-21-9],
-N- [ 2-cyclopropyl-2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) ethyl ] methanesulfonamide [2243577-20-8],
-N- [ 2-cyclopropyl-2- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) ethyl ] methanesulfonamide [2243577-19-5],
-N- [ cyclopropyl (4-fluorophenyl) methyl ] -N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -2, 2-difluoroacetamide [2243576-38-5],
-N- [ cyclopropyl (4-fluorophenyl) methyl ] -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine [2243576-35-2],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-isopropylcyclopropyl) pyrimidin-2-amine [2243576-06-7],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- [ (1-phenylcyclopropyl) oxy ] pyrimidine [2243575-46-2], and
-N- [ (6-methylpyridin-2-yl) methyl ] -5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine [2243575-26-8],
-2- (difluoromethyl) -5- (4-iodophenyl) -1, 3, 4-oxadiazole [2244172-62-9],
-2-isopropyl-5, 6-dimethyl-3- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } pyridin-4-ol [2133324-02-2],
-2- [4- (bromomethyl) -3-fluorophenyl ] -5- (trifluoromethyl) -1, 3, 4-oxadiazole [2098919-34-5],
-N- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } butan-1-amine [2080363-69-3],
-2- [4- (chloromethyl) phenyl ] -5- (difluoromethyl) -1, 3, 4-oxadiazole [2071231-55-3],
-2- [4- (bromomethyl) -3-fluorophenyl ] -5- (difluoromethyl) -1, 3, 4-oxadiazole [2071227-85-3],
-2- (difluoromethyl) -5- (3-fluoro-4-methylphenyl) -1, 3, 4-oxadiazole [2071227-84-2],
-1- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } methanamine hydrochloride (1: 1) [2071226-91-8],
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } methanesulfonamide [2071223-51-1],
-methyl 4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [1352872-14-0],
-2- (trifluoromethyl) -5- [4- (trifluoromethyl) phenyl ] -1, 3, 4-oxadiazole [1352872-13-9],
-2- (4-tert-butylphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1352872-12-8],
-2- (4-methylphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1352872-11-7],
methyl- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenoxy } acetate [1227372-86-2],
-ethyl 2- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenoxy } propanoate [1227372-85-1],
-2- (4-bromophenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [918476-23-0],
-4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] aniline [904643-35-2],
-2- ([ biphenyl ] -4-yl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [887267-97-2],
-2- [4- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl ] -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1056456-25-7],
-2- (4-chlorophenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [627073-36-3],
-2- (4-methoxyphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [371950-64-0],
-2- (dichloromethyl) -5- (4-methoxyphenyl) -1, 3, 4-oxadiazole [214195-06-9],
-2- (4-tert-butylphenyl) -5- (dichloromethyl) -1, 3, 4-oxadiazole [160152-26-1],
-2- (dichloromethyl) -5- (4-ethoxyphenyl) -1, 3, 4-oxadiazole [160152-21-6],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-fluoropyridine [2137870-57-4], and
-4- [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl ] aniline [2275439-93-3],
-2- ({4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoyl } oxy) -1H-isoindole-1, 3(2H) -dione [2248417-20-9],
-tert-butyl 4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [2241139-66-0],
-methyl 4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [2230804-32-5],
-4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] aniline [2160335-34-0],
-4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzaldehyde [2138236-86-7],
-2- (difluoromethyl) -5- (4-fluorophenyl) -1, 3, 4-oxadiazole [2137866-38-5],
-2- (4-bromophenyl) -5- (difluoromethyl) -1, 3, 4-oxadiazole [2137697-81-3],
-4- [5- (pentafluoroethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1920768-68-8],
-4- [5- (1, 1, 2, 2-tetrafluoroethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1917442-65-9],
-4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1282022-66-5], and
-4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1197226-72-4 ].
In the above formula (I), U is preferably C containing 2 to 3 halogen atoms1-haloalkyl groups, the halogen atoms being identical or different and chosen from fluorine and chlorine. More preferably, U is selected from CHF2、CClF2And CF3Still more preferably, U is CHF2Or CF3Even more preferably, U is CHF2。
In some embodiments, in formula (I) above, Q1Preferably O.
In some embodiments of formula (I) above, W1And W2Is N, or W1Is N and W2Is CH, more preferably, W1And W2Is N.
In the above formula (I), A is preferably a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-。
In some embodiments, a is a direct bond, O, NR 4、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5) More preferably O, NH, - (C ═ O) -O-, - (C ═ O) -NH-, or- (C ═ O) -NMe-, even more preferably O or NH.
In some embodiments, in formula (I) above, A is NR4NH is preferred.
In some embodiments, in formula (I) above, a is O.
In some embodiments, in formula (I) above, m is preferably 0 or 1, more preferably m is 1.
In the above formula (I), p is preferably 0 or 1, more preferably p is 0.
In the above formula (I), each R1And each R2Preferably independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7-cycloalkyl and aryl, wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring.
In the above formula (I), R is more preferred1Selected from the group consisting of hydrogen, fluoro, chloro, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl, and
R2Selected from the group consisting of hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl and difluoromethyl,
or
R1And R2Can be connected with itThe carbon atoms to which they are attached together form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring, or
When m is 2, two consecutive R1May form, together with the carbon atom to which they are attached, a cyclopropyl, cyclobutyl or cyclopentyl ring.
In the above formula (I), even more preferred
m is 1, m is a linear chain,
R1selected from the group consisting of hydrogen, methyl, ethyl, trifluoromethyl, ethynyl and cyclopropyl, and
R2is a hydrogen atom, and is,
or
R1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl or oxetanyl ring, more preferably a cyclopropyl or cyclobutyl ring, and most preferably a cyclopropyl ring.
In some embodiments, in formula (I) above, at least [ CR ] is present1R2]Group, wherein R1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring,
wherein if m is 2, the other [ CR1R2]R of the radical1And R2Independently selected from hydrogen, fluoro, chloro, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl, or together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring.
In some embodiments, in formula (I) above, m is 1, and R is1And R2Together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring, more preferably a cyclopropyl, cyclobutyl or oxetanyl ring.
In some preferred embodiments, m is 1, and R is1And R2Together with the carbon atom to which they are attachedThe atoms together form a cyclopropyl or cyclobutyl ring, preferably a cyclopropyl ring.
In some other preferred embodiments, m is 1, and R is1And R2Together with the carbon atom to which they are attached form an oxetanyl ring.
In still other preferred embodiments of the present invention,
m is 1, m is a linear chain,
R1selected from the group consisting of hydrogen, methyl, ethyl, trifluoromethyl and cyclopropyl, and
R2is hydrogen.
In the above formula (I), R3Preferably selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy, wherein the 1, 3, 2-dioxaborolan-2-yl radical may be substituted by one to four C1-C3-alkyl substituent substituted, wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C 1-C8-haloalkoxy substituents, and wherein said C is3-C7-cycloalkyl, C3-C8The cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group.
In the above formula (I), R3More preferably selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methyl, ethyl, trifluoromethyl, and mixtures thereof,A methoxymethyl group; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and naphthyl; a heterocyclyl group selected from the group consisting of tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazacyclohexanyl, oxathiahexidinyl, thiomorpholinyl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, and isoquinolinyl; biphenyl, phenoxyphenyl and phenoxy;
And wherein said C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
In some preferred embodiments, R3Selected from aryl and heteroaryl. In these embodiments, it is preferred that aryl is selected from phenyl and naphthyl; the heteroaryl is selected from furyl (furyl), thiopheneA group selected from the group consisting of phenyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, and isoquinolinyl; and aryl and heteroaryl groups may be substituted with one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl.
In some embodiments, R in formula (I) above3Selected from phenyl and pyridine, wherein said phenyl and pyridine may be substituted with one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl. In these embodiments, R3More preferably phenyl, which is unsubstituted or substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl, preferably unsubstituted or substituted with one or two substituents independently selected from fluoro, chloro, bromo, methyl and methoxy.
In the above formula (I), R4And R5Preferably independently selected from hydrogen, hydroxy, C 1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted with one or two fluorine atoms.
In the above formula (I), R4And R5More preferably independently selected from hydrogen, hydroxy, C1-C4Alkyl radical, C1-C4-haloalkyl group, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C4-alkynyl, C1-C4-alkylcarbonyl group, C1-C4-haloalkylcarbonyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted by one or two fluorine atoms.
In the above formula (I), R4And R5Most preferably independently selected from hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-difluoroethyl, methoxy, ethoxy, prop-2-ynyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted with one or two fluorine atoms.
In some particularly preferred embodiments, R4And R5Is hydrogen.
Preferred are compounds of formula (I) and their salts, N-oxides, solvates and optical isomers or geometric isomers:
wherein
U is selected from CHF2、CClF2And CF3；
Q1Is O or S;
W1and W2Independently is N or CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR 1R2]The groups may be the same or different;
p is 0 or 1;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7Cycloalkyl and aryl, preferably hydrogen, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl and C3-C7-cycloalkyl, wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring;
R3selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy,
wherein the 1, 3, 2-dioxaborolan-2-yl may be substituted by one to four C1-C3-an alkyl substituent, and (C) a substituted alkyl group,
wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C1-C8-a haloalkoxy substituent, and
wherein said C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, benzene The oxyphenyl and aryloxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group;
R4and R5Independently selected from hydrogen, hydroxy, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted by one or two fluorine atoms;
with the proviso that when m is 1 or 2 and W1And W2When N is present, A is not NR4。
Particular preference is given to compounds of the formula (I) and their salts, N-oxides, solvates and optical or geometric isomers, in which
U is selected from CHF2、CClF2And CF3Especially CHF2Or CF3；
Q1Is O or S, preferably O;
W1and W2Independently is N or CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0;
R1selected from the group consisting of hydrogen, fluoro, chloro, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl,
Or when m is 2, two consecutive R1May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl or cyclopentyl ring, and
R2selected from hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl and difluoromethyl, or
R1And R2May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring;
R3selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and naphthyl; a heterocyclyl group selected from the group consisting of tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazacyclohexanyl, oxathiahexidinyl, thiomorpholinyl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl Oxazinyl, indolyl, isoindolyl, quinolinyl, and isoquinolinyl; biphenyl, phenoxyphenyl and phenoxy;
and wherein said C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl;
preferably, R3Selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and 2-naphthyl; a heterocyclyl group selected from piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, morpholin-4-yl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of 2-furyl (furyl) (2-furyl), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, IH-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, and quinolin-2-yl; biphenyl, phenoxyphenyl and phenoxy;
And wherein said C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3bSubstituted by substituentSaid R is3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl;
R4and R5Independently selected from hydrogen, hydroxy, C1-C4Alkyl radical, C1-C4-haloalkyl group, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C4-alkynyl, C1-C4-alkylcarbonyl group, C1-C4-haloalkylcarbonyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted by one or two fluorine atoms, preferably R4And R5Independently selected from hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-difluoroethyl, methoxy, ethoxy, prop-2-ynyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted with one or two fluorine atoms;
with the proviso that when m is 1 or 2 and W1And W2When N is present, A is not NR4。
In some embodiments, U is CHF 2。
In some embodiments, W1And W2Is N, or W1Is N and W2Is CH.
In some embodiments, a is a direct bond, O, S, NR4、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5) -, more preferably O, S or NR4Even more preferably O or NR4Most preferably NH.
In some embodiments of the present invention, the substrate is,
R1selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, vinyl, ethynyl, phenyl and cyclopropyl,
R2is a hydrogen atom, and is,
or
R1And R2Together with itThe carbon atoms to which they are attached together form a cyclopropyl, cyclobutyl or oxetanyl ring, more preferably a cyclopropyl or cyclobutyl ring, and most preferably a cyclopropyl group.
In some embodiments, R3Is selected from C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl and heteroaryl, preferably C3-C7-cycloalkyl, aryl, heterocyclyl and heteroaryl; more preferably aryl or heteroaryl, and most preferably aryl;
wherein C is3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;
wherein C is3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl;
wherein aryl is selected from phenyl and naphthyl;
wherein the heterocyclyl group is selected from the group consisting of tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazacyclohexanyl, oxathioheterocycloalkyl, thiomorpholinyl and 1, 3-dihydro-2H-isoindol-2-yl, preferably from the group consisting of piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, dithiopyranyl and 1, 3-2H-isoindol-2-yl, preferably from the group consisting of piperidin-1-yl, piperazine-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, and thiapyran-yl, Morpholin-4-yl and 1, 3-dihydro-2H-isoindol-2-yl;
Wherein heteroaryl is selected from the group consisting of furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl and isoquinolinyl, preferably selected from the group consisting of 2-furyl (2-furyl), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl and quinolin-2-yl;
and wherein said C3-C7-cycloalkyl, C3-C8-the cycloalkenyl, aryl, heterocyclyl and heteroaryl groups may be substituted with one to three substituents independently selected from: fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl. In some such embodiments, R 3Selected from phenyl and pyridyl, wherein said phenyl and pyridyl may be substituted with one to three substituents independently selected from the group consisting of: fluorine, chlorine, bromine, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl. In these embodiments, R3More preferably phenyl, which is unsubstituted or substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl, especially unsubstituted phenyl or phenyl substituted with one or two substituents independently selected from fluoro, chloro, bromo, methyl and methoxy.
In some embodiments, R4And R5Is hydrogen.
Most preferred are compounds of formula (I) selected from:
I.0014- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid
0022- (difluoromethyl) -5- [4- (methylsulfanyl) phenyl ] -1, 3, 4-oxadiazole
0034- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid methyl ester
0044- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid
0052- (difluoromethyl) -5- [4- (1H-1, 2, 3-triazol-1-yl) phenyl ] -1, 3, 4-oxadiazole
0064- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid methyl ester
0072- ([ biphenyl ] -4-yl) -5- (difluoromethyl) -1, 3, 4-oxadiazole
I.0084- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzoic acid
0092- (4-bromophenyl) -5- (difluoromethyl) -1, 3, 4-oxadiazole
0102- (difluoromethyl) -5- [4- (1H-imidazol-1-ylmethyl) phenyl ] -1, 3, 4-oxadiazole
0114- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzoic acid methyl ester
012N- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } -2, 2-difluoroacetamide
013N- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } pyrimidin-2-amine
0142- ([ biphenyl ] -4-yl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole
0155- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } -3-ethyl-1, 2, 4-oxadiazol
0164- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methoxyethyl) benzamide
017N- {4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } -2-fluoroaniline
0183-Ethyl-5- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } -1, 2, 4-oxadiazol
I.0192, 2' - (1, 4-phenylene) bis [5- (difluoromethyl) -1, 3, 4-oxadiazole ]
020N- (2-methoxyethyl) -4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzamide 2- (difluoromethyl) -5- [4- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl ] -1, 3, 4-oxa-N-e
I.021 diazoles
0224- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methyl-N-phenylbenzamide
023N- (2-methoxyethyl) -4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzamide
0242- {4- [ (4-chlorophenoxy) methyl ] phenyl } -5- (difluoromethyl) -1, 3, 4-oxadiazole
0254- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (2-fluorophenyl) cyclopropyl ] aniline
026N-methyl-N-phenyl-4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzamide
0274- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2, 4-difluorophenyl) benzamide
028N- (2, 4-difluorophenyl) -4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzamide
029N- (2, 4-difluorophenyl) -4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzamide
0305- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-amine
I.0312-chloro-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine
0325- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine-2-carboxylic acid
0335- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methylpyridine-2-carboxamide
034N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } acetamide
0355- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-furanyl) pyridine
0365- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (1H-pyrazol-1-yl) pyridine
0375- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (trifluoromethyl) pyridine
I.038 {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } carbamic acid methyl ester
0395- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (prop-2-yn-1-yl) pyridine-2-carboxamide
0405- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (piperidin-1-yl) pyridine
0414- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } morpholine
0425- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N ', N' -dimethylpyridine-2-carbohydrazide
0435- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-phenoxypyridine
0445- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-methylcyclopropyl) pyridine-2-carboxamide
045N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -1-methylcyclopropanecarboxamide
046N- (cyclopropylmethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine-2-carboxamide
0475- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methoxyethyl) pyridine-2-carboxamide
0485- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (4-methylphenyl) pyridine-2-carboxamide
0495- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methyl-N-phenylpyridine-2-carboxamide
050N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -2-phenylacetamide
0511- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -3-phenylurea
0525- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1RS) -1- (4-fluorophenyl) ethyl ] pyridin-2-amine
0535- {5- [ chloro (difluoro) methyl ] -1, 3, 4-oxadiazol-2-yl } -N- (2-fluorophenyl) pyridin-2-amine
0545- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [1- (4-fluorophenyl) cyclopropyl ] pyridin-2-amine
055N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -2, 4-difluorobenzamide
0565- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- [ (1-phenylcyclopropyl) methyl ] pyridine-2-carboxamide
0575- {5- [ chloro (difluoro) methyl ] -1, 3, 4-oxadiazol-2-yl } -N- [1- (2-fluorophenyl) cyclopropyl ] pyridin-2-amine
0584- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } piperazine-1-carboxylic acid tert-butyl ester
0595- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
0605- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methylpyrimidin-2-amine
0612-chloro-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0625- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N, N-dimethylpyrimidin-2-amine
0645- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2, 2-dimethylhydrazino) pyrimidine
0652- (Cyclopent-1-en-1-yl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0665- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-methylcyclopropyl) pyrimidin-2-amine
0685- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methoxyethyl) pyrimidin-2-amine
0695- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-phenylpyrimidine
0705- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (pyridin-3-yl) pyrimidine
0715- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-thienyl) pyrimidine
0725- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (3-thienyl) pyrimidine
0744- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } morpholine
I.0752-benzyl-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0765- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-phenylpyrimidin-2-amine
0775- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (4-fluorophenyl) pyrimidine
0785- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (1-ethyl-1H-pyrazol-5-yl) pyrimidine
0795- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-fluoropyridin-4-yl) pyrimidine
0805- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (6-fluoropyridin-3-yl) pyrimidine
0815- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (3, 5-dimethyl-1, 2-oxazol-4-yl) pyrimidine
0832- (cyclohexylmethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0854- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } benzonitrile
0865- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methylphenyl) pyrimidin-2-amine
0875- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N-methyl-N-phenylpyrimidin-2-amine
0895- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (4-methoxyphenyl) pyrimidine
0902- (benzyloxy) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
0915- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (4-fluorobenzyl) pyrimidine
0925- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (phenylsulfanyl) pyrimidine
0935- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-fluorophenyl) pyrimidin-2-amine
0945- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (3-fluorophenyl) pyrimidin-2-amine
0955- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (4-fluorophenyl) pyrimidin-2-amine
0965- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-ethyl-1H-pyrazol-5-yl) pyrimidin-2-amine
0985- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (4-fluorophenoxy) pyrimidine
0992- (2-chlorophenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
1002- (3-chlorophenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
1012- (4-chlorophenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
1022- (2-Chloropyridin-4-yl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
1032- (5-Chloropyridin-3-yl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
I.1041- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) cyclopropanecarboxylic acid methyl ester
1062- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } isoindoline
1075- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-methoxybenzyl) pyrimidine
1085- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (2-methyl-2-phenylhydrazino) pyrimidine
1095- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (2-methoxyphenyl) pyrimidin-2-amine
I.1135- [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl ] -N- (2-fluorophenyl) pyrimidin-2-amine
I.114N- (2-chlorophenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1152- (2, 4-difluorobenzyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidine
I.116N- (2-fluorophenyl) -5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1171- ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) cyclopropanecarboxylic acid ethyl ester
119N- (2-Cyclopropylphenyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-amine
1205- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- [ (1-phenylcyclopropyl) oxy ] pyrimidine
1235- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [ (1RS) -1-phenylethyl ] sulfanyl } pyrimidine
1275- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [ (1RS) -1- (4-fluorophenyl) ethyl ] oxy } pyrimidine
130N- (2-fluorophenyl) -5- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] pyrimidin-2-amine
I.1425- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- [ (3-phenyloxetan-3-yl) oxy ] pyrimidine 5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [3- (pyridin-2-yl) oxetan-3-yl ] oxy } pyrimidine
I.143 pyridine
1495- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [1- (4-fluorophenyl) cyclopropyl ] oxy } pyrimidine
1675- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- { [1- (2, 6-difluorophenyl) cyclopropyl ] oxy } pyrimidine
185N- (2, 4-difluorobenzoyl) -N- {5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } -2, 4-difluorobenzamide
1875- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -N- (1-isopropylcyclopropyl) pyrimidin-2-amine
222 ({5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyrimidin-2-yl } amino) (pyridin-2-yl) acetic acid methyl ester
The present invention relates to compounds of formula (I-A) (i.e. wherein W1Compounds of formula (I) that are N) and their salts, N-oxides, solvates and optical isomers or geometric isomers:
wherein
U is C containing 2 to 7 halogen atoms1-C3-haloalkyl groups, the halogen atoms being identical or different and selected from fluorine and chlorine;
Q1is O or S;
W2is CH or CF;
a is selected from a direct bond, O, NR4、S、S＝O、S(＝O)2、-(C＝O)-、-(C＝S)-、-O-(C＝O)-、-O-(C＝S)-、-N(R4)-(C＝O)-、-N(R4)-(C＝S)-、-(C＝O)-O-、-(C＝S)-O-、-(C＝O)-N(R5)-、-(C＝S)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-(C＝S)-N(R4)-N(R5)-、-O-N(R5)-、-N(R4)-O-、-N(R4)-N(R5)-、-O-(C＝O)-N(R5)-、-O-(C＝S)-N(R5)-、-N(R4)-(C＝O)-O-、-N(R4)-(C＝S)-O-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5)-、-O-(C＝O)-O-、-O-(C＝S)-O-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0, 1, 2 or 3;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkenyl, C2-C8-haloalkenyl, C2-C8-alkynyl, C2-C8-haloalkynyl, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C2-C8-alkenyl and C2-C8Alkynyl may be interrupted by one or more R1aAnd R2aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-an alkyl group,heterocyclyl-C 1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl groups may be independently substituted by one or more R1bAnd R2bSubstituent group substitution; or
R1And R2May form C together with the carbon atom to which they are attached3-C7-cycloalkyl or a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, wherein C is3-C7Cycloalkyl and a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring may be interrupted by one or more R1bSubstituent group substitution; or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring, wherein said C3-C7The cycloalkyl ring may be interrupted by one or more R1bSubstituent group substitution;
R3is hydrogen, halogen, borono, (trifluoro) boron alkyl potassium, di- (C)1-C8-alkoxy) boryl, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C 3-C7-cycloalkyl-C1-C8-alkyl, wherein the 1, 3, 2-dioxaborolan-2-yl and 1, 3, 2-dioxaborolan-2-yl groups may be substituted by one to four C1-C3-alkyl substituents, and wherein said C is1-C8Alkyl may be substituted by one or more R3aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl radical、C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl may be substituted by one or more R3bSubstituent group substitution;
R4and R5Independently selected from hydrogen atom, hydroxyl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C2-C8-alkenyl, C2-C8-haloalkenyl, C3-C8-alkynyl, C3-C8-haloalkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, formyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, arylcarbonyl, C1-C8Alkoxycarbonyl, C1-C8-haloalkoxycarbonyl, C1-C8-alkylsulfonyl, C1-C8Haloalkylsulfonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C2-C8-alkenyl, C3-C8-alkynyl, C 1-C8-alkylcarbonyl group, C1-C8Alkoxycarbonyl and C1-C8The alkylsulfonyl radicals may be independently substituted by one or more R4aAnd R5aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, arylcarbonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonylMay be respectively substituted by one or more R4bAnd R5bSubstituent group substitution;
R1a、R2a、R3a、R4aand R5aIndependently selected from halogen, nitro, hydroxy, cyano, carboxy, amino, sulfanyl, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms 1-C8-haloalkylcarbonylamino, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
R1b、R2b、R3b、R4band R5bIndependently selected from halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group, amino group, sulfanyl group, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8Haloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C 1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
with the proviso that the compound of formula (I-A) is not:
-2, 5-bis [5- (trichloromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [222190-08-1],
-2- (bromomethyl) -5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [2071232-31-8],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-methylpyridine [2071232-29-4],
-2-chloro-5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [2011795-38-1], -2-chloro-5- [5- (dichloromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridine [160152-11-4], and
-2- {5- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] pyridin-2-yl } -1H-benzimidazole-7-carboxamide [1103394-47-3 ];
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2-fluoropyridine [2137870-57-4 ].
In the above formula (I-A), U is preferably C containing 2 to 3 halogen atoms1-haloalkyl groups, the halogen atoms being identical or different and chosen from fluorine and chlorine, more preferably U is CHF2Or CF3Even more preferably, U is CHF2。
In the above formula (I-A), Q1Preferably O.
In the above formula (I-A), W2Preferably CH.
In the above formula (I-A), A is preferably O, NR4、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5) More preferably a is O, NH, - (C ═ O) -O-, - (C ═ O) -NH-, or- (C ═ O) -NMe-, even more preferably O or NH.
In the above formula (I-A), p is preferably 0 or 1, more preferably p is 0.
In the above formula (I-A), m is preferably 0 or 1, more preferably m is 1.
In the above formula (I-A), R1Preferably selected from hydrogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl.
In the above formula (I-A), R2Preference is given toIs hydrogen or C1-C8-an alkyl group.
In the above formula (I-A), R is preferred1And R2May form C together with the carbon atom to which they are attached3-C6-cycloalkyl or a 3-to 6-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, more preferably R1And R 2May form, together with the carbon atom to which they are attached, a cyclopropyl, cyclobutyl or oxetanyl ring.
In the above formula (I-A), R3Preferably selected from hydrogen, optionally C1-C8-alkoxy-substituted C1-C8Alkyl (e.g. 2-methoxyethyl), unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl and unsubstituted or substituted heteroaryl.
In the above formula (I-A), R4Preferably hydrogen or C1-C8-an alkyl group.
In the above formula (I-A), R5Preferably hydrogen or C1-C8-an alkyl group.
Preference is given to compounds of the formula (I-A) and their salts, N-oxides, solvates and optical or geometric isomers, in which
U is selected from CHF2、CClF2And CF3；
Q1Is O or S;
W2is CH; a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0 or 1;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7Cycloalkyl and aryl, preferably selected from hydrogen, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl and C3-C7-a cycloalkyl group and an aryl group,
wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R 2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring;
R3selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy,
wherein the 1, 3, 2-dioxaborolan-2-yl may be substituted by one to four C1-C3-an alkyl substituent, and (C) a substituted alkyl group,
wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C1-C8-a haloalkoxy substituent, and
wherein said C3-C7-cycloalkyl, C3-C8The cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group;
R4and R5Independently selected from hydrogen, hydroxy, C1-C8Alkyl radical, C1-C8-haloalkyl group, C 1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted with one or two fluorine atoms.
Particular preference is given to compounds of the formula (I-A) and their salts, N-oxides, solvates and optical or geometric isomers, in which
U is selected from CHF2、CClF2And CF3Especially CHF2Or CF3；
Q1Is O;
W2is CH;
a is a direct bond, O, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0 or 1;
p is 0;
R1and R2Selected from the group consisting of hydrogen, methyl, ethynyl,
or
R1And R2May form a cyclopropyl ring together with the carbon atom to which they are attached;
R3selected from hydrogen, fluoro, bromo, chloro, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; cyclopropyl, phenyl; a heterocyclic group selected from the group consisting of piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, morpholin-4-yl, and 1, 3-dihydro-2H-iso-heterocyclylIndol-2-yl; and heteroaryl selected from 2-furyl (furyl) (2-furyl)), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, IH-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, and quinolin-2-yl; and wherein said cyclopropyl, phenyl, heterocyclyl and heteroaryl may be substituted with one to three R 3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl;
R4and R5Independently selected from hydrogen and methyl.
The present invention relates to compounds of formula (I-B) (i.e. wherein W1And W2Formula (I)) which is N and their salts, N-oxides, hydrates and optical or geometric isomers:
wherein
U is C containing 2 to 7 halogen atoms1-C3-haloalkyl groups, the halogen atoms being identical or different and selected from fluorine and chlorine;
Q1is O or S;
a is selected from a direct bond, O, NR4、S、S＝O、S(＝O)2、-(C＝O)-、-(C＝S)-、-O-(C＝O)-、-O-(C＝S)-、-N(R4)-(C＝O)-、-N(R4)-(C＝S)-、-(C＝O)-O-、-(C＝S)-O-、-(C＝O)-N(R5)-、-(C＝S)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-(C＝S)-N(R4)-N(R5)-、-O-N(R5)-、-N(R4)-O-、-N(R4)-N(R5)-、-O-(C＝O)-N(R5)-、-O-(C＝S)-N(R5)-、-N(R4)-(C＝O)-O-、-N(R4)-(C＝S)-O-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5)-、-O-(C＝O)-O-、-O-(C＝S)-O-；
With the proviso that when m is 1 or 2, A is not NR4；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0, 1 or 2;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkenyl, C2-C8-haloalkenyl, C2-C8-alkynyl, C2-C8-haloalkynyl, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C 1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C2-C8-alkenyl and C2-C8Alkynyl may be interrupted by one or more R1aAnd R2aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl groups may be independently substituted by one or more R1bAnd R2bSubstituent group substitution; or
R1And R2May form C together with the carbon atom to which they are attached3-C7-cycloalkyl or a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, wherein C is3-C7Cycloalkyl and a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring may be interrupted by one or more R1bSubstituent group substitution; or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring, wherein said C3-C7The cycloalkyl ring may be interrupted by one or more R1bSubstituent group substitution;
R3is hydrogen, halogen, borono, (trifluoro) boron alkyl potassium, di- (C)1-C8-alkoxy) boryl, 1, 3, 2-dioxaborolan-2-yl, C 1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein the 1, 3, 2-dioxaborolan-2-yl and 1, 3, 2-dioxaborolan-2-yl groups may be substituted by one to four C1-C3-alkyl substituents, and wherein said C is1-C8Alkyl may be substituted by one or more R3aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl andC3-C7-cycloalkyl-C1-C8Alkyl may be substituted by one or more R3bSubstituent group substitution;
R4and R5Independently selected from hydrogen atom, hydroxyl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C2-C8-alkenyl, C2-C8-haloalkenyl, C3-C8-alkynyl, C3-C8-haloalkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, formyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, arylcarbonyl, C 1-C8Alkoxycarbonyl, C1-C8-haloalkoxycarbonyl, C1-C8-alkylsulfonyl, C1-C8Haloalkylsulfonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C2-C8-alkenyl, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8Alkoxycarbonyl and C1-C8The alkylsulfonyl radicals may be independently substituted by one or more R4aAnd R5aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, arylcarbonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8The alkyl and phenylsulfonyl groups may each be substituted by one or more R4bAnd R5bSubstituent group substitution;
R1a、R2a、R3a、R4aand R5aIndependently selected from halogen, nitro, hydroxyl, cyano, carboxyl, amino, sulfanyl, and pentafluoro-λ6Sulfanyl, formyl, carbamoyl, carbamate, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C 1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
R1b、R2b、R3b、R4band R5bIndependently selected from halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group, amino group, sulfanyl group, pentafluoro-lambda6Sulfanyl, formyl, carbamoyl, carbamate, C1-C8Alkyl radical, C3-C7Cycloalkyl having 1 to 5 halogen atomsC of seed1-C8Haloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C 1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
with the proviso that the compound of formula (I-B) is not:
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- [ (1-phenylcyclopropyl) oxy ] pyrimidine [2243575-46-2],
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (methylsulfonyl) pyrimidine [2095318-34-4], and
-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] -2- (methylsulfanyl) pyrimidine [2095318-33-3 ].
In the above formula (I-B), U is preferably C containing 2 to 3 halogen atoms1-haloalkyl groups, the halogen atoms being identical or different and chosen from fluorine and chlorine, more preferably U is CHF2Or CF3Even more preferably, U is CHF2。
In the above formula (I-B), Q1Preferably O.
In the above formula (I-B), A is preferably O, S, NR4、-(C＝O)-、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5) More preferably a is O, S, NH, - (C ═ O) -O-, - (C ═ O) -NH-, or- (C ═ O) -NMe-, even more preferably O or NH.
In the above formula (I-A), p is preferably 0 or 1, more preferably p is 0.
In the above formula (I-B), m is preferably 0 or 1, more preferably m is 1.
In the above formula (I-B), R1Preferably selected from hydrogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl.
In the above formula (I-B), R2Preferably hydrogen or C1-C8-an alkyl group.
In the above formula (I-B), R is preferred1And R2May form C together with the carbon atom to which they are attached3-C6-cycloalkyl or a 3-to 6-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, more preferably R1And R2May form, together with the carbon atom to which they are attached, a cyclopropyl, cyclobutyl or oxetanyl ring.
In the above formula (I-B), R3Preferably selected from hydrogen, optionally C1-C8-alkoxy-substituted C1-C8Alkyl (e.g. 2-methoxyethyl), unsubstituted or substituted aryl, unsubstitutedSubstituted or substituted heterocyclyl and unsubstituted or substituted heteroaryl.
In the above formula (I-B), R4Preferably hydrogen or C1-C8-an alkyl group.
In the above formula (I-B), R5Preferably selected from hydrogen or C1-C8-an alkyl group.
Preference is given to compounds of the formula (I-B) and their salts, N-oxides, solvates and optical or geometric isomers, in which
U is selected from CHF2、CClF2And CF3；
Q1Is O or S;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
With the proviso that when m is 1 or 2, A is not NR4；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0 or 1;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7-cycloalkyl and aryl, wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached 3-C7-a cycloalkyl ring;
R3selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy,
wherein the 1, 3, 2-dioxaborolan-2-yl may be substituted by one to four C1-C3-an alkyl substituent, and (C) a substituted alkyl group,
wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C1-C8-a haloalkoxy substituent, and
wherein said C3-C7-cycloalkyl, C3-C8The cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group;
R4and R5Independently selected from hydrogen, hydroxy, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted with one or two fluorine atoms.
Particular preference is given to compounds of the formula (I-B) and their salts, N-oxides, solvates and optical or geometric isomers, in which
U is selected from CHF2、CClF2And CF3Especially CHF2Or CF3；
Q1Is O or S, preferably O;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
With the proviso that when m is 1 or 2, A is not NR4；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0;
R1selected from the group consisting of hydrogen, fluoro, chloro, cyano, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, trifluoromethyl, difluoromethyl, vinyl, ethynyl, phenyl, cyclopentyl, cyclobutyl and cyclopropyl,
or when m is 2, two consecutive R1May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl or cyclopentyl ring, and
R2selected from the group consisting of hydrogen, fluorine, chlorine, methyl, ethyl, trifluoromethyl and difluoromethyl,
or
R1And R2May form together with the carbon atom to which they are attached a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl ring;
R3selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c 3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and naphthyl; heterocyclic group ofHeterocyclyl is selected from tetrahydrofuranyl, 1, 3-dioxolanyl, tetrahydrothienyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, isoxazolidinyl, oxazolidinyl, oxadiazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, piperidinyl, hexahydropyridazinyl, hexahydropyrimidinyl, piperazinyl, triazacyclohexyl, hexahydrotriazinyl, tetrahydropyranyl, dioxanyl, tetrahydrothiopyranyl, dithianyl, morpholinyl, 1, 2-oxazacyclohexanyl, oxathianyl, thiomorpholinyl and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of furyl (furyl), thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, quinolinyl, and isoquinolinyl; biphenyl, phenoxyphenyl and phenoxy;
and wherein said C 3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl;
preferably, R3Selected from the group consisting of hydrogen, fluoro, bromo, chloro, 1, 3, 2-dioxaborolan-2-yl, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl; c3-C7-cycloalkyl, said C3-C7-cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; c3-C8-cycloalkenyl radical, said C3-C8-cycloalkenyl is selected from cyclopentenyl and cyclohexenyl; aryl selected from phenyl and 2-naphthyl; heterocyclic radical selected fromFrom piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, morpholin-4-yl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of 2-furyl (furyl) (2-furyl), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, and quinolin-2-yl; biphenyl, phenoxyphenyl and phenoxy;
And wherein said C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and phenoxy groups may be substituted by one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxycarbonyl, ethoxycarbonyl and tert-butoxycarbonyl;
R4and R5Independently selected from hydrogen, hydroxy, C1-C4Alkyl radical, C1-C4-haloalkyl group, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C4-alkynyl, C1-C4-alkylcarbonyl group, C1-C4-haloalkylcarbonyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted by one or two fluorine atoms, preferably R4And R5Independently selected from hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-difluoroethyl, methoxy, ethoxy, prop-2-ynyl and phenylcarbonyl, wherein the phenylcarbonyl may be substituted with one or two fluorine atoms.
The present invention relates to compounds of formula (I-C) and their salts, N-oxides, solvates and optical isomers or geometric isomers:
Wherein
U is C containing 2 to 7 halogen atoms1-C3-haloalkyl groups, the halogen atoms being identical or different and selected from fluorine and chlorine; provided that U is not CCl3Or CHCl2；
Q1Is O or S;
W1and W2Independently selected from CF and CH;
a is selected from a direct bond, O, NR4、S、S＝O、S(＝O)2、-(C＝O)-、-(C＝S)-、-O-(C＝O)-、-O-(C＝S)-、-N(R4)-(C＝O)-、-N(R4)-(C＝S)-、-(C＝O)-O-、-(C＝S)-O-、-(C＝O)-N(R5)-、-(C＝S)-N(R5)-、-(C＝O)-N(R4)-N(R5)-、-(C＝S)-N(R4)-N(R5)-、-O-N(R5)-、-N(R4)-O-、-N(R4)-N(R5)-、-O-(C＝O)-N(R5)-、-O-(C＝S)-N(R5)-、-N(R4)-(C＝O)-O-、-N(R4)-(C＝S)-O-、-N(R4)-(C＝O)-N(R5)-、-N(R4)-(C＝S)-N(R5)-、-O-(C＝O)-O-、-O-(C＝S)-O-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0, 1, 2, 3 or 4;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkenyl, C2-C8-haloalkenyl, C2-C8-alkynyl, C2-C8-haloalkynyl, C3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein said C1-C8Alkyl radical, C2-C8-alkenyl and C2-C8Alkynyl may be interrupted by one or more R1aAnd R2aIs substituted by a substituent, and wherein said C is3-C7Cycloalkyl, aryl, heterocyclyl, heteroaryl, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl groups may be independently substituted by one or more R1bAnd R2bSubstituent group substitution; or
R1And R2May form C together with the carbon atom to which they are attached3-C7-cycloalkyl or a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, wherein C is 3-C7Cycloalkyl and a 3-to 10-membered saturated or partially unsaturated heterocyclyl ring may be interrupted by one or more R1bSubstituent group substitution; or
When m is 2, two consecutive R1May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl ring, wherein said C3-C7The cycloalkyl ring may be interrupted by one or more R1bSubstituent group substitution;
R3is hydrogen, halogen, borono, (trifluoro) boron alkyl potassium, di- (C)1-C8-alkoxy) boryl, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8-alkyl, wherein the 1, 3, 2-dioxaborolan-2-yl and 1, 3, 2-dioxaborolan-2-yl groups may be substituted by one to four C1-C3-alkyl substituents, and wherein said C is1-C8Alkyl may be substituted by one or more R3aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl, aryloxy, heterocyclyloxy, heteroaryloxy, aryl-C 1-C8-alkyl, heterocyclyl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and C3-C7-cycloalkyl-C1-C8Alkyl may be substituted by one or more R3bSubstituent group substitution;
R4and R5Independently selected from hydrogen atom, hydroxyl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C2-C8-alkenyl, C2-C8-haloalkenyl, C3-C8-alkynyl, C3-C8-haloalkynyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, formyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl, arylcarbonyl, C1-C8Alkoxycarbonyl, C1-C8-haloalkoxycarbonyl, C1-C8-alkylsulfonyl, C1-C8Haloalkylsulfonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8Alkyl radical, C1-C8-alkoxy, C2-C8-alkenyl, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8Alkoxycarbonyl and C1-C8The alkylsulfonyl radicals may be independently substituted by one or more R4aAnd R5aIs substituted by a substituent, and wherein said C is3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8Alkyl, arylcarbonyl, aryl, heteroaryl, aryl-C1-C8-alkyl, heteroaryl-C1-C8The alkyl and phenylsulfonyl groups may each be substituted by one or more R4bAnd R5bSubstituent group substitution;
R1a、R2a、R3a、R4aand R5aIndependently selected from halogen, nitro, hydroxy, cyano, carboxy, amino, sulfanyl, pentafluoro-lambda 6Sulfanyl, formyl, carbamoyl, carbamate, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
R1b、R2b、R3b、R4band R5bIndependently selected from halogen atom, nitro group, hydroxyl group, cyano group, carboxyl group, amino group, sulfanyl group, pentafluoro-lambda 6Sulfanyl, formyl, carbamoyl, carbamate, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8Haloalkyl, C having 1 to 5 halogen atoms3-C7-halocycloalkyl, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino radical, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylcarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8Alkoxycarbonyl, C having 1 to 5 halogen atoms1-C8-haloalkoxycarbonyl, C1-C8-alkylcarbonyloxy, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonyloxy, C1-C8-alkylcarbonylamino, C having 1 to 5 halogen atoms1-C8-haloalkylcarbonylamino, C1-C8Alkylsulfanyl, C having 1 to 5 halogen atoms1-C8Halogenoalkylsulfanyl, C1-C8-alkylsulfinyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfinyl, C1-C8-alkylsulfonyl, C having 1 to 5 halogen atoms1-C8-haloalkylsulfonyl, C1-C8-alkylsulfonylamino, C having 1 to 5 halogen atoms 1-C8Haloalkylsulfonylamino, sulfamoyl, C1-C8-alkylsulfamoyl and di-C1-C8-an alkylsulfamoyl group;
with the proviso that the compound of formula (I-C) is not:
-N- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } cyclopropanecarboxamide [2376135-82-7],
- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenyl } carbamic acid tert-butyl ester [2376135-81-6],
-2- (difluoromethyl) -5- (4-iodophenyl) -1, 3, 4-oxadiazole [2244172-62-9],
-2-isopropyl-5, 6-dimethyl-3- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzyl } pyridin-4-ol [2133324-02-2],
-2- [4- (bromomethyl) -3-fluorophenyl ] -5- (trifluoromethyl) -1, 3, 4-oxadiazole [2098919-34-5],
-2- [4- (chloromethyl) phenyl ] -5- (difluoromethyl) -1, 3, 4-oxadiazole [2071231-55-3],
-2- [4- (bromomethyl) -3-fluorophenyl ] -5- (difluoromethyl) -1, 3, 4-oxadiazole [2071227-85-3],
-2- (difluoromethyl) -5- (3-fluoro-4-methylphenyl) -1, 3, 4-oxadiazole [2071227-84-2],
-methyl 4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [1352872-14-0],
-2- (trifluoromethyl) -5- [4- (trifluoromethyl) phenyl ] -1, 3, 4-oxadiazole [1352872-13-9],
-2- (4-tert-butylphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1352872-12-8],
-2- (4-methylphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1352872-11-7],
methyl- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenoxy } acetate [1227372-86-2],
-ethyl 2- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] phenoxy } propanoate [1227372-85-1],
-2- [4- (4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl ] -5- (trifluoromethyl) -1, 3, 4-oxadiazole [1056456-25-7],
-2- (4-bromophenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [918476-23-0],
-4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] aniline [904643-35-2],
-2- ([ biphenyl ] -4-yl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [887267-97-2],
-2- (4-chlorophenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [627073-36-3],
-2- (4-methoxyphenyl) -5- (trifluoromethyl) -1, 3, 4-oxadiazole [371950-64-0],
-4- [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl ] aniline [2275439-93-3],
-2- ({4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoyl } oxy) -1H-isoindole-1, 3(2H) -dione [2248417-20-9],
-tert-butyl 4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [2241139-66-0],
-methyl 4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoate [2230804-32-5],
-4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] aniline [2160335-34-0],
-4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzaldehyde [2138236-86-7],
-2- (difluoromethyl) -5- (4-fluorophenyl) -1, 3, 4-oxadiazole [2137866-38-5],
-2- (4-bromophenyl) -5- (difluoromethyl) -1, 3, 4-oxadiazole [2137697-81-3],
-4- [5- (pentafluoroethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1920768-68-8],
-4- [5- (1, 1, 2, 2-tetrafluoroethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1917442-65-9],
-4- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1282022-66-5], and
-4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl ] benzoic acid [1197226-72-4 ].
In the above formula (I-C), U is preferably C containing 2 to 3 halogen atoms1-haloalkyl, the halogen atoms being identical or different and being chosen from fluorine and chlorine, with the proviso that U is not CCl3Or CHCl2More preferably, U is CHF2Or CF3Even more preferably, U is CHF2。
In the above formula (I-C), Q1Preferably O.
In the above formula (I-C), A is preferably O, NR4、-(C＝O)-、-N(R4) - (C ═ O) -, - (C ═ O) -O-, or- (C ═ O) -N (R)5) More preferably a is O, NH, - (C ═ O) -O-, - (C ═ O) -NH-, or- (C ═ O) -NMe-, even more preferably O or NH.
In the above formula (I-C), p is preferably 0 or 1, more preferably p is 0.
In the above formula (I-C), m is preferably 0 or 1, more preferably m is 1.
In the above formula (I-C), R1Preferably selected from hydrogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-Cs-alkynyl.
In the above formula (I-C), R2Preferably hydrogen or C1-C8-an alkyl group.
In the above formula (I-C), R is preferred1And R2May form C together with the carbon atom to which they are attached3-C6-cycloalkyl or a 3-to 6-membered saturated or partially unsaturated heterocyclyl ring comprising 1 to 3 heteroatoms, which may be the same or different, and are selected from O, S and NH, more preferably R1And R2May form, together with the carbon atom to which they are attached, a cyclopropyl, cyclobutyl or oxetanyl ring.
In the above formula (I-C), R3Preferably selected from hydrogen, optionally C1-C8-alkoxy-substituted C1-C8Alkyl (e.g. 2-methoxyethyl), unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl and unsubstituted or substituted heteroaryl.
In the above formula (I-C), R4Preferably hydrogen or C1-C8-an alkyl group.
In the above formula (I-C), R5Preferably hydrogen or C1-C8-an alkyl group.
Preference is given to compounds of the formula (I-C) and their salts, N-oxides, solvates and optical or geometric isomers, in which
U is selected from CHF2、CClF2And CF3；
Q1Is O or S;
W1and W2Is CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5)-、-(C＝O)-N(R4)-N(R5)、-N(R4)-N(R5)-、-N(R4) - (C ═ O) -O-or-N (R)4)-(C＝O)-N(R5)-；
m is 0, 1 or 2; wherein if m is 2, then two [ CR1R2]The groups may be the same or different;
p is 0 or 1;
x is fluorine;
each R1And each R2Independently selected from hydrogen, halogen, cyano, C1-C8Alkyl radical, C1-C8-haloalkyl group, C2-C8-alkynyl, C3-C7-cycloalkyl and aryl, wherein said C1-C8The alkyl group may be substituted by one or more groups selected from hydroxy and C1-C8Substituted by alkoxy, or
R1And R2May form C together with the carbon atom to which they are attached3-C7-a cycloalkyl or oxetanyl ring, or
When m is 2, two consecutive R1May be formed together with the carbon atom to which they are attachedC3-C7-a cycloalkyl ring;
R3selected from hydrogen, halogen, 1, 3, 2-dioxaborolan-2-yl, C1-C8Alkyl radical, C1-C8-haloalkyl group, C3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy,
wherein the 1, 3, 2-dioxaborolan-2-yl may be substituted by one to four C1-C3-an alkyl substituent, and (C) a substituted alkyl group,
wherein said C1-C8The alkyl group may be substituted by a C1-C8-alkoxy or C1-C8-a haloalkoxy substituent, and
wherein said C 3-C7-cycloalkyl, C3-C8Cycloalkenyl, aryl, heterocyclyl, heteroaryl, biphenyl, phenoxyphenyl and aryloxy may be substituted with one to three R3b substituents, said R3bThe substituents are independently selected from halogen, nitro, cyano, C1-C8Alkyl radical, C3-C7Cycloalkyl, C having 1 to 5 halogen atoms1-C8-haloalkyl group, C1-C8Alkoxy, C having 1 to 5 halogen atoms1-C8-haloalkoxy and C1-C8-an alkoxycarbonyl group;
R4and R5Independently selected from hydrogen, hydroxy, C1-C8Alkyl radical, C1-C8-haloalkyl group, C1-C8-alkoxy, C1-C8-haloalkoxy, C3-C8-alkynyl, C1-C8-alkylcarbonyl group, C1-C8-haloalkylcarbonyl and arylcarbonyl, wherein the arylcarbonyl may be substituted with one or two fluorine atoms.
Particular preference is given to compounds of the formula (I-C) and their salts, N-oxides, solvates and optical or geometric isomers, in which
U isCHF2Or CF3；
Q1Is O or S, preferably O;
W1and W2Is CH;
a is a direct bond, O, S, NR4、-N(R4)-(C＝O)、-(C＝O)-O-、-(C＝O)-N(R5) -or- (C ═ O) -N (R)4)-N(R5)；
m is 0 or 1;
p is 0;
R1and R2Selected from the group consisting of hydrogen and methyl,
or
R1And R2May form a cyclopropyl ring together with the carbon atom to which they are attached;
R3selected from the group consisting of hydrogen, fluoro, bromo, chloro, methyl, ethyl, trifluoromethyl, difluoromethyl, 2-methoxyethyl, 1-methoxyethyl, methoxymethyl, and 1, 3, 2-dioxaborolan-2-yl; a phenyl group; a heterocyclyl group selected from piperidin-1-yl, piperazin-1-yl, tetrahydro-2H-pyran-4-yl, tetrahydrothiopyran-4-yl, morpholin-4-yl, and 1, 3-dihydro-2H-isoindol-2-yl; heteroaryl selected from the group consisting of 2-furyl (furyl) (2-furyl), 2-thienyl, 3-thienyl, 1H-pyrazol-5-yl, 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 1H-1, 2, 3-triazol-1-yl, 1, 2-oxazol-4-yl, 1, 3, 4-oxadiazol-2-yl, 1, 2, 4-oxadiazol-5-yl, 1, 3-thiazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, and quinolin-2-yl; and a phenoxy group;
Wherein said 1, 3, 2-dioxaborolan-2-yl may be substituted with one to four methyl substituents,
and wherein said phenyl, heterocyclyl, heteroaryl and phenoxy groups may be substituted with one to three R3bSubstituted by a substituent, said R3bThe substituents are independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, nitro, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, trifluoromethoxy, difluoromethoxy, methoxyCarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl;
R4and R5Independently selected from hydrogen and methyl.
Compounds of formula (I), including (I-A), (I-B) and (I-C), are useful for controlling phytopathogenic fungi (for use as fungicides). The present invention therefore relates to the use of compounds of the formulae (I), (I-A), (I-B) and (I-C) for controlling phytopathogenic fungi.
The present invention also relates to any of the compounds of formula (I) disclosed in table 1.
Intermediates for the preparation of active ingredients
The invention also relates to intermediates useful in the preparation of compounds of formula (I).
Unless otherwise indicated, groups and subscripts U, Q1、W1、W2、A、p、m、R1、R2、R3、R4And R5Have the meanings given above for the compounds of formula (I).
Accordingly, the present invention relates to compounds of formula (IIa) and acceptable salts thereof:
wherein
U is CHF2Or CF3，
Provided that when m is 1 and W1And W2When both are N, then A is not NH;
with the proviso that the compound of formula (IIa) does not represent:
-2- [ (1-benzylcyclobutyl) amino ] -N' - (difluoroacetyl) pyrimidine-5-carbohydrazide [2095319-66-5],
-N' - (difluoroacetyl) -2- (methylsulfanyl) pyrimidine-5-carbohydrazide [2095318-32-2],
-N' - (difluoroacetyl) -3-fluoro-4-methylbenzoyl hydrazine [2071227-83-1],
-6-chloro-N' - (trifluoroacetyl) nicotinoyl [2011795-44-9],
-4-methoxy-N' - (trifluoroacetyl) benzoyl hydrazine [314283-32-4], and
-4-methyl-N' - (trifluoroacetyl) benzoyl hydrazine [304668-19-7 ].
The chemical databases and/or the supplier databases also mention the compounds of formula (IIa) below, but there is no reference or information to be able to prepare and isolate them:
-4- (1H-tetrazol-1-yl) -N' - (trifluoroacetyl) benzoylhydrazine [1209426-58-3],
-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) benzamide [651709-76-1],
-4-tert-butyl-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) benzamide [642935-44-2],
-4- (dimethylamino) -N' - (trifluoroacetyl) benzoyl hydrazine [494200-26-9],
-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) cyclohexanecarboxamide [443666-63-5],
-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) cyclopropanecarboxamide [443636-89-3],
-2, 2, 2-trifluoro-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) acetamide [357163-15-6],
-2-methyl-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) benzamide [356767-83-4],
-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) butanamide [356766-87-5],
-3-methyl-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) benzamide [356525-80-9],
-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) propanamide [349641-09-4],
-4-chloro-N' - (trifluoroacetyl) benzoyl hydrazine [349639-35-6],
-N- (4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } phenyl) acetamide [314767-09-4], and
-N' - (trifluoroacetyl) [ biphenyl ] -4-carbohydrazide [307339-48-6 ].
Preferred compounds of formula (IIa) according to the invention are:
-N' - (difluoroacetyl) -4- (methylsulfanyl) benzoyl hydrazine,
-N- (4- { [2- (difluoroacetyl) hydrazino ] carbonyl } phenyl) acetamide,
-methyl 4- { [2- (difluoroacetyl) hydrazino ] carbonyl } benzoate,
-4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } benzoic acid,
-N' - (difluoroacetyl) -4- (1H-1, 2, 3-triazol-1-yl) benzoylhydrazine,
-methyl 4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } benzoate,
-N' - (difluoroacetyl) [ biphenyl ] -4-carbohydrazide,
-4-bromo-N' - (difluoroacetyl) benzoyl hydrazine,
-N' - (difluoroacetyl) -4- (1H-imidazol-1-ylmethyl) benzoyl hydrazine,
-N' - (difluoroacetyl) -4- (pyrimidin-2-ylamino) benzoyl hydrazine,
-N' - (difluoroacetyl) -4- (3-ethyl-1, 2, 4-oxadiazol-5-yl) benzoylhydrazine,
-4- { [2- (difluoroacetyl) hydrazino ] carbonyl } -N- (2-methoxyethyl) benzamide,
-N' - (difluoroacetyl) -4- (2-fluoroanilino) benzoyl hydrazine,
-4- (3-ethyl-1, 2, 4-oxadiazol-5-yl) -N' - (trifluoroacetyl) benzoylhydrazine,
-N- (2-methoxyethyl) -4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } benzamide,
-4- { [2- (difluoroacetyl) hydrazino ] carbonyl } -N-methyl-N-phenylbenzamide,
-N '1, N' 4-bis (difluoroacetyl) terephthalamide (terephthalamohydrazide),
-4- [ (4-chlorophenoxy) methyl ] -N' - (difluoroacetyl) benzoyl hydrazine,
-N-methyl-N-phenyl-4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } benzamide,
-4- { [2- (difluoroacetyl) hydrazino ] carbonyl } -N- (2, 4-difluorophenyl) benzamide,
-N- (2, 4-difluorophenyl) -4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } benzamide,
-N' - (difluoroacetyl) -6- (2-furyl) nicotinoyl hydrazine,
-N' - (difluoroacetyl) -6- (trifluoromethyl) nicotinoyl hydrazine,
-N' - (difluoroacetyl) -6- (piperidin-1-yl) nicotinyl hydrazide,
-N' - (difluoroacetyl) -6-phenoxynicotinoyl hydrazine,
-tert-butyl 4- (5- { [2- (difluoroacetyl) hydrazino ] carbonyl } pyridin-2-yl) piperazine-1-carboxylate,
-N' - (difluoroacetyl) -2- (morpholin-4-yl) pyrimidine-5-carbohydrazide,
-N' - (difluoroacetyl) -2- (2-fluoroanilino) pyrimidine-5-carbohydrazide,
-2- (2-fluoroanilino) -N' - (trifluoroacetyl) pyrimidine-5-carbohydrazide,
-ethyl 1- [ (5- { [2- (difluoroacetyl) hydrazino ] carbonyl } pyrimidin-2-yl) amino ] cyclopropanecarboxylate, and
-N' - (difluoroacetyl) -2- { [ (1RS) -1-phenylethyl ] sulfanyl } pyrimidine-5-carbohydrazide.
Process for preparing compounds of formula (I) and intermediates
The present invention relates to a process for the preparation of compounds of formula (I) and intermediates thereof. Unless otherwise indicated, groups and subscripts U, Q1、W1、W2、A、p、m、R1、R2、R3、R4And R5Have the meanings given above for the compounds of formula (I). These definitions apply not only to the end products of formula (I) but also to all intermediates.
Wherein Q 1Compounds of formula (Ia) ═ O can be prepared according to method P1 by reacting the intermediate of formula (II) with a dehydrating agent such as methyl N- (triethylsulfonylammonium) carbamate (Burgess reagent) in a suitable solvent such as tetrahydrofuran, as previously described in WO 2017065473.
Wherein Q1Compounds of formula (Ib) ═ S can be prepared according to method P2 by reacting the intermediate of formula (II) with a sulfurizing agent such as Lawesson' S reagent (2, 4-bis (4-methoxyphenyl) -1, 3, 2, 4-dithiodiphosphetane (dithiadiphosphetane) -2, 4-dithione) in a suitable solvent such as toluene or tetrahydrofuran, as previously described in org.lett., 2006, 8, 1625-.
The intermediates of formula (II) are commercially available or can be prepared according to method P3 by reacting carbohydrazide of formula (III) with C1-C3-haloalkylacetic anhydride or C1-C3Haloalkylacetyl chloride (which is commercially available or can be prepared according to known procedures starting from readily available compounds) is prepared in a suitable solvent (for example tetrahydrofuran), optionally in the presence of a base (for example triethylamine), preferably by reaction at room temperature, as previously described in WO 2017065473.
Carbohydrazides of formula (III) are commercially available or can be prepared according to method P4 by reacting a compound of formula (IV) wherein LG1 is a leaving group, e.g. ethoxy, with hydrazine hydrate in a suitable solvent, e.g. ethanol, as previously described in WO 2017065473.
The compounds of formula (IV) are commercially available or can be prepared according to known procedures starting from readily available compounds.
Or, wherein A is O or NR4The compound of formula (IV') can be prepared according to process P5 by reacting a compound of formula (V), which isWherein LG1 is an alkoxy group, e.g., ethoxy, and wherein LG2 is a leaving group, e.g., chloro, is reacted with a compound of formula (VI), optionally in the presence of a base, e.g., N-diisopropylethylamine, or an acid, e.g., p-toluenesulfonic acid, in a solvent, e.g., dichloromethane or 1, 4-dioxane, by nucleophilic substitution (as described, e.g., in European Journal of Medicinal Chemistry, 135, 531-543; 2017 or Bioorganic&Medicinal Chemistry, 25(17), 4553-4559; 2017). When LG2 is SMe, it may be desirable to activate the leaving group, for example by oxidation with 3-chloroperbenzoic acid.
The compounds of formula (V) are commercially available or can be prepared according to known procedures starting from readily available compounds.
The compounds of formula (VI) are commercially available or can be prepared according to known procedures starting from readily available compounds.
Alternatively, carbohydrazides of formula (III) can be prepared according to method P6 by reacting a compound of formula (VII) with an acid (e.g., trifluoroacetic acid) in a suitable solvent (e.g., dichloromethane), preferably at room temperature, as described previously in Bioorganic & Medicinal Chemistry, 20(1), 487-497; 2012.
The compounds of formula (VII) are commercially available or may be prepared according to method P7 by reacting an acid of formula (VIII) with tert-butyl carbazate (tert-butyl carbazate) in the presence of a coupling agent (e.g. 1- [ bis (dimethylamino) methylene ] -1H-1, 2, 3-triazolo [4, 5-b ] pyridinium 3-oxi-Hexafluorophosphate (HATU) or 1, 3-propanediamine, N3- (ethylcarboimino) -N1, N1-dimethyl-hydrochloride (EDCI)) in a suitable solvent (e.g. dichloromethane), optionally in the presence of a base (e.g. N, N-diisopropylethylamine), as previously described in Tetrahedron, 58(27), 5513-; 2002.
The compounds of formula (VIII) are commercially available or can be prepared according to known procedures starting from readily available compounds.
Or, wherein A is O or NR4The compound of formula (Ic) of (a) can be prepared according to process P8 from a compound of formula (IX) wherein LG3 is a leaving group, optionally in the presence of a base (e.g. triethylamine) or an acid (e.g. P-toluenesulfonic acid) by nucleophilic substitution with a compound of formula (VI) in a solvent (e.g. dichloromethane or 1, 4-dioxane) (as described, for example, in European Journal of Medicinal Chemistry, 135, 531-543; 2017 or WO 2017065473). When LG2 is SMe, it may be desirable to activate the leaving group, for example by oxidation with 3-chloroperbenzoic acid.
The compounds of formula (IX) are commercially available or can be prepared analogously to methods P1 or P2 and P3 or P4 and P5 starting from readily available compounds.
According to the invention, the processes P1 to P8 can be carried out in the presence of a solvent where appropriate and in the presence of a base where appropriate.
Suitable solvents for carrying out the processes P1 to P8 according to the invention are conventional inert organic solvents. Preference is given to using optionally halogenated aliphatic, cycloaliphatic or aromatic hydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin (decalin); chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxyethane, 1, 2-diethoxyethane or anisole; nitriles, such as acetonitrile, propionitrile, n-or isobutyronitrile or benzonitrile; amides, such as N, N-dimethylformamide, N-dimethylacetamide, N-methylformanilide (N-methylformanilide), N-methylpyrrolidone or hexamethylphosphoric triamide (hexamethylphosphoric triamide); esters, such as methyl acetate or ethyl acetate; sulfoxides, such as dimethyl sulfoxide; or sulfones, such as sulfolane.
Suitable bases for carrying out the processes P1 to P8 according to the invention are the inorganic and organic bases conventionally used for the reactions. Preference is given to using alkaline earth metals, alkali metal hydrides, alkali metal hydroxides or alkali metal alkoxides, such as sodium hydroxide, sodium hydride, calcium hydroxide, potassium tert-butoxide; or other ammonium hydroxides; alkali metal carbonates such as sodium carbonate, potassium bicarbonate, sodium bicarbonate, cesium carbonate; alkali metal or alkaline earth metal acetates such as sodium acetate, potassium acetate, calcium acetate; and tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine, N-dimethylaniline, pyridine, N-methylpiperidine, N-dimethylaminopyridine, 1, 4-diazabicyclo [2.2.2] octane (DABCO), 1, 5-diazabicyclo [4.3.0] non-5-ene (DBN) or 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU).
According to the invention, the reaction temperature can be varied independently within a wide range when carrying out the processes P1 to P8. Typically, the process of the invention is carried out at a temperature of from-20 ℃ to 160 ℃. The way of controlling the temperature of the process is to use microwave technology.
The processes P1 to P8 of the invention are generally carried out independently at atmospheric pressure. However, it is also possible to carry out under elevated pressure or reduced pressure.
The work-up is carried out by conventional methods. Typically, the reaction mixture is treated with water and the organic phase is separated off and, after drying, concentrated under reduced pressure. The residue remaining may, if appropriate, be separated from any impurities which may still be present by conventional methods, for example chromatography or recrystallization.
The compounds of the invention may be prepared according to the methods described above. It will be understood, however, that based on the common general knowledge of the skilled person and the available publications, it is possible to adapt these methods according to the particular circumstances of each of the compounds of the invention which it is desired to synthesize.
Various aspects of the present teachings may be further understood in light of the following examples, which should not be construed as in any way limiting the scope of the present teachings.
Compositions and formulations
The invention also relates to a composition, in particular a composition for controlling unwanted phytopathogenic microorganisms. The composition may be applied to the microorganism and/or its habitat.
The compositions generally comprise at least one compound of formula (I) and at least one agriculturally suitable adjuvant, such as one or more carriers and/or one or more surfactants.
The carrier is a generally inert solid or liquid, natural or synthetic organic or inorganic substance. The carrier generally improves the application of the compound, for example, on the plant, plant part or seed. Examples of suitable solid supports include, but are not limited to, ammonium salts, natural rock flour (e.g., kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth), and synthetic rock flour (e.g., finely divided silica, alumina and silicates). Examples of useful solid carriers commonly used to prepare granules include, but are not limited to, crushed and fractionated natural rocks (e.g., calcite, marble, pumice, sepiolite and dolomite), synthetic granules of inorganic and organic flours, and granules of organic materials (e.g., paper, sawdust, coconut shells, corn cobs and tobacco stalks). Examples of suitable liquid carriers include, but are not limited to, water, organic solvents, and combinations thereof. Examples of suitable solvents include polar and non-polar organic chemical liquids, for example from the following classes: aromatic and non-aromatic hydrocarbons (e.g. cyclohexane, paraffin, alkylbenzenes, xylenes, tolylalkylnaphthalenes, chlorinated aromatic or aliphatic hydrocarbons such as chlorobenzene, vinyl chloride or dichloromethane), alcohols and polyols (which may also be optionally substituted, etherified and/or esterified, such as butanol or ethylene glycol), ketones (e.g. acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone), esters (including fats and oils) and (poly) ethers, unsubstituted and substituted amines, amides (e.g. dimethylformamide), lactams (e.g. N-alkylpyrrolidones) and lactones, sulfones and sulfoxides (e.g. dimethyl sulfoxide) o carriers may also be liquefied gaseous extenders, i.e. liquids which are gaseous at standard temperature and standard pressure, such as aerosol propellants, for example halogenated hydrocarbons, butanes, propane, nitrogen and carbon dioxide. The amount of carrier is typically from 1 to 99.99 wt%, preferably from 5 to 99.9 wt%, more preferably from 10 to 99.5 wt%, and most preferably from 20 to 99 wt% of the composition.
The surfactant may be an ionic (cationic or anionic) or a non-ionic surfactant, such as an ionic or non-ionic emulsifier, a foam former, a dispersant, a wetting agent, and any mixtures thereof. Examples of suitable surfactants include, but are not limited to, salts of polyacrylic acids, salts of lignosulfonic acids, salts of phenolsulfonic or naphthalenesulfonic acids, polycondensates of ethylene oxide and/or propylene oxide with fatty alcohols, fatty acids or fatty amines (polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, e.g. alkylaryl polyglycol ethers), substituted phenols (preferably alkylphenols or arylphenols), salts of sulfosuccinic esters, taurine derivatives (preferably alkyltaurates), phosphoric esters of polyethoxylated alcohols or phenols, fatty esters of polyhydric alcohols and derivatives of compounds containing sulfate, sulfonate, phosphate groups (e.g. alkylsulfonates, alkylsulfates, arylsulfonates), as well as protein hydrolysates, lignosulfite waste liquors and methylcellulose. When the compound of formula (I) and/or the carrier are insoluble in water and are administered with water, a surfactant is generally used. The amount of surfactant is then typically from 5 to 40% by weight of the composition.
Further examples of suitable auxiliaries include water repellents, drying agents, binders (adhesives), tackifiers, fixatives, for example carboxymethylcellulose, natural and synthetic polymers in powder, granule or latex form, for example gum arabic, polyvinyl alcohol and polyvinyl acetate, natural phospholipids, for example cephalins and lecithins, and synthetic phospholipids, polyvinylpyrrolidone and methylcellulose, thickeners, stabilizers, for example low-temperature stabilizers, preservatives, antioxidants, light stabilizers or other agents which improve the chemical and/or physical stability, dyes or pigments, for example inorganic pigments, for example iron oxide, titanium oxide and Prussian blue, organic dyes, for example alizarin, azo and metal phthalocyanine dyes, antifoams, for example silicone antifoams and magnesium stearate, preservatives, for example dichlorobenzene and hemiformal, Secondary thickeners (cellulose derivatives, acrylic acid derivatives, xanthan gum, modified clays and finely divided silica), binders, gibberellins and processing aids, mineral and vegetable oils, perfumes, waxes, nutrients (including micronutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc), protective colloids, thixotropic substances, penetrants, chelating agents and complexing agents.
The choice of adjuvant is related to the intended mode of administration and/or physical characteristics of the compound of formula (I). Furthermore, the adjuvants may be selected so as to impart specific properties (technical, physical and/or biological) to the composition or to the use form prepared therefrom. The choice of adjuvant may allow the composition to be tailored to specific needs.
The compositions may be in any conventional form, for example solutions (e.g. aqueous solutions), emulsions, wettable powders, water-and oil-based suspensions, powders, dusts, pastes, soluble powders, soluble granules, granules for broadcasting, suspoemulsion concentrates, natural or synthetic products impregnated with a compound of formula (I), fertilizers and microcapsules in polymers. The compounds of formula (I) may be present in suspended, emulsified or dissolved form.
The composition may be provided to the end user as a ready-to-use formulation, i.e. the composition may be applied directly to the plant or seed by a suitable device, such as a spraying or dusting device. Alternatively, the composition may be provided to the end user in the form of a concentrate which must be diluted, preferably with water, before use.
The compositions may be prepared in a conventional manner, for example by mixing a compound of formula (I) with one or more suitable auxiliaries, for example as disclosed above.
The composition typically contains from 0.01 to 99 wt%, from 0.05 to 98 wt%, preferably from 0.1 to 95 wt%, more preferably from 0.5 to 90 wt%, most preferably from 1 to 80 wt% of the compound of formula (I). The composition may comprise two or more compounds of formula (I). In this case, the range refers to the total amount of the compound of the present invention.
Mixtures/combinations
The compounds of formula (I) and compositions containing them may be mixed with other active ingredients such as fungicides, bactericides, acaricides, nematicides, insecticides, herbicides, fertilizers, growth regulators, safeners or semiochemicals. This may broaden the spectrum of activity or prevent the development of resistance. Examples of known fungicides, insecticides, acaricides, nematicides and bactericides are disclosed in the handbook of pesticides (Pesticide Manual), 17 th edition.
Examples of particularly preferred fungicides which can be mixed with the compounds of formula (I) and the compositions are:
1) ergosterol biosynthesis inhibitors, such as (1.001) cyproconazole (cyproconazole), (1.002) difenoconazole (difenoconazole), (1.003) epoxiconazole (epoxyconazole), (1.004) fenhexamid (fenhexamid), (1.005) fenpropidin (fenpropidin), (1.006) fenpropimorph (fenpropimorph), (1.007) fenpyrazamide (fenpyrazamine), (1.008) fluquinconazole (fluquinconazole), (1.009) flutriafol, (1.010) imazalil (imazalil), (1.011) imazalil sulfate (imazalil), (1.012) ipconazole, (1.013) metconazole (metconazole), (1.014) fenpropiconazole (1.022), (1.022) propiconazole (fenpyrazalil), (1.017) propiconazole (fenpyraclostrobin), (1.017) propiconazole (propiconazole), (1.010) propiconazole (propiconazole), (1.017) propiconazole (1.022) propiconazole (propiconazole), (1.023) propiconazole (propiconazole) (1.023) propiconazole) (1.024) Klinomyces (tridemorph), (1.025) triticonazole (triticonazole), (1.026) (1R, 2S, 5S) -5- (4-chlorobenzyl) -2- (chloromethyl) -2-methyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol, (1.027) (1S, 2R, 5R) -5- (4-chlorobenzyl) -2- (chloromethyl) -2-methyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol, (1.028) (2R) -2- (1-chlorocyclopropyl) -4- [ (1R) -2, 2-dichlorocyclopropyl ] -1- (1H-1, 2, 4-triazol-1-yl) butan-2-ol, (1.029) (2R) -2- (1-chlorocyclopropyl) -4- [ (1S) -2, 2-dichlorocyclopropyl ] -1- (1H-1, 2, 4-triazol-1-yl) butan-2-ol, (1.030) (2R) -2- [4- (4-chlorophenoxy) -2- (trifluoromethyl) phenyl ] -1- (1H-1, 2, 4-triazol-1-yl) propan-2-ol, (1.031) (2S) -2- (1-chlorocyclopropyl) -4- [ (1R) -2, 2-dichlorocyclopropyl ] -1- (1H-1, 2, 4-triazol-1-yl) butan-2-ol, (1.032) (2S) -2- (1-chlorocyclopropyl) -4- [ (1S) -2, 2-dichlorocyclopropyl ] -1- (1H-1, 2, 4-triazol-1-yl) butan-2-ol, (1.033) (2S) -2- [4- (4-chlorophenoxy) -2- (trifluoromethyl) phenyl ] -1- (1H-1, 2, 4-triazol-1-yl) propan-2-ol, (1.034) (R) - [3- (4-chloro-2-fluorophenyl) -5- (2, 4-difluorophenyl) -1, 2-oxazol-4-yl ] (pyridin-3-yl) methanol, (1.035) (S) - [3- (4-chloro-2-fluorophenyl) -5- (2, 4-difluorophenyl) -1, 2-oxazol-4-yl ] (pyridin-3-yl) methanol, (1.036) [3- (4-chloro-2-fluorophenyl) -5- (2, 4-difluorophenyl) -1, 2-oxazol-4-yl ] (pyridin-3-yl) methanol, (1.037)1- ({ (2R, 4S) -2- [ 2-chloro-4- (4-chlorophenoxy) phenyl ] -4-methyl-1, 3-dioxolan-2-yl } methyl) -1H-1, 2, 4-triazole, (1.038)1- ({ (2S, 4S) -2- [ 2-chloro-4- (4-chlorophenoxy) phenyl ] -4-methyl-1, 3-dioxolan-2-yl } methyl) -1H-1, 2, 4-triazole, (1.039)1- { [3- (2-chlorophenyl) -2- (2, 4-difluorophenyl) oxetan-2-yl ] methyl } -1H-1, 2, 4-triazol-5-yl thiocyanate, (1.040)1- { [ rel (2R, 3R) -3- (2-chlorophenyl) -2- (2, 4-difluorophenyl) oxetan-2-yl methyl } -1H-1, 2, 4-triazol-5-yl thiocyanate, (1.041)1- { [ rel (2R, 3S) -3- (2-chlorophenyl) -2- (2, 4-difluorophenyl) oxetan-2-yl ] methyl } -1H-1, 2, 4-triazol-5-yl thiocyanate, (1.042)2- [ (2R, 4R, 5R) -1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-thione, (1.043)2- [ (2R, 4R, 5S) -1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.044)2- [ (2R, 4S, 5R) -1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.045)2- [ (2R, 4S, 5S) -1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.046)2- [ (2S, 4R, 5R) -1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.047)2- [ (2S, 4R, 5S) -1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.048)2- [ (2S, 4S, 5R) -1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.049)2- [ (2S, 4S, 5S) -1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.050)2- [1- (2, 4-dichlorophenyl) -5-hydroxy-2, 6, 6-trimethylhept-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.051)2- [ 2-chloro-4- (2, 4-dichlorophenoxy) phenyl ] -1- (1H-1, 2, 4-triazol-1-yl) propan-2-ol, (1.052)2- [ 2-chloro-4- (4-chlorophenoxy) phenyl ] -1- (1H-1, 2, 4-triazol-1-yl) butan-2-ol, (1.053)2- [4- (4-chlorophenoxy) -2- (trifluoromethyl) phenyl ] -1- (1H-1, 2, 4-triazol-1-yl) butan-2-ol, (1.054)2- [4- (4-chlorophenoxy) -2- (trifluoromethyl) phenyl ] -1- (1H-1, 2, 4-triazol-1-yl) pentan-2-ol, (1.055) chlorofluoromethoxyfen-azole (Mefentrifluconazole), (1.056)2- { [3- (2-chlorophenyl) -2- (2, 4-difluorophenyl) oxetan-2-yl ] methyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-thione, (1.057)2- { [ rel (2R, 3R) -3- (2-chlorophenyl) -2- (2, 4-difluorophenyl) oxetan-2-yl ] methyl } -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.058)2- { [ rel (2R, 3S) -3- (2-chlorophenyl) -2- (2, 4-difluorophenyl) oxetan-2-yl ] methyl } -2, 4-dihydro-3H-1, 2, 4-triazole-3-thione, (1.059)5- (4-chlorobenzyl) -2- (chloromethyl) -2-methyl-1- (1H-1, 2, 4-triazole-1-ylmethyl) cyclopentanol, (1.060)5- (allylsulfanyl) -1- { [3- (2-chlorophenyl) -2-methyl-1- (1H-1, 4-triazole-1-ylmethyl) cyclopentanol - (2, 4-difluorophenyl) oxetan-2-yl ] methyl } -1H-1, 2, 4-triazole, (1.061)5- (allylsulfanyl) -1- { [ rel (2R, 3R) -3- (2-chlorophenyl) -2- (2, 4-difluorophenyl) oxetan-2-yl ] methyl } -1H-1, 2, 4-triazole, (1.062)5- (allylsulfanyl) -1- { [ rel (2R, 3S) -3- (2-chlorophenyl) -2- (2, 4-difluorophenyl) oxetan-2-yl ] methyl } -1H-1, 2, 4-triazole, (1.063) N '- (2, 5-dimethyl-4- { [3- (1, 1, 2, 2-tetrafluoroethoxy) phenyl ] sulfanyl } phenyl) -N-ethyl-N-methyliminocarboxamide, (1.064) N' - (2, 5-dimethyl-4- { [3- (2, 2, 2-trifluoroethoxy) phenyl ] sulfanyl } phenyl) -N-ethyl-N-methyliminocarboxamide, (1.065) N '- (2, 5-dimethyl-4- { [3- (2, 2, 3, 3-tetrafluoropropoxy) phenyl ] sulfanyl } phenyl) -N-ethyl-N-methyliminocarboxamide, (1.066) N' - (2, 5-dimethyl-4- { [3- (pentafluoroethoxy) phenyl ] sulfanyl } phenyl) -N-ethyl-N-methyliminocarboxamide, (1.067) N ' - (2, 5-dimethyl-4- {3- [ (1, 1, 2, 2-tetrafluoroethyl) sulfanyl ] phenoxy } phenyl) -N-ethyl-N-methyliminocarboxamide, (1.068) N ' - (2, 5-dimethyl-4- {3- [ (2, 2, 2-trifluoroethyl) sulfanyl ] phenoxy } phenyl) -N-ethyl-N-methyliminocarboxamide, (1.069) N ' - (2, 5-dimethyl-4- {3- [ (2, 2, 3, 3-tetrafluoropropyl) sulfanyl ] phenoxy } phenyl) -N-ethyl-N-methyliminocarboxamide, (1.070) N '- (2, 5-dimethyl-4- {3- [ (pentafluoroethyl) sulfanyl ] phenoxy } phenyl) -N-ethyl-N-methyliminocarboxamide, (1.071) N' - (2, 5-dimethyl-4-phenoxyphenyl) -N-ethyl-N-methyliminocarboxamide, (1.072) N '- (4- { [3- (difluoromethoxy) phenyl ] sulfanyl } -2, 5-dimethylphenyl) -N-ethyl-N-methyliminocarboxamide, (1.073) N' - (4- {3- [ (difluoromethyl) sulfanyl ] phenoxy } -2, 5-dimethylphenyl) -N-ethyl-N-methyliminocarboxamide, (1.074) N ' - [ 5-bromo-6- (2, 3-dihydro-1H-inden-2-yloxy) -2-methylpyridin-3-yl ] -N-ethyl-N-methyliminocarboxamide, (1.075) N ' - {4- [ (4, 5-dichloro-1, 3-thiazol-2-yl) oxy ] -2, 5-dimethylphenyl } -N-ethyl-N-methyliminocarboxamide, (1.076) N ' - { 5-bromo-6- [ (1R) -1- (3, 5-difluorophenyl) ethoxy ] -2-methylpyridin-3-yl } -N-methyliminocarboxamide -ethyl-N-methyliminocarboxamide, (1.077) N ' - { 5-bromo-6- [ (1S) -1- (3, 5-difluorophenyl) ethoxy ] -2-methylpyridin-3-yl } -N-ethyl-N-methyliminocarboxamide, (1.078) N ' - { 5-bromo-6- [ (cis-4-isopropylcyclohexyl) oxy ] -2-methylpyridin-3-yl } -N-ethyl-N-methyliminocarboxamide, (1.079) N ' - { 5-bromo-6- [ (trans-4-isopropylcyclohexyl) oxy ] -2-methylpyridin-3-yl } -N-ethyl-N-methyliminocarboxamide, and pharmaceutically acceptable salts thereof, (1.080) N' - { 5-bromo-6- [1- (3, 5-difluorophenyl) ethoxy ] -2-methylpyridin-3-yl } -N-ethyl-N-methyliminocarboxamide, (1.081) Ipfentifluconazole.
2) Inhibitors of respiratory chain complex I or II, for example (2.001) benzovindiflupyr (benzovindiflupyr), (2.002) bixafen (bixafen), (2.003) boscalid (boscald), (2.004) carboxin (carboxin), (2.005) fluopyram (fluopyram), (2.006) flutolanil (flutolanil), (2.007) fluxapyroxad, (2.008) furametpyr), (2.009) thienylazone (isoflutam), (2.010) naphthyridine (isopyrazam) (trans epimer 1R, 4S, 9S), (2.011) naphthyridine (trans epimer 1S, 4R, 9R), (2.012) naphthyridine (trans epimer 1RS, 4 RS, 9S), (SR 1, 9RS 4 RS, SR 4 RS, 9SR mixture), (2.014) isopyrazam (cis epimer 1R, 4S, 9R), (2.015) isopyrazam (cis epimer 1S, 4R, 9S), (2.016) isopyrazam (cis epimer 1RS, 4SR, 9RS), (2.017) penflufen (2.018) penthiopyrad (penthiopyrad), (2.019) pydiflumetofen (pydiflumetofen), (2.020) Pyraziflumid, (2.021) sedaxylamine (sedaxane), (2.022)1, 3-dimethyl-N- (1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl) -1H-pyrazole-4-carboxamide, (2.023)1, 3-dimethyl-N- [ (3R) -1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl ] -1H-pyrazole-4-carboxamide, (2.024)1, 3-dimethyl-N- [ (3S) -1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl ] -1H-pyrazole-4-carboxamide, (2.025) 1-methyl-3- (trifluoromethyl) -N- [ 2' - (trifluoromethyl) biphenyl-2-yl ] -1H-pyrazole-4-carboxamide, (2.026) 2-fluoro-6- (trifluoromethyl) -N- (1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl) benzamide, (2.027)3- (difluoromethyl) -1-methyl-N- (1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl) -1H-pyrazole-4-carboxamide, (2.028)3- (difluoromethyl) -1-methyl-N- [ (3R) -1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl ] -1H-pyrazole-4-carboxamide, (2.029)3- (difluoromethyl) -1-methyl-N- [ (3S) -1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl ] -1H-pyrazole-4-carboxamide, (2.030) Fluindapyr, (2.031)3- (difluoromethyl) -N- [ (3R) -7-fluoro-1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl ] -1-methyl-1H-pyrazole-4-carboxamide, (2.032)3- (difluoromethyl) -N- [ (3S) -7-fluoro-1, 1, 3-trimethyl-2, 3-dihydro-1H-inden-4-yl ] -1-methyl-1H-pyrazole-4-carboxamide, (2.033)5, 8-difluoro-N- [2- (2-fluoro-4- { [4- (trifluoromethyl) pyridin-2-yl ] oxy } phenyl) ethyl ] quinazolin-4-amine, (2.034) N- (2-cyclopentyl-5-fluorobenzyl) -N-cyclopropyl-3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.035) N- (2-tert-butyl-5-methylbenzyl) -N-cyclopropyl-3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.036) N- (2-tert-butylbenzyl) -N-cyclopropyl-3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.037) N- (5-chloro-2-ethylbenzyl) -N-cyclopropyl-3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.038) isoflurypram, (2.039) N- [ (1R, 4S) -9- (dichloromethylene) -1, 2, 3, 4-tetrahydro-1, 4-methanonaphthalene (methanoapthalen) -5-yl ] -3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxamide, (2.040) N- [ (1S, 4R) -9- (dichloromethylene) -1, 2, 3, 4-tetrahydro-1, 4-methanonaphthalen-5-yl ] -3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxamide, (2.041) N- [1- (2, 4-dichlorophenyl) -1-methoxypropan-2-yl ] -3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxamide, (2.042) N- [ 2-chloro-6- (trifluoromethyl) benzyl ] -N-cyclopropyl-3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.043) N- [ 3-chloro-2-fluoro-6- (trifluoromethyl) benzyl ] -N-cyclopropyl-3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole 4-carboxamide, (2.044) N- [ 5-chloro-2- (trifluoromethyl) benzyl ] -N-cyclopropyl-3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.045) N-cyclopropyl-3- (difluoromethyl) -5-fluoro-1-methyl-N- [ 5-methyl-2- (trifluoromethyl) benzyl ] -1H-pyrazole-4-carboxamide, (2.046) N-cyclopropyl-3- (difluoromethyl) -5-fluoro-N- (2-fluoro-6-isopropylbenzyl) -1-methyl-1H-pyrazole-4-carboxamide, (2.047) N-cyclopropyl-3- (difluoromethyl) -5-fluoro-N- (2-isopropyl-5-methylbenzyl) -1-methyl-1H-pyrazole-4-carboxamide, (2.048) N-cyclopropyl-3- (difluoromethyl) -5-fluoro-N- (2-isopropylbenzyl) -1-methyl-1H-pyrazole-4-carbothiocarboxamide, (2.049) N-cyclopropyl-3- (difluoromethyl) -5-fluoro- N- (2-isopropylbenzyl) -1-methyl-1H-pyrazole-4-carboxamide, (2.050) N-cyclopropyl-3- (difluoromethyl) -5-fluoro-N- (5-fluoro-2-isopropylbenzyl) -1-methyl-1H-pyrazole-4-carboxamide, (2.051) N-cyclopropyl-3- (difluoromethyl) -N- (2-ethyl-4, 5-dimethylbenzyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.052) N-cyclopropyl-3- (difluoromethyl) -N- (2-ethyl-5-fluorobenzyl) -5-fluoro-1-methyl-4-carboxamide -1H-pyrazole-4-carboxamide, (2.053) N-cyclopropyl-3- (difluoromethyl) -N- (2-ethyl-5-methylbenzyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.054) N-cyclopropyl-N- (2-cyclopropyl-5-fluorobenzyl) -3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.055) N-cyclopropyl-N- (2-cyclopropyl-5-methylbenzyl) -3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.056) N-cyclopropyl-N- (2-cyclopropylbenzyl) -3- (difluoromethyl) -5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.057) pyrapropofol.
3) Inhibitors of respiratory chain complex III, such as (3.001) ametoctradin (ametoctradin), (3.002) ametryn (amisulbactam), (3.003) azoxystrobin (azoxystrobin), (3.004) tolutrobin (coumethoxyystron), (3.005) coumoxystrobin (coumoxystrobin), (3.006) cyazofamid, (3.007) dimoxystrobin, (3.008) enestrobin (enoxytrobin), (3.009) famoxadone (famoxadone), (3.010) fenamidone (fenaminozone), (3.011) flufenoxystrobin (flufenoxystrobin), (3.012) fluoxystrobin (fluoxystrobin), (3.013) kresoxim-metystrobin (kresoxim-methyl-dystrobin), (3.014) fluoxystrobin (fluoxystrobin) (3.2) fluoxystrobin (fluoxystrobin), (3.014) (fluoxystrobin) (3.2) fluoxystrobin (fluoxystrobin), (3.11, fluoxystrobin) (3.11, fluoxystrobin) (fludioxonil) (fluoxystrobin) (3.11, fludioxonil) (3.11) fludioxonil) (3.11) fludioxonil) (3.11) fludioxonil) (flutrobin) (fludioxonil) (3.11) flutrobin) (fludioxonil) (3.11) fludioxonil) (3.11) fludioxonil) (flutrobin) (fludioxonil) (3.11) fludioxonil) (3.11) fludioxonil) (3.11.11) fludioxonil) (3.11) fludioxonil) (3.11.11) fludioxonil) (3.11) fludioxonil) (3.11) fludioxonil) (3.8.8.11) fludioxonil) (3.8.11.8.8) 2-Phenylethenyl ] oxy } phenyl) ethylidene ] amino } oxy) methyl ] phenyl } -2- (methoxyimino) -N-methylacetamide, (3.022) (2E, 3Z) -5- { [1- (4-chlorophenyl) -1H-pyrazol-3-yl ] oxy } -2- (methoxyimino) -N, 3-dimethylpent-3-enamide, (3.023) (2R) -2- {2- [ (2, 5-dimethylphenoxy) methyl ] phenyl } -2-methoxy-N-methylacetamide, (3.024) (2S) -2- {2- [ (2, 5-dimethylphenoxy) methyl ] phenyl } -2-methoxy-N-methylacetamide, methyl-2- (methoxyimino) -N-methylacetamide, methyl-2-methoxy-N-methylacetamide, methyl-2-amino-2- (methoxyimino) -N-methylacetamide, methyl-2-methyl-acetamide, 3.023, (3.025) (3S, 6S, 7R, 8R) -8-benzyl-3- [ ({3- [ (isobutyryloxy) methoxy ] -4-methoxypyridin-2-yl } carbonyl) amino ] -6-methyl-4, 9-dioxo-1, 5-dioxononane (dioxanan) -7-yl 2-methylpropionate, (3.026) mandestrobin, (3.027) N- (3-ethyl-3, 5, 5-trimethylcyclohexyl) -3-carboxamido-2-hydroxybenzamide, (3.028) (2E, 3Z) -5- { [1- (4-chloro-2-fluorophenyl) -1H-pyrazol-3-yl ] oxy } -2- (methoxyimino) -N, 3-dimethylpent-3-enamide, methyl (3.029) {5- [3- (2, 4-dimethylphenyl) -IH-pyrazol-1-yl ] -2-methylbenzyl } carbamate, (3.030) metyltetrapole, (3.031) florylpicoxamide.
4) Mitotic and cell-division inhibitors, for example (4.001) carbendazim (carbendazim), (4.002) diethofencarb (diethofencarb), (4.003) ethaboxam (ethaboxam), (4.004) fluopicolide (fluopicolide), (4.005) pencycuron (pencycuron), (4.006) thiabendazole (thiabendazole), (4.007) thiophanate-methyl (thiophanate-methyl), (4.008) zoxamide (zoxamide), (4.009) 3-chloro-4- (2, 6-difluorophenyl) -6-methyl-5-phenylpyridazine, (4.010) 3-chloro-5- (4-chlorophenyl) -4- (2, 6-difluorophenyl) -6-methylpyridazine, (4.011) 3-chloro-5- (6-chloropyridin-3-yl) -6-methyl-4- (2, 4, 6-trifluorophenyl) pyridazine, (4.012)4- (2-bromo-4-fluorophenyl) -N- (2, 6-difluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.013)4- (2-bromo-4-fluorophenyl) -N- (2-bromo-6-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.014)4- (2-bromo-4-fluorophenyl) -N- (2-bromophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.015)4- (2-bromo-4-fluorophenyl) -N- (2-chloro-6-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.016)4- (2-bromo-4-fluorophenyl) -N- (2-chlorophenyl) -1, 3-dimethyl-IH-pyrazol-5-amine, (4.017)4- (2-bromo-4-fluorophenyl) -N- (2-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.018)4- (2-chloro-4-fluorophenyl) -N- (2, 6-difluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.019)4- (2-chloro-4-fluorophenyl) -N- (2-chloro-6-fluorobenzene) -yl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.020)4- (2-chloro-4-fluorophenyl) -N- (2-chlorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.021)4- (2-chloro-4-fluorophenyl) -N- (2-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.022)4- (4-chlorophenyl) -5- (2, 6-difluorophenyl) -3, 6-dimethylpyridazine, (4.023) N- (2-bromo-6-fluorophenyl) -4- (2-chloro-4-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.024) N- (2-bromophenyl) -4- (2-chloro-4-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine, (4.025) N- (4-chloro-2, 6-difluorophenyl) -4- (2-chloro-4-fluorophenyl) -1, 3-dimethyl-1H-pyrazol-5-amine.
5) Compounds capable of multidot action, such as (5.001) Bordeaux mix (Bordeaux mix), (5.002) captafol, (5.003) captan (captan), (5.004) chlorothalonil (chlorothalonil), (5.005) cupric hydroxide, (5.006) cupric naphthenate (copperphenate), (5.007) cupric oxide, (5.008) cupric oxychloride (copperoxolide), (5.009) cupric sulfate (2+), (5.010) dithianon (dithianon), (5.011) dodidine, (5.012) folpet (folpet), (5.013) mancozeb (mancob), (5.014) maneb (5.015) metiram (metiram), (5.016) zinoz (metiram) (7) quinoline (conazol) (355.5635) and (propineb) (36020) propineb (3645) and (propineb) (5.021) zinc polysulfate, including propineb (propineb) (5.016), (5.023) 6-ethyl-5, 7-dioxo-6, 7-dihydro-5H-pyrrolo [3 ', 4': 5, 6] [1, 4] dithiino [2, 3-c ] [1, 2] thiazole-3-carbonitrile.
6) Compounds capable of inducing host defenses, for example (6.001) acibenzolar-S-methyl, (6.002) isotianil, (6.003) probenazole, (6.004) tiadinil).
7) Inhibitors of amino acid and/or protein biosynthesis, for example (7.001) cyprodinil (cyprodinil), (7.002) kasugamycin (kasugamycin), (7.003) kasugamycin hydrochloride hydrate, (7.004) oxytetracycline (oxytetracycline), (7.005) pyrimethanil, (7.006)3- (5-fluoro-3, 3, 4, 4-tetramethyl-3, 4-dihydroisoquinolin-1-yl) quinoline.
8) Inhibitors of ATP production, for example (8.001) silthiofam (silthiofam).
9) Cell wall synthesis inhibitors, for example (9.001) benthiavalicarb (benthiavalicarb), (9.002) dimethomorph, (9.003) flumorph (flumorph), (9.004) iprovalicarb, (9.005) mandipropamid (maninparamide), (9.006) pyrimorph (pyrimorph), (9.007) valienamine (valifenate), (9.008) (2E) -3- (4-tert-butylphenyl) -3- (2-chloropyridin-4-yl) -1- (morpholin-4-yl) prop-2-en-1-one, (9.009) (2Z) -3- (4-tert-butylphenyl) -3- (2-chloropyridin-4-yl) -1- (morpholin-4-yl) prop-2-en-1-one.
10) Lipid and membrane synthesis inhibitors, for example (10.001) propamocarb (propamocarb), (10.002) propamocarb hydrochloride (propamocarb hydrochloride), (10.003) tolclofos-methyl.
11) Melanin biosynthesis inhibitors such as (11.001) tricyclazole, (11.002)2, 2, 2-trifluoroethyl { 3-methyl-1- [ (4-methylbenzoyl) amino ] but-2-yl } carbamate.
12) Nucleic acid synthesis inhibitors, for example (12.001) benalaxyl (benalaxyl), (12.002) high efficiency benalaxyl (benalaxyl-M) (kiralaxyl), (12.003) metalaxyl (metalaxyl), (12.004) high efficiency metalaxyl (metalaxyl-M) (mefenoxam).
13) Signal transduction inhibitors, for example (13.001) fludioxonil (fludioxonil), (13.002) iprodione (iprodione), (13.003) procymidone (procymidone), (13.004) proquinazid (proquinazid), (13.005) quinoxyfen (quinoxyfen), (13.006) vinclozolin (vinclozolin).
14) Compounds capable of acting as uncouplers, for example (14.001) fluazinam, (14.002) meptyldinocap.
15) Other compounds, for example (15.001) Abscisic acid (Abscisic acid), (15.002) thiocyanobenzene (benthiazole), (15.003) betaxazine, (15.004) carbapenem (capsomycin), (15.005) carvone (carvone), (15.006) chlorfenapyr (chinomethionat), (15.007) thiabendazole (cufraneb), (15.008) cyflufenamid (15.009) cyromazine, (15.010) cyclopropanesulfonamide (cyosulfamide), (15.011) fluvalinil, (15.012) fosetyl-aluminum (fosetyl-aliminium), (15.013) calcium fosetyl-calceium, (48) sodium fosetyl-sodium (fosetyl-sodium), (15.015) methyl isothiocyanate (cyathomycin acetate), (3829) nickel dithiocarbamate (cartioxybenzoate), (15.021) thiocyanine (dimethyldithiocarbamate), (15.018) dithiofenamate (dithiofenamate), (15.018) thiocyanine (dimethyldithiocarbamate (dithiofenamate), (15.018) dithiofenapyr-15.018), (15.022) Fluorothiazolepyriprole (oxathiapigenin), (15.023) Oxyfenthin, (15.024) pentachlorophenol and its salts, (15.025) phosphorous acid and its salts, (15.026) propamocarb-fosetylate, (15.027) pyriofenone, (chlazofenone), (15.028) isobutoxyquinoline (tebufloquin), (15.029) phyllokupflug (tecloftalam), (15.030) Trifluanide, (15.031)1- (4- {4- [ (5R) -5- (2, 6-difluorophenyl) -4, 5-dihydro-1, 2-oxazol-3-yl ] -1, 3-thiazol-2-yl } piperidin-1-yl) -2- [ 5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl ] 15.032)1- (4- {4- [ (5S) -5- (2), 6-difluorophenyl) -4, 5-dihydro-1, 2-oxazol-3-yl ] -1, 3-thiazol-2-yl } piperidin-1-yl) -2- [ 5-methyl-3- (trifluoromethyl) -1H-pyrazol-1-yl ] ethanone, (15.033)2- (6-benzylpyridin-2-yl) quinazoline, (15.034) dipyrmetitrone, (15.035)2- [3, 5-bis (difluoromethyl) -1H-pyrazol-1-yl ] -1- [4- (4- {5- [2- (prop-2-yn-1-yloxy) phenyl ] -4, 5-dihydro-1, 2-oxazol-3-yl } -1, 3-thiazol-2-yl) piperidin-1-yl ] ethanone, (15.036)2- [3, 5-bis (difluoromethyl) -1H-pyrazol-1-yl ] -1- [4- (4- {5- [ 2-chloro-6- (prop-2-yn-1-yloxy) phenyl ] -4, 5-dihydro-1, 2-oxazol-3-yl } -1, 3-thiazol-2-yl) piperidin-1-yl ] ethanone, (15.037)2- [3, 5-bis (difluoromethyl) -1H-pyrazol-1-yl ] -1- [4- (4- {5- [ 2-fluoro-6-, ( Prop-2-yn-1-yloxy) phenyl ] -4, 5-dihydro-1, 2-oxazol-3-yl } -1, 3-thiazol-2-yl) piperidin-1-yl ] ethanone, (15.038)2- [6- (3-fluoro-4-methoxyphenyl) -5-methylpyridin-2-yl ] quinazoline, (15.039)2- { (5R) -3- [2- (1- { [3, 5-bis (difluoromethyl) -1H-pyrazol-1-yl ] acetyl } piperidin-4-yl) -1, 3-thiazol-4-yl ] -4, 5-dihydro-1, 2-oxazol-5-yl } -3-chlorophenyl methanesulfonate, (15.040)2- { (5S) -3- [2- (1- { [3, 5-bis (difluoromethyl) -1H-pyrazol-1-yl ] acetyl } piperidin-4-yl) -1, 3-thiazol-4-yl ] -4, 5-dihydro-1, 2-oxazol-5-yl } -3-chlorophenyl methanesulfonate, (15.041) Iflufenoquin, (15.042)2- { 2-fluoro-6- [ (8-fluoro-2-methylquinolin-3-yl) oxy ] phenyl } propan-2-ol, (15.043)2- {3- [2- (1- { [3, 5-bis (difluoromethyl) -1H-pyrazol-1-yl ] acetyl } piperidin-4-yl) -1, 3-thiazol-4-yl ] -4, 5-dihydro-1, 2-oxazol-5-yl } -3-chlorophenyl methanesulfonate, (15.044)2- {3- [2- (1- { [3, 5-bis (difluoromethyl) -1H-pyrazol-1-yl ] acetyl } piperidin-4-yl) -1, 3-thiazol-4-yl ] -4, 5-dihydro-1, 2-oxazol-5-yl } phenylmethanesulfonate, (15.045) 2-phenylphenol and salts thereof, (15.046)3- (4, 4, 5-trifluoro-3, 3-dimethyl-3, 4-dihydroisoquinolin-1-yl) quinoline, (15.047) quinofumelin, (15.048) 4-amino-5-fluoropyrimidin-2-ol (tautomeric form: 4-amino-5-fluoropyrimidin-2 (1H) -one), (15.049) 4-oxo-4- [ (2-phenylethyl) amino ] butanoic acid, (15.050) 5-amino-1, 3, 4-thiadiazole-2-thiol, (15.051) 5-chloro-N '-phenyl-N' - (prop-2-yn-1-yl) thiophene-2-sulfonylhydrazide, (15.052) 5-fluoro-2- [ (4-fluorobenzyl) oxy ] pyrimidin-4-amine, (15.053) 5-fluoro-2- [ (4-methylbenzyl) oxy ] pyrimidin-4-amine, (15.054) 9-fluoro-2, 2-dimethyl-5- (quinolin-3-yl) -2, 3-dihydro-1, 4-benzoxazepin (benzoxazepine), (15.055) but-3-yn-1-yl {6- [ ({ [ (Z) - (1-methyl-1H-tetrazol-5-yl) (phenyl) methylidene ] amino } oxy) methyl ] pyridin-2-yl } carbamate, ethyl (15.056) (2Z) -3-amino-2-cyano-3-phenylacrylate, (15.057) phenazine-1-carboxylic acid, (15.058) propyl 3, 4, 5-trihydroxybenzoate, (15.059) quinolin-8-ol, (15.060) quinolin-8-ol sulfate (2: 1), (15.061) {6- [ ({ [ (1-methyl-1H-tetrazol-5-yl) (phenyl) methylidene ] amino } oxy) methyl ] pyri-dine Pyridin-2-yl } carbamic acid tert-butyl ester, (15.062) 5-fluoro-4-imino-3-methyl-1- [ (4-methylphenyl) sulfonyl ] -3, 4-dihydropyrimidin-2 (1H) -one, (15.063) aminopyrifen.
All named mixed compatibilisers of classes (1) to (15) as described above may be present as free compounds and/or, if their functional groups allow, as agriculturally acceptable salts thereof.
The compounds and compositions of formula (I) may also be combined with one or more biological control agents.
Examples of biological control agents that can be combined with the compounds of formula (I) and compositions comprising the same are:
(A) an antibacterial agent selected from the group consisting of：
(A1) Bacteria, such as (A1.1) Bacillus subtilis, in particular the strain QST713/AQ713 (obtainable from Bayer Crop science LP, US as SERENDE OPTI or SERENDE ASO, NRRL accession No. B21661 and described in U.S. Pat. No. 6,060,051)In (1); (A1.2) Bacillus amyloliquefaciens, in particular strain D747 (available from Certis, US as Double Nickel)TMObtained, accession number FERM BP-8234 and disclosed in U.S. patent No. 7,094,592); (A1.3) Bacillus pumilus (Bacillus pumilus), in particular strain BU F-33(NRRL accession number 50185); (A1.4) Bacillus subtilis amyloliquefaciens strain FZB24 (available from Novozymes. US asObtaining); (A1.5) a Paenibacillus sp strain with accession number NRRL B-50972 or accession number NRRL B-67129 and described in International patent publication No. WO 2016/154297; and
(A2) Fungi, such as (a2.1) Aureobasidium pullulans (Aureobasidium pullulans), in particular blastospores of the strain DSM 14940; (a2.2) a budding spore of aureobasidium pullulans strain DSM 14941; (a2.3) a mixture of blastospores of a. pullulans, in particular of the strains DSM14940 and DSM 14941;
(B) a fungicide selected from the group consisting of:
(B1) bacteria, such as (B1.1) Bacillus subtilis, in particular strain QST713/AQ713 (obtainable from Bayer Crop science LP, US as SERENDE OPTI or SERENDE ASO, NRRL accession No. B21661 and described in U.S. Pat. No. 6,060,051); (B1.2) Bacillus pumilus, in particular the strain QST2808 (available from Bayer crop science LP, US, for exampleObtained, accession number NRRL B-30087 and described in U.S. patent No. 6,245,551); (B1.3) Bacillus pumilus, in particular strain GB34 (available from Bayer AG, DE as Yield)Obtaining); (B1.4) bacillus pumilus, in particular strain BU F-33(NRRL accession No. 50185); (B1.5) Bacillus amyloliquefaciens, in particular strain D747 (available from Certis, US as Double Nickel)TMObtained under accession number FERM BP-8234 and disclosed in U.S. Pat. No. 5National patent No. 7,094,592); (B1.6) Bacillus subtilis Y1336 (available from Bio-Tech, Taiwan and WP obtained, registered as a biological fungicide in taiwan under accession numbers 4764, 5454, 5096 and 5277); (B1.7) Bacillus amyloliquefaciens strain MBI 600 (available as SUBTILEX from BASF SE); (B1.8) Bacillus subtilis Strain GB03 (available from Bayer AG, DE andobtaining); (B1.9) Bacillus subtilis amyloliquefaciens strain FZB24 (available from Novozymes Biologicals Inc., Salem, Virginia or Syngenta Crop Protection, LLC, Greensboro, North Carolina as fungicideOrECO acquisition (EPA accession number 70127-5)); (B1.10) Bacillus mycoides, isolate J (obtainable from Certis USA as BmJ TGAI or WG); (B1.11) Bacillus licheniformis (Bacillus licheniformis), especially strain SB3086 (available from Novozymes as EcoGuard (TM) biological fungicides and Green Releaf); (B1.12) a Paenibacillus species strain, accession number NRRL B-50972 or accession number NRRL B-67129 and described in International patent publication No. WO 2016/154297.
In some embodiments, the biocontrol agent is a bacillus subtilis or bacillus amyloliquefaciens strain that produces a fengycin (fengycin) or thujaplicin (plipasatin) -type compound, an iturin-type compound, and/or a surfactin-type compound. For background, see the following review articles: oncogene, m, et al, "Bacillus lipids: versatile Weapons for Plant Disease Biocontrol, "Trends in Microbiology, Vol.16, No. 3, month 3 2008, p.115-. The Bacillus strain capable of producing lipopeptides includes Bacillus subtilis QST713 (Bacillus subtilis) Obtained from Bayer crop science LP, US as SERENDE OPTI or SERENDE ASO, NRRL accession No. B21661 and described in U.S. Pat. No. 6,060,051), Bacillus amyloliquefaciens strain D747 (available from Certis, US as Double Nickel)TMObtained, accession number FERM BP-8234 and disclosed in U.S. patent No. 7,094,592); bacillus subtilis MBI600 (available from Becker Underwood, US and so on)Obtained, EPA accession number 71840-8); bacillus subtilis Y1336 (available from Bio-Tech, Taiwan and Inc.)WP obtained, registered as a biological fungicide in taiwan under accession numbers 4764, 5454, 5096 and 5277); bacillus amyloliquefaciens, in particular strain FZB42 (available from ABiTEP, DE and others)Obtaining); and Bacillus subtilis amylolytic variant FZB24 (available from Novozymes Biologicals Inc., Salem, Virginia or Syngenta Crop Protection, LLC, Greensboro, North Carolina as fungicidesOrECO acquisition (EPA accession number 70127-5)); and
(B2) fungi, for example: (B2.1) Coniothyrium minitans, in particular the strain CON/M/91-8 (accession number DSM-9660; e.g.from Bayer)) (ii) a (B2.2) Saccharomyces coreana (Metschnikowia fructicola), in particular strain NRRL Y-30752 (for example)) (ii) a (B2.3) Microphaenopsis ochracea (e.g. from P) Of rophyta) (ii) a (B2.5) Trichoderma species (Trichoderma spp.), including Trichoderma atroviride (Trichoderma atroviride), strain SC1 described in international publication No. PCT/IT 2008/000196; (B2.6) Trichoderma harzianum rifai Strain KRL-AG2 (also referred to as strain T-22,/ATCC 208479, e.g., PLANTSHIELD T-22G, available from BioWorks, US,And turkshield); (B2.14) Gliocladium roseum (Gliocladium roseum), strain 321U, available from w.f. stoneman Company LLC; (B2.35) yellow blueish (Talaromyces flavus), strain V117B; (B2.36) Trichoderma asperellum (Trichoderma asperellum), strain ICC 012, available from Isagro; (B2.37) Trichoderma asperellum, Strain SKT-1 (e.g., available from Kumiai Chemical Industry)) (ii) a (B2.38) Trichoderma atroviride, Strain CNCM I-1237 (e.g. from Agrauxine, FR)WP); (B2.39) trichoderma aureoviride, strain No. V08/002387; (B2.40) trichoderma atroviride, strain NMI No. V08/002388; (B2.41) trichoderma atroviride, strain NMI No. V08/002389; (B2.42) trichoderma atroviride, strain NMI No. V08/002390; (B2.43) Trichoderma atroviride, strain LC52 (e.g. Tenet supplied by Agrimem Technologies Limited); (B2.44) trichoderma atroviride, strain ATCC 20476(IMI 206040); (B2.45) Trichoderma atroviride, strain T11(IMI352941/CECT 20498); (B2.46) Trichoderma hamatum; (B2.47) Trichoderma harzianum (Trichoderma harzianum); (B2.48) Trichoderma harzianum T39 (e.g., available from Makhteshim, US) ) (ii) a (B2.49) Trichoderma harzianum, in particular strain KD (e.g.Trichoplus (available from Becker Underwood) from Biological Control Products, SA); (B2.50) Trichoderma harzianum, Strain ITEM 908 (e.g.Trianum-P from Koppert); (B2.51) trichoderma harzianum, strain TH35 (e.g. Root-Pro supplied by Mycontrol); (B2.52) Trichoderma virens (Trichoderma virens) (also known as Gliocladium virens), in particular strain GL-21 (e.g. soligard 12G supplied by Certis, US); (B2.53) Trichoderma viride (Trichoderma viride), strain TV1 (e.g. Trianum-P supplied by Koppert); (B2.54) Erysiphe cichoracearum (Ampelomyces quisqualis), in particular the strain AQ 10 (e.g. AQ supplied by IntrachemBio Italia)) (ii) a (B2.56) a blastospore of a. pullulans, in particular of the strain DSM 14940; (B2.57) a blastospore of a. pullulans, in particular of the strain DSM 14941; (B2.58) A mixture of Brevibacterium sp, in particular the blastospores of the strains DSM14940 and DSM 14941 (for example as supplied by bio-ferm, CH)) (ii) a (B2.64) Acremonium cladosporioides (Cladosporium cladosporioides), strain H39 (supplied by Stichting Dienst Landbowklung Onderzoek); (B2.69) Gliocladium catenulatum (Gliocladium catenulatum) (synonyms: Clinostacchys rosea f. catenulate) strain J1446 (provided, for example, by AgBio Inc And provided by Kemira Agro Oy, for example) (ii) a (B2.70) conidia of Verticillium lecanii (formerly known as Verticillium lecanii) strain KV01 (e.g., supplied by Koppert/Arysta)) (ii) a (B2.71) Penicillium helminthium (Penicillium vernulatum); (B2.72) Pichia anomala (Pichia anomala), Strain WRL-076(NRRL Y-30842); (B2.75) Trichoderma atroviride, strain SKT-1(FERM P-16510); (B2.76) Trichoderma atroviride, Strain SKT-2(FERM P-1)6511) (ii) a (B2.77) Trichoderma atroviride, strain SKT-3(FERM P-17021); (B2.78) Trichoderma gamsii (Trichoderma gamsii) (formerly Trichoderma viride), strain ICC080(IMI CC 392151 cab, e.g. BioDerma supplied by AGROBIOSOL DE MEXICO, s.a.de c.v.); (B2.79) Trichoderma harzianum, strain DB 103 (e.g.T-Gro 7456 supplied by Datutat Biolab); (B2.80) Trichoderma polyspora (Trichoderma polyspora), strain IMI 206039 (e.g., Binab TF WP supplied by BINAB Bio-Innovation AB, Sweden); (B2.81) Trichoderma stromatum (e.g. Tricovab supplied by Ceplac, Brazil); (B2.83) Ullmann's disease, in particular strain HRU3 (e.g. as supplied by Botry-Zen Ltd, NZ) ) (ii) a (B2.84) Verticillium albo-atrum (formerly Verticillium dahliae), strain WCS850(CBS 276.92; e.g., Dutch Trig supplied by Tree Care Innovations); (B2.86) Verticillium chlamydosporia (Verticillium chlamydosporium); (B2.87) mixture of Trichoderma asperellum strain ICC 012 and Trichoderma gamsii strain ICC 080 (e.g., available from Bayer Crop science LP, US as BIO-TAM)TMThe product of (1).
Further examples of biological control agents that can be combined with the compounds of formula (I) and compositions comprising the same are:
a bacterium selected from the group consisting of: bacillus cereus (Bacillus cereus), particularly Bacillus cereus strain CNCM I-1562 and Bacillus firmus (Bacillus firmus), strain I-1582 (accession number CNCM I-1582), Bacillus subtilis strain OST 30002 (accession number NRRL B-50421), Bacillus thuringiensis (Bacillus thuringiensis), particularly Bacillus thuringiensis subspecies israelensis (B.thuringiensis subspecies israelensis) (serotype H-14), strain AM65-52 (accession number ATCC 1276), Bacillus thuringiensis subspecies silcalifornica (B.Thingiensis subsp.stazawai), particularly strain ABTS-1857(SD-1372), Bacillus thuringiensis subspecies kushikuchi (B.Thigiensis subsp.kuriki) strain HD-1, Bacillus thuringiensis subspecies B (Bacillus subtilis) strain SD-1372), Bacillus thuringiensis subspecies basilica (B.Thikiensis subspecies sp.176), Bacillus thuringiensis subspecies natriensis strain Rodentis sp.176 (Roxiella typhi), Bacillus thuringiensis subspecies strain Roxitorius strain Roxiella sp.176 (Roxiella typhi), strain Roxitorius sp.176. sp.sp.sp. PR3 (accession number ATCC SD-5834), Streptomyces microflavus strain AQ6121(═ QRD 31.013, NRRL B-50550), and Streptomyces Bright flavus (Streptomyces galbus) strain AQ 6047 (accession number NRRL 30232);
Fungi and yeasts selected from the group consisting of: beauveria bassiana (Beauveria bassiana), in particular the strain ATCC 74040; lecanicillium spp, in particular strain HRO LEC 12; metarhizium anisopliae (Metarhizium anisopliae), particularly strain F52(DSM3884 or ATCC 90448); paecilomyces fumosoroseus (now: Isaria fumosorosea), in particular strain IFPC 200613 or strain Apopka 97 (accession number ATCC 20874); and Paecilomyces lilacinus (Paecilomyces lilacinus), particularly Paecilomyces lilacinus strain 251(AGAL 89/030550);
a virus selected from the group consisting of: spodoptera fusca (Adoxophycochines orana) (summer fruit leafroller) Granulosis Virus (GV), apple peel diamondback moth (codling moth) Granulosis Virus (GV), Helicoverpa armigera (cotton bollworm) Nucleopolyhedrovirus (NPV), Spodoptera exigua (Beet armyworm) mNPV, Spodoptera frugiperda (Spodoptera frugiperda) (fall armyworm) mNPV, and Spodoptera littoralis (African cottonleaf worm) (Africa cotton leafroller) NPV.
Bacteria and fungi that can be added to plants or plant parts or plant organs as "inoculants" and promote plant growth and plant health by virtue of their specific characteristics. Examples are: agrobacterium sp, nitrorhizobium rhizomae (Azorhizobium caudolans), Azotobacter sp, Chroorhizobium sp, Burkholderia sp, in particular Burkholderia cepacia (Burkholderia cepacia) (formerly Pseudomonas cepacia), Gigartina sp or Gigaspora wax, Glomus sp, Lacchacia sp, lactobacillus buchneri (Lactobacillus buchneri), Gliocladium species (Paraglomus spp.), Pisolithus tinctorus, Pseudomonas species (Pseudomonas spp.), Rhizobium species (Rhizobium spp.), especially Rhizobium trifolium (Rhizobium trifolii), Rhizopus species (Rhizopgon spp.), Scleroderma spp., Lactobacillus spp., and Streptomyces species (Streptomyces spp.).
Plant extracts and products formed by microorganisms, including proteins and secondary metabolites, useful as biological control agents, such as garlic (Allium sativum), wormwood (Artemisia absinthium), azadirachtin (azadirachtin), Biokeepers WP, Cassia nigrans, Celastrus angulatus (Celastrus angulus), Chenopodium antalminticum, chitin, Armour-Zen, Dryopteris filix-mas, Equisetum arvense (Equisetum arvense), Fortuneum Aza, Fusariup, Heads Up (Chenopodium saponin extract)), Pyrethrum (Pyrethrum)/pyrethrin, Suzurine (Queria), Quillaia (Quillaia), Quillaia (Quillaja), Quillaja (Quillaja), Reynaudiana ja (Reynaudiana ja), and Quillaja (Reynaudiana) areTMInsecticides ", rotenone (rotenone), ryanodine (ryania)/ryanodine (ryanodine), comfrey (Symphytum officinale), Tanacetum vulgare (Tanacetum vulgare), thymol (thymol), Triact 70, TriCon, tropieullum maju, Urtica dioica (Urtica dioica), veratrine (Veratrin), mistletoe of ginkgo (Viscum album), Brassicaceae (Brassicaceae) extracts (in particular rape or mustard flour).
Examples of insecticides, acaricides and nematicides that can be mixed with the compounds of formula (I) and compositions comprising them, respectively, are:
(1) Acetylcholinesterase (AChE) inhibitors, such as carbamates, e.g. bendiocarb (alanycarb), aldicarb (aldicarb), bendiocarb (benfuracarb), benfuracarb (benfuracarb), butocarb (butocarboxin), butoxycarb (butoxycarb), carbaryl (baryl), carbofuran (carbofuran), carbosulfan (carbosulfan), ethiofencarb (ethiofencarb), fenobucarb (fenocarb), varroate (formiate), furacarb (furathiocarb), isoprocarb (isoprocarb), methiocarb (methiocarb), methomyl (methomyl), methiocarb (oxamyl), pirimicarb (pirimicarb), bendiocarb (propoxycarb), methiocarb (pirimicarb), methiocarb (propoxur), methiocarb (methocarb (XMcarb), and triazocarb (triazamate); or organic phosphoric acid esters such as acephate (acephate), azamethiphos (azamethiphos), ethylthion (azinphos-ethyl), methylthiophos (azinphos-methyl), cadusafos (cadusafos), chlorophenoxyfos (chlorethoxyfos), chlorfenvinphos (chlorfenvinphos), chlorthion (chlorfenapyr), chlorpyrifos (chlorpyrifos-methyl), coumaphos (coumaphos), cyanophos (cyanophos), demeton-S-methyl), diazinon (diazinon), dichlorvos (dichlorvos)/DDVP, chlorothos (dicrotophos), dimethoate (dimethofos), methidafenphos (dimethion), ethiofenphos (ethiophos), thiophosphoryl (isopropyl), thiophosphoryl (ethiophos), thiofenthion (isopropyl), thion (ethiophos), thion (isopropyl, thiofenthion (ethiophos), thiofenthion (isopropyl), thiobenzofos (isopropyl, thiobenzothiobenzofos), thiobenzofos (isopropyl, thiobenzothiobenzothiobenzothiobenzofos), thiobenzothiobenzothiobenzofos (isopropyl, thiobenzothiobenzothiobenzothiobenzothion (isopropyl, thiobenzothiobenzothion (isopropyl-methyl, thion), thion (isopropyl-thion, thiobenzothiobenzothion, thion, thiobenzothion, thion, thiobenzothion-methyl, thion, thio, Isoxazolyl phosphine (isoxathion), malathion (malathion), triazophos (mecarbam), methamidophos (methamidophos), methidathion (methidathion), mepinylphos (mevinphos), monocrotophos (monocrotophos), naled (naled), omethoate (omethoate), oxydemethofos (oxydemethon-methyl), parathion-methyl (parathion-methyl), phenthoate (phenthoate), phorate (phosphate), phosmet (phos), phosmet (phospho), phosphamide (phosphamidon), phoxim (phoxim), pirimiphos-methyl (pirimiphos-methyl), profenofos (profenofos), pyriproxyfen (propetamps), prothiochion (prothiofos), pyraclofos (pyraclofos), pyridaphenthion (pyridaphenthion), quinalphos (quinalphos), sulfotep (sulfotep), butylpyrimidine phos (terbipimfos), temephos (temephos), terbufos (terbufos), tetrachlorvinphos (tetrachlorovinphos), methamidophos (thiomethoxone), triazophos (triazophos), trichlorfon (trichlorfon), and aphidicolin (vamidothion).
(2) GABA-gated chloride channel blockers, such as cyclopentadiene organochlorines, e.g. chlordane (chlordane) and endosulfan (endosulfan), or phenylpyrazoles (fiproles), e.g. ethiprole (ethiprole) and fipronil (fipronil).
(3) Sodium channel modulators, such as pyrethroids, e.g., bifenthrin (acrinathrin), allethrin (allethrin), d-cis-trans allethrin, d-trans allethrin, bifenthrin (bifenthrin), bioallethrin (bioallethrin), bioallethrin s-cyclopentenyl isomer, bioresmethrin (bioresmethrin), cycloprothrin (cycloprothrin), cyfluthrin (cyfluthrin), beta-cyfluthrin, cyhalothrin (cyhalothrin), lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin (cypermethrin), alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, beta-cypermethrin, cyhalothrin, cyphenothrin [ (1R) -trans-isomer ] (cyphenothrin [ (1R) -trans-isomer zeta-isomer, [ deltamethrin ], cyhalothrin (deltamethrin ]), cyhalothrin (deltamethrin), Prallethrin [ (EZ) - (1R) -isomer ] (empenthrin [ (EZ) - (1R) -isomer ]), cis-cyhalothrin (esfenvalenate), ethofenprox (etofenprox), fenpropathrin (fenpropathrin), fenvalerate (fenvalenate), flucythrinate (fluythrinate), flumethrin (flumethrin), tau-fluvalinate (tau-fluvalinate), benzofenapyr (halfenprox), imiprothrin (improtrin), thiaclopramide (kadethrin), momfluorothrin, permethrin (permethrin), phenothrin [ (1R) -trans-isomer ] (phenothrin [ (1R) -trans-isr ]), prallethrin (prallethrin), pyrethrin (pyrrethrins) (permethrin) ], tefluthrin (fluthrin), tefluthrin (tefluthrin), tefluthrin (fluthrin), fluthrin (fluthrin), fluthrin) (fluthrin), fluthrin (fluthrin), fluthrin (fluthrin, flu, Tetrabromthrin and transfluthrin, or dichlorodiphenyl trichloroethane (DDT), or dichlorodiphenyl trichloroethane (methoxychlor).
(4) Nicotinic acetylcholine receptor (nAChR) competitive modulators, such as neonicotinoids (neonicotinoids), for example acetamiprid (acetamiprid), clothianidin (clothianidin), dinotefuran (dinotefuran), imidacloprid (imidacloprid), nitenpyram (nitenpyram), thiacloprid (thiacloprid) and thiamethoxam (thiamethoxam), or nicotine (nicotinine), or sulfoxaflor (sulfoxaflor), or flurpyridinon (flupyradifurone).
(5) Nicotinic acetylcholine receptor (nAChR) allosteric modulators, such as spinosyns, e.g., spinetoram (spinetoram) and spinosad (spinosad).
(6) Glutamate-gated chloride channel (GluCl) allosteric modulators, such as avermectins (avermectins)/milbemycins (milbemycins), for example, abamectin (abamectin), emamectin benzoate (emamectin benzoate), lepimectin (lepimectin), and milbemectin (milbemectin).
(7) Juvenile hormone mimics, such as juvenile hormone analogs, e.g. methoprene (hydroprene), methoprene (kinoprene) and methoprene (methoprene), or fenoxycarb (fenoxycarb), or pyriproxyfen (pyriproxyfen).
(8) Various non-specific (multi-site) inhibitors, such as alkyl halides, e.g., methyl bromide and other alkyl halides; or chloropicrine or sulfuryl fluoride or borax or tartrazine or methyl isocyanate generating agents such as diazemet and metam (meta).
(9) Chordophonic Organ (chordophonal Organ) modulators, such as pymetrozine or flonicamid.
(10) Mite growth inhibitors, such as clofentezine (cloventezine), hexythiazox (hexythiazox) and flutenzine (diflovidazin) or etoxazole (etoxazole).
(11) Insect gut membrane microbial disruptors, for example Bacillus thuringiensis israelensis, Bacillus sphaericus (Bacillus sphaericus), Bacillus thuringiensis catzeae, Bacillus thuringiensis coulsta subspecies, Bacillus thuringiensis walkman subspecies and b.t. plant proteins: cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1/35Ab 1.
(12) Mitochondrial ATP synthase inhibitors, for example ATP disruptors, such as diafenthiuron (diafenthiuron), or organotin compounds, such as azocyclotin (azocyclotin), cyhexatin (cyclohexadin) and fenbutatin oxide (fenbutatin oxide), or propargite (propagite), or tetradifon (tetradifon).
(13) Uncouplers of oxidative phosphorylation by disruption of proton gradients, such as chlorfenapyr (chlorofenapyr), Dinitrocresol (DNOC), and flubendiamide (sulfluramid).
(14) Nicotinic acetylcholine receptor channel blockers such as bensultap, cartap hydrochloride, thiocyclam and thiosultap-sodium.
(15) Type 0 chitin biosynthesis inhibitors, such as bistrifluron (bistrifluron), chlorfluazuron (chlorefluazuron), difluorourea (diflubenzuron), flucyclourea (flucycloxuron), flufenoxuron (flufenoxuron), hexaflumuron (hexaflumuron), lufenuron (lufenuron), novaluron (novaluron), noviflumron (novaluron), teflubenzuron (teflubenzuron) and triflumuron (triflumuron).
(16) Type 1 chitin biosynthesis inhibitors, such as buprofezin (buprofezin).
(17) Molt disruptors (particularly for Diptera (Diptera), i.e. dipteran-like insects), for example cyromazine (cyromazine).
(18) Ecdysone receptor agonists, such as chromafenozide (chromafenozide), chlorfenozide (halofenozide), methoxyfenozide (methoxyfenozide), and tebufenozide (tebufenozide).
(19) Octopamine receptor agonists, such as amitraz.
(20) Mitochondrial complex III electron transport inhibitors such as hydramethylnone or acequinocyl or fluacrypyrim.
(21) Mitochondrial complex I electron transport inhibitors, for example selected from METI acaricides, such as fenazaquin (fenzaquin), fenpyroximate (fenpyroximate), pyriminofen (pyrimidifen), pyridaben (pyridaben), tebufenpyrad (tebufenpyrad) and tolfenpyrad (tolfenpyrad) or rotenone (Derris).
(22) Voltage-dependent sodium channel blockers, such as indoxacarb (indoxacarb) or metaflumizone (metaflumizone).
(23) Acetyl-coa carboxylase inhibitors, such as tetronic acid and tetramic acid derivatives, for example spirodiclofen (spirodiclofen), spiromesifen (spiromesifen) and spirotetramat (spirotetramat).
(24) Mitochondrial complexes IV electron transport inhibitors, for example phosphines, such as aluminum phosphide, calcium phosphide, phosphines and zinc phosphide, or cyanides, such as calcium cyanide, potassium cyanide and sodium cyanide.
(25) Mitochondrial complex II electron transport inhibitors, such as β -ketonitrile derivatives, for example cyenopyrafen and cyflumetofen, and carboxanilides, for example pyflubiude.
(28) Ryanodine receptor modulators, such as diamides, for example chlorantraniliprole (chlorantraniliprole), cyantraniliprole (cyantraniliprole), and flubendiamide (flubendiamide),
other active compounds, for example, pyriproxyfen (aflodopyropen), alfuramide (afloxolaner), Azadirachtin (Azadirachtin), Benclothiaz, fenpyroximate (Benzoximate), Bifenazate (Bifenazate), flubendiamide (Broflanilide), Bromopropylate (bromopropyralate), mefenamic acid (Chinomethionat), permethrin (chlorpromazine), cyclorambutazine (cromophilate), cyclobromoxyfen (cyclofenamide), cycloxaflufen (cyclofenamid), diclomethazaz, trichlorohydrin (Dicofol), epsilon-methoxybenzylfluthrin (epsilon-fluthrin), epsilon-momethrin, fluquinacrine (flufenamide), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufenacet), flufenacet (flufen), flufenacet), flu, kappa-Bifenthrin (kappa-Bifenthrin), kappa-Tefluthrin (kappa-Tefluthrin), Lotilaner (Lotilaner), Meperfluthrin (Meperfluthrin), meperidine (Paichongding), Pyridalyl (pyridazole), fluquinquine (Pyrifluquinazon), Pyriminostrobin (Pyriminostrobin), spirodiclofen (spirobiclofen), tetradifluthrin (tetramethluthrin), cyantraniliprole (tetraniloprole), Tetrachlorantraniliprole (tetrachlorranilaniliprole), Tioxaloran, Tioxazafen, thiofloxim (thiofluximate), trifluoropyrimidine (pyfluzone) and iodomethane; also bacillus firmus based formulations (I-1582, BioNeem, Votivo), and the following compounds: 1- { 2-fluoro-4-methyl-5- [ (2, 2, 2-trifluoroethyl) sulfinyl ] phenyl } -3- (trifluoromethyl) -1H-1, 2, 4-triazol-5-amine (known from WO 2006/043635) (CAS 885026-50-6), {1 '- [ (2E) -3- (4-chlorophenyl) prop-2-en-1-yl ] -5-fluorospiro [ indol-3, 4' -piperidin ] -1(2H) -yl } (2-chloropyridin-4-yl) methanone (known from WO 2003/106457) (CAS 637360-23-7), 2-chloro-N- [2- {1- [ (2E) -3- (4-chlorophenyl) prop-2-yl-) En-1-yl ] piperidin-4-yl } -4- (trifluoromethyl) phenyl ] isonicotinamide (known from WO 2006/003494) (CAS 872999-66-1), 3- (4-chloro-2, 6-dimethylphenyl) -4-hydroxy-8-methoxy-1, 8-diazaspiro [4.5] dec-3-en-2-one (known from WO 2010052161) (CAS 1225292-17-0), 3- (4-chloro-2, 6-dimethylphenyl) -8-methoxy-2-oxo-1, 8-diazaspiro [4.5] dec-3-en-4-yl carbonate ethyl ester (known from EP 2647626) (CAS 1440516-42-6), 4- (but-2-yn-1-yloxy) -6- (3, 5-dimethylpiperidin-1-yl) -5-fluoropyrimidine (known from WO 2004/099160) (CAS 792914-58-0), PF1364 (known from JP 2010/018586) (CAS 1204776-60-2), N- [ (2E) -1- [ (6-chloropyridin-3-yl) methyl ] pyridin-2 (1H) -ylidene ] -2, 2, 2-trifluoroacetamide (known from WO 2012/029672) (CAS 1363400-41-2), (3E) -3- [1- [ (6-chloro-3-pyridinyl) methyl ] -2-pyridylidene ] -1, 1, 1-trifluoro-propan-2-one (known from WO 2013/144213) (CAS 1461743-15-6), N- [3- (benzylcarbamoyl) -4-chlorophenyl ] -1-methyl-3- (pentafluoroethyl) -4- (trifluoromethyl) -1H-pyrazole-5-carboxamide (known from WO 2010/051926) (CAS 1226889-14-0), 5-bromo-4-chloro-N- [ 4-chloro-2-methyl-6- (methylcarbamoyl) phenyl ] -2- (3-chloro-2-pyridyl) pyrazole-3-carboxamide (known from CN 103232431) (CAS 1449220-44-3), 4- [5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl ] -2-methyl-N- (cis-1-oxo-3-thietanyl) -benzamide, 4- [5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl ] -2-methyl-N- (trans-1-oxo-3-thietanyl) -benzamide and 4- [ (5S) -5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl ] -2-methyl- N- (cis-1-oxo-3-thietanyl) benzamide (known from WO 2013/050317A 1) (CAS 1332628-83-7), N- [ 3-chloro-1- (3-pyridyl) -1H-pyrazol-4-yl ] -N-ethyl-3- [ (3, 3, 3-trifluoropropyl) sulfinyl ] -propionamide, (+) -N- [ 3-chloro-1- (3-pyridyl) -1H-pyrazol-4-yl ] -N-ethyl-3- [ (3, 3, 3-trifluoropropyl) sulfinyl ] -propionamide and (-) -N- [ 3-chloro-1- (3-pyridyl) -1H-pyrazole -4-yl ] -N-ethyl-3- [ (3, 3, 3-trifluoropropyl) sulfinyl ] -propionamide (known from WO 2013/162715 a2, WO 2013/162716 a2, US 2014/0213448 a 1) (CAS 1477923-37-7), 5- [ [ (2E) -3-chloro-2-propen-1-yl ] amino ] -1- [2, 6-dichloro-4- (trifluoromethyl) phenyl ] -4- [ (trifluoromethyl) sulfinyl ] -1H-pyrazole-3-carbonitrile (known from CN 101337937 a) (CAS 1105672-77-2), 3-bromo-N- [ 4-chloro-2-methyl-6- [ (methylamino) thiomethyl ] phenyl ] -1- (1-bromo-N- [ 4-chloro-2-methyl-6- [ (methylamino) thiomethyl ] phenyl ] -1-, (CAS 3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide, (Liudaibenjiaxuanan, known from CN 103109816 a) (CAS 1232543-85-9); n- [ 4-chloro-2- [ [ (1, 1-dimethylethyl) amino ] carbonyl ] -6-methylphenyl ] -1- (3-chloro-2-pyridinyl) -3- (fluoromethoxy) -1H-pyrazole-5-carboxamide (known from WO 2012/034403A 1) (CAS 1268277-22-0), N- [2- (5-amino-1, 3, 4-thiadiazol-2-yl) -4-chloro-6-methylphenyl ] -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide (known from WO 2011/085575A 1) (CAS 1233882-22-8), 4- [3- [2, 6-dichloro-4- [ (3, 3-dichloro-2-propen-1-yl) oxy ] phenoxy ] propoxy ] -2-methoxy-6- (trifluoromethyl) -pyrimidine (known from CN 101337940 a) (CAS 1108184-52-6); (2E) -2- [2- (4-cyanophenyl) -1- [3- (trifluoromethyl) phenyl ] ethylene ] -N- [4- (difluoromethoxy) phenyl ] -hydrazinecarboxamide and 2(Z) -2- [2- (4-cyanophenyl) -1- [3- (trifluoromethyl) phenyl ] ethylene ] -N- [4- (difluoromethoxy) phenyl ] -hydrazinecarboxamide (known from CN 101715774 a) (CAS 1232543-85-9); 3- (2, 2-dichlorovinyl) -2, 2-dimethyl-4- (1H-benzimidazol-2-yl) phenylcyclopropanecarboxylate (known from CN 103524422 a) (CAS 1542271-46-4); (4aS) -7-chloro-2, 5-dihydro-2- [ [ (methoxycarbonyl) [4- [ (trifluoromethyl) thio ] phenyl ] amino ] carbonyl ] -indeno [1, 2-e ] [1, 3, 4] oxadiazine-4 a (3H) -carboxylic acid methyl ester (known from CN 102391261 a) (CAS 1370358-69-2); 6-deoxy-3-O-ethyl-2, 4-di-O-methyl-1- [ N- [4- [1- [4- (1, 1, 2, 2, 2-pentafluoroethoxy) phenyl ] -1H-1, 2, 4-triazol-3-yl ] phenyl ] carbamate ] -alpha-L-mannopyranose (known from US 2014/0275503A 1) (CAS 1181213-14-8); 8- (2-Cyclopropylmethoxy-4-trifluoromethylphenoxy) -3- (6-trifluoromethylpyridazin-3-yl) -3-azabicyclo [3.2.1] octane (CAS 1253850-56-4), (8-trans) -8- (2-cyclopropylmethoxy-4-trifluoromethylphenoxy) -3- (6-trifluoromethylpyridazin-3-yl) -3-azabicyclo [3.2.1] octane (CAS 933798-27-7), (8-cis) -8- (2-cyclopropylmethoxy-4-trifluoromethylphenoxy) -3- (6-trifluoromethylpyridazin-3-yl) -3-azabicyclo [3.2.1] octane (prepared from WO 2007040280A 1, Togazoie, Razoie, Rabap, Rabae, Gauss, Raschizan, 3-4-trifluoromethylphenoxy, 3-yl) -3-azabicyclo [3.2.1] octane (prepared from WO 2007040280A 1, WO 2007040282A 1 knows) (CAS 934001-66-8), N- [ 3-chloro-1- (3-pyridinyl) -1H-pyrazol-4-yl ] -N-ethyl-3- [ (3, 3, 3-trifluoropropyl) thio ] propionamide (known from WO 2015/058021A 1, WO 2015/058028A 1) (CAS 1477919-27-9) and N- [4- (aminothiomethyl) -2-methyl-6- [ (methylamino) carbonyl ] phenyl ] -3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide (known from CN 103265527A) (CAS 1452877-50-7), 5- (1, 3-dioxan-2-yl) -4- [ [4- (trifluoromethyl) phenyl ] methoxy ] -pyrimidine (known from WO 2013/115391A 1) (CAS 1449021-97-9), 3- (4-chloro-2, 6-dimethylphenyl) -4-hydroxy-8-methoxy-1-methyl-1, 8-diazaspiro [4.5] dec-3-en-2-one (known from WO 2010/066780A 1, WO 2011/151146A 1) (CAS 1229023-34-0), 3- (4-chloro-2, 6-dimethylphenyl) -8-methoxy-1-methyl-1, 8-diazaspiro [4.5] decane-2, 4-dione (known from WO 2014/187846A 1) (CAS 1638765-58-8), ethyl 3- (4-chloro-2, 6-dimethylphenyl) -8-methoxy-1-methyl-2-oxo-1, 8-diazaspiro [4.5] dec-3-en-4-ylcarbonate (known from WO 2010/066780A 1, WO 2011151146A 1) (CAS 1229023-00-0), N- [1- [ (6-chloro-3-pyridyl) methyl ] -2(1H) -pyridylidene ] -2, 2, 2-trifluoroacetamide (known from DE 3639877A 1, WO 2012029672A 1) (CAS 1363400-41-2), [ N (E) ] -N- [1- [ (6-chloro-3-pyridyl) methyl ] -2(1H) -pyridylidene ] -2, 2, 2-trifluoroacetamide (known from WO 2016005276A 1) (CAS 1689566-03-7), [ N (Z)) ] -N- [1- [ (6-chloro-3-pyridyl) methyl ] -2(1H) -pyridylidene ] -2, 2, 2-trifluoroacetamide (CAS 1702305-40-5), 3-endo-3- [ 2-propoxy-4- (trifluoromethyl) phenoxy ] -9- [ [5- (trifluoromethyl) -2-pyridyl ] oxy ] -9-azabicyclo [3.3.1] nonane (prepared from WO 2011/105506A 1, Known from WO 2016/133011A 1) (CAS 1332838-17-1).
Examples of safeners which can be admixed with the compounds of the formula (I) and compositions comprising them are, for example, benoxacor (benoxacor), cloquintocet (mexyl)), chloranil (cyclometrinil), cyprosulfamide (cyprosulfamide), dichlormid (dichlormid), fenchlorazole (ethyl)), fenclorim (fenclorim), fluzazole (fluxofenamide), flufenoxaprop (furilazole), isoxadifen (ethyl)), mefenoxan (mefenoyr (diethyl)), naphthalic anhydride (naphthyride), oxaziril (oxabetrinil), 2-methoxy-N- ({4- [ (methylcarbamoyl) amino ] phenyl } sulfonyl) benzamide (CAS 129531-12-0), 4-dichloro-3-5-azaspiro (CAS 3.84-3-5) 2, 2, 5-trimethyl-3- (dichloroacetyl) -1, 3-oxazolidine (CAS 52836-31-4).
Examples of herbicides that can be mixed with the compounds of formula (I) and compositions comprising them are:
acetochlor (acetochlor), acifluorfen (acifluorfen), acifluorfen sodium salt (acifluorfen-sodium), aclonifen (aclonifen), alachlor (alachlor), diachlor (alloidochlor), dichlor (alloxydim), ametryn (ametryn), amicarbazone (amicarbazone), amethol (amirochlorir), amidosulfuron (amisulfuron), 4-amino-3-chloro-6- (4-chloro-2-fluoro-3-methylphenyl) -5-fluoropyridine-2-carboxylic acid, aminocyclopyrachlor (amicarbazolophor), potassium cyclamate (amicarbazone-potassium salt), aminocyclopyrachlor (amicarbazone-potassium), aminocyclopyrachlor (amicarbazone-methyl), pyrimethanate (amicarbazone-methyl), pyrithiobac (amicarbazone), pyrithiobac (amidopyrimethanil (amidopyrin), pyrimethanil (amidopyrimethanil) and pyrimethanil (amidopyrimethanil) salts (amidopyrimethanil) and pyrimethanil (amidopyrimethanil) and pyrimethanil (benbenbenbenbenbenbenbenben-2-p), pyrimethanil (ben-p), pyrimethanil (benbenbenbenbenbenbenben-pyrimethanil (ben-p), pyrimethanil (benbenben-pyrimethanil-p) salts (benbenben-p-pyrin, pyrimethanil-p) and pyrimethanil-pyrin, pyrimethanil-p-pyrin, pyrimethanil-p-pyrin, pyribenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenben-ben-benbenbenbenbenbenbenbenben-benbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenbenben, Azafenidin, azimsulfuron, beflubutamid (beflubutamid), benfurazolin (bensulodin), benfurazolin (bensulin), bensulam-ethyl (bensulin-ethyl), benfluralin (benfluralin), benfuresate (benfuresate), bensulfuron (bensuluron), bensulfuron methyl (bensuluron-methyl), bensulide (bensulide), bentazone (bentazone), benzobicolon (benzobicyclon), benzofenap (benzofenap), fluroxypyr (bicyclopyron), bifenox (bifenox), bialaphos (bisphenox), bialaphos (bisphenoxide), bialaphos (bispyribac-sodium), bisbentazon (bromoxynil), bromoxynil (bromoxynil-ethyl), bromoxynil (bromoxynil-N-methyl), bromoxynil (bromoxynil), bromoxynil (bromoxynil-n (bromoxynil), bromoxynil-n-methyl, bromoxynil (bromoxynil), bromoxynil-methyl-ethyl (bromoxynil), bromoxynil (bromoxynil-methyl, bromoxynil), bromoxynil-methyl, bromoxynil (bromoxynil), bromoxynil-methyl, bromoxynil, and a salt of a, Butachlor (butachlor), butafenacil (butafenacil), butafosinate (butamifos), butachlor (buterachlor), butralin (butralin), butafenacet (butroxydim), butamolide (buthylate), cafenstrole (cafenstrole), acetochlor (carbetamide), carfentrazone (carfentrazone), carfentrazone-ethyl (carfentrazone-ethyl), chlorambucil (chlorfenvinphos), chlorsulfuron (chlorobromoron), chlorambucil (chlorfenamic), varfen (chlorfenamic-sodium), avenyl (chlorfenapyr-sodium), clofentrazone (chlorfenapyr-ethyl), chlorfluoren (chlorflufen), chlorfluron (chlorfluron-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorsulfuron (chlorsulfuron), chlorfenapyr (chlorsulfuron (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr-methyl (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlorfenapyr-methyl), chlorfenapyr (chlor, Clethodim (clindamm), clodinafop (clodinafop), clodinafop-propargyl (clodinafop-propargyl), clomazone (clomazone), clomeprop (clomeprop), clopyralid (clopyrloid), cloransulam (cloramam-methyl), cumyluron (cumyluron), cyanamide (cyclamide), cyanazine (cyramazine), cyhalofop (cycloate), cyclopremate, cyclosulfamuron (cyclosulfamuron), cyclosulfuron (cyclooxdim), cyclohalofop (cyhalofop), cyhalofop-butyl), cyhalofop (cyramon-butyl), 2, 4-D-butoxyethyl ester (2, 4-tyrafop), 2, 4-butylbutoxyethyl ester (2, 4-tyr-butyl-4-2, 4-dimethylolamin (2, 4-dimethylolam), 2, 4-dimethylbuthanol (2, 4-dimethylxanthil-4-2, 4-dimethylxanthiom-2, 4-butyl-2, 4-dimethylxanthil (cyclomedoxolamine), 2, 4-dimethylxanthil (cyclomedoxolate, 2, 4-dimethylxanthil (cyclomedoxolate, 4, 2, 4, dimethylxanthate), and dimethylxanthil (2, 4-2, dimethylxanthil, 2, 4, 2, 4-methyl-2, 4, 2, 4-2, dimethylxanthil, 2, 4, dimethylxanthil, 2, dimethylxanthil, 4, dimethylxanthil, 2, 4, dimethylxanthil, and a, dimethylxanthil, 2, dimethylxanthil, 2, dimethylxanthil, and a, 2, 4-D-ethyl ester (2, 4-D-ethyl), 2, 4-D-2-ethylhexyl ester (2, 4-D-2-ethylhexyl), 2, 4-D-isobutyl ester, 2, 4-D-isooctyl ester, 2, 4-D-isopropylammonium salt, 2, 4-D-potassium salt, 2, 4-D-triisopropanolammonium salt and 2, 4-D-triethanolamine (2, 4-D-tromine), 2, 4-DB-butyl ester, 2, 4-DB-dimethylammonium salt, 2, 4-DB-isooctyl ester, 2, 4-DB-potassium salt and 2, 4-DB-sodium salt, diuron (dymron), dalapon (dalapon), Dazomet, decanol, betaine (desmedipham), desosyl-pyrazolate (DTP), dicamba (dicamba), dichlobenil (dichlobenil), 2- (2, 4-dichlorobenzyl) -4, 4-dimethyl-1, 2-oxazolidin-3-one, 2- (2, 5-dichlorobenzyl) -4, 4-dimethyl-1, 2-oxazolidin-3-one, 2, 4-dichloropropionic acid (dichlorprop), 2, 4-dichloropropionic acid (dichlorprop-P), dichloroxypropionic acid (dichlorofop), diclofop-methyl, diclofop-P-methyl, diclosulam (diclosulam), difloram (difenoconazole), flufenacet (difenon), diflufenuron (diflufenuron), diflufenflurron (diflubenzuron), diflufenflururon sodium salt (diflufenuron), diflufenuron (diflufenuron-sodium salt (diflufenuron), diflufenflurron (diflubenzuron), and sodium salt (diflufenflurron) in (diflufenflurron), and the like, Dimercaptote (dimepiperate), dimethenamid (dimethachlor), isoethazine (dimethacryn), dimethenamid (dimethenamid-P), dimethenamid-P, dimetrasulfuron, dinitramine (dinitramine), dinotefuran (dinoterb), diphenoxamine (diphenamid), diquat (diquat), diquat-dibromide (diquat-dibromide), dithiopyr (dithiopyr), diuron (diuron), DNOC, endothal (othial), EPTC, penoxsulam (propcarb), ethalfluorine (ethofluran), ethametsulfuron (ethofen-methyl), ethoxyfen (ethoxyfen-4-ethoxyfen), ethoxyfen-ethyl-3- (ethoxyfen-4-ethoxyfen), ethoxyfen-3-ethoxyfen-ethyl-5- (ethoxyfen-ethyl-3-ethoxyfen-ethyl), ethoxyfen-4-ethoxyfen (ethoxyfen-ethyl-3-ethoxyfen-methyl), 5-dihydro-1H-tetrazol-1-yl ] phenyl } ethanesulfonamide), F-7967 (i.e., 3- [ 7-chloro-5-fluoro-2- (trifluoromethyl) -1H-benzimidazol-4-yl ] -1-methyl-6- (trifluoromethyl) pyrimidine-2, 4(1H, 3H) -dione), fenoxaprop (fenoxaprop-P), fenoxaprop-ethyl (fenoxaprop-ethyl), fenoxaprop-ethyl (fenoxaprop-P-ethyl), fenoxaprop-ethyl (fenoxaprop), fenoquine, fenquinotrione, fentrazamide (fentrazamide), lolium fluoride (fiamiprop), lolium fluoride-isopropyl (flamprop-M-isoproyl), flamprop methyl ester (flamprop-M-methyl), mefenoxaprop-M-methyl, Flazasulfuron (fluzasulfuron), florasulam (florasulam), fluazifop-butyl (fluazifop-P-butyl), fluazifop-butyl (fluazifop-P-butyl), fluazifop-methyl (flucarbazone), fluazifop-sodium (flucarbazone-sodium), fluazifop (fluazuron), flufluralin (flufluralin), flufenacet (flufenacet), flupyridazinyl (flufenapyr), flupyridazinyl (flufenacet), flufenacet (flufenacet-butyl), flufenacet (flufenacet), fluorobenfluridone (fluoroben-ethyl), fluorobenfluridone (fluridone), flumetol (fluridone), flumetol (flurfenacet (fluridone), flurfenate (flurfenacet (flurfenac), flurfenac (flurfenacet (flurfenac), flurfenacet (flurfenac), flurfenac (flurfenac, flurfenacet (flurfenac), flurfenac, flurfenacet (flurfenac, flurfenacet (flurfenac, flurfenacet (flurfenac, flurfenacet (flurfenac), flurfenac, flurfenacet (flurfenac ), flurfenacet (flurfenac, flurfenacet (flurfenac, flurfenacet (flurfenac, flurfenacet (flurfenac, flurfenacet (flurfenac, flurfenacet (flurfenacet, flurfenac, flurfenacet (flurfenac, flurfenac), flurfenacet (flurfenac), flurfenacet, flurfenac), flurfenacet (flurfenac, flurfena, Tetrafluoropropionic acid (flupropanate), flazasulfuron (flupyrsulfuron), flazasulfuron-methyl-sodium salt (flupyrsulfuron-methyl-sodium), fluazinone (fluidurone), flutolone (fluuroxime), fluroxypyr (fluoxypyr), fluroxypyr (fluxadim), fluazifop (fluazinam), fluazifop-methyl (fluthiamide), fomesafen (fomesafen), fomesafen sodium salt (fomesafen-sodium), fomesafen (fomesafen), glufosinate (glufosinate), glufosinate-ammonium salt (glufosinate-ammonium salt), glufosinate-ammonium salt (glufosinate), glufosinate-ammonium salt (glufosinate-ammonium salt), glufosinate-ammonium salt (ammonium-ammonium salt), glufosinate-ammonium salt (ammonium salt), glufosinate-ammonium salt, ammonium salt (ammonium salt, ammonium salt, Glyphosate diammonium salt (glyphosate-dimonium), glyphosate dimethylammonium salt (glyphosate-dimonium), glyphosate potassium salt (glyphosate-potassium), glyphosate sodium salt (glyphosate-sodium), and glyphosate trimethylsulfonium salt (glyphosate-trimetonium), H-9201 (i.e., O- (2, 4-dimethyl-6-nitrophenyl) O-ethyl isopropyl thiophosphoramide ester (O- (2, 4-dimethyl-6-nitrophenyl) O-ethyl isopropyl thiophosphoramide), fluorochloropyrimidinate (halauxifen), fluorochloropyrimidine (halauxifen-methyl), fluorohalosulfuron methyl ester (halauxifen-methyl), fluorohalosulfuron-ethyl ester (halauxifen-ethyl ester), pyrazosulfuron-ethyl ester (halafenethyl ester), pyrazosulfuron-methyl ester (halafen-ethyl ester), pyrazosulfuron-ethyl ester (fluoroglycofen-ethyl ester (P-ethyl ester), pyrazoxyfen-ethyl ester (P-ethyl ester), and (pyrazoxyfen-ethyl ester (P-ethyl ester), Methyl fluazifop-methyl (haloxyfop-methyl), methyl fluazifop-P-methyl, hexazinone (hexazinone), HW-02 (i.e., 1- (dimethoxyphosphoryl) ethyl- (2, 4-dichlorophenoxy) acetate), imazamethabenz (imazamethabenz z), methyl imazamethabenz (imazamethabenz-methyl), imazapic (imazamox), imazapic ammonium (imazamox-ammonium), imazapic (imazapic-ammonium), imazapic (imazapyr), imazapic isopropyl ammonium (imazapyr-isopyrammonionium), imazaquin (imazaquin), imazaquin ammonium (imazaquin-ammonium), imazaquin (imazapic-imazapine), imazaquin (imazapine), imazapine ammonium (imazamox-ammonium), imazamox-isoprozamox-imazosulfuron (imazosulfuron), imazosulfuron-iodosulfuron (imazosulfuron), imazosulfuron-methyl-iodonium (imazosulfuron), imazosulfuron (imazosulfuron-methyl-iodonium), imazosulfuron (imazosulfuron-methyl-ethyl), imazosulfuron (imazosulfuron-methyl-ethyl-methyl-iodonium), imazosulfuron (imazosulfuron-methyl-ethyl) and imazachlor (imazosulfuron) are included in, Iodosulfuron-methyl-sodium, ioxynil (ioxynil-methyl-sodium), ioxynil (ioxynil), octanoylisobenzonitrile (ioxynil-octanoate), ioxynil-potassium and ioxynil-sodium, triazolam (ipfencarbazone), isoproturon (isoproturon), isooxauron (isouron), isoxaben (isoxaben), isoxaflutole (isoxaflutole), terbinam (karbutilate), KUH-043 (i.e. 3- ({ [5- (difluoromethyl) -1-methyl-3- (trifluoromethyl) -1H-pyrazol-4-yl ] methyl } sulfonyl) -5, 5-dimethyl-4, 5-dihydro-1, 2-oxazole), ketospiradox, lactofen-ethyl, cyclobutyluron (MCtoluron), butoxynil (MCbutoxynil-PA (MCbutoxynil), metosulbuthyl-PA (MCbutoxynil-PA), and their salts, MCPA-dimethylammonium salt, MCPA-2-ethylhexyl salt, MCPA-isopropylammonium salt, MCPA-potassium salt and MCPA-sodium salt, MCPB-methyl ester, MCPB-ethyl ester and MCPB-sodium salt, 2-methyl-4-chloropropionic acid (mecoprop), sodium 2-methyl-4-chloropropionate (mecoprop-sodium) and butoxyethyl 2-methyl-4-chloropropionate (mecoprop-butyl), 2-methyl-4-chloropropionic acid (mecoprop-P), butoxyethyl 2-methyl-4-chloropropionate (mecoprop-P-butyl), dimethylammonium salt of 2-methyl-4-chloropropionic acid (mecoprop-P-dimethylammonium), 2-ethylhexyl-2-methyl-4-chloropropionate (mecoprop-2-ethylhexyl) and 2-methyl-2-chloropropionate 4-chloropropionate potassium salt (mecoprop-P-potassium), mefenacet (mefenacet), mefenacet (meflulidide), mesosulfuron (mesosulfuron), mesosulfuron-methyl (mesosulfuron-methyl), mesotrione (mesotrione), methabenzthiazuron (methabenzthiazuron), metam (metam), metamifop (metamifop), metamitron (metamitron), pyrazosulfuron (metachlor), metazosulfuron (metazosulfuron), methabenzthiazuron (methabenzthiazuron), methidathion (metazosulfuron), methidathion (methazosulfuron), methidaron (methazosulfuron), methidathion (metosulron), methidaron (metosul), metosulron (metosulron), metosulron (metosulron) methyl-methyl, metosulron (metosulron) or (metosulron), metosulron (metosulron) salt, metosulron (metosulron) and metosulron (metosulron) salt, metosulron (metosulron), metosulron (metosulron) or (metosulron), metosulron (metosulron), metosulron) or (metosulron), metosulron (metosulron) methyl-methyl, metosulron (metosulron), metosulron) or (metosulron) or (metosulron), metosulron (metosulron) and metosulron (metosulron) or (metosulron), metosulron (metosulron), metosulron) of (metosulron), metosulron (metosulron) of (metosulron), metosulron (metosulron), metosulron (metosulron), metosulron (metosulron), metosulron) of (metosulron), metosulron (methyl-methyl, metosulron (methyl-methyl Methylpentanamide), NGGC-011, napropamide (napropamide), NC-310 (i.e. [ 5-benzyloxy-1-methyl-1H-pyrazol-4-yl ] (2, 4-dichlorophenyl) methanone), nicosulfuron (neburon), nicosulfuron (nicosulfuron), nonanoic acid (pelargonic acid), norflurazon (norflurazon), oleic acid (fatty acid), prosulfocarb (orbencarb), orthosulfamuron (orthiosulfuron), oryzalin (oryzalin), oxadiargyl (oxaadryl), oxadiazon (oxadazon), sulfosulfuron (oxasulfuron), oxaziclomefone (oxaziclomefon), oxyfluorfen (oxaflufen), paraquat (oxaquat), diclofop (paraquat), penoxsulam (penoxsulam), penoxsulam (penoxsulam), penoxsulam (penoxsulam), penoxsulam, Bensulfuron-methyl (phenmedipham), picloram (picloram), flupyrazoxamine (picolinafen), pinoxaden (pinoxaden), piperaphos (piprophos), pretilachlor (pretilachlor), primisulfuron (primisulfuron), primisulfuron (methyl-methyl), prodiamine (prodiamine), clethodim (profenodim), prometryn (prometon), prometryn (prometryn), propyzamide (propachlor), propanil (propanil), bensulfuron-methyl (propaquizafop), promazine (propazone), propyzamide (propazone), propafenone (propaferon), propaferon (propaferon), pyrazosulfuron-ethyl (propaferon), pyrazosulfuron (pyrazosulfuron-ethyl), pyrazosulfuron (pyrazosulfuron), pyrazosulfuron (pyrazosulfuron-ethyl), pyrazosulfuron (pyrazosulfuron-ethyl, pyrazosulfuron), pyrazosulfuron-ethyl, pyrazosulfuron (pyrazosulfuron-methyl), pyrazosulfuron-ethyl, pyrazosulfuron-methyl), pyrazosulfuron (pyrazosulfuron-methyl), pyrazosulfuron-methyl, pyrazosulfuron-ethyl, pyrazosulfuron-methyl, pyrazosulfuron-ethyl, pyrazosulfuron-methyl, pyrazosulfuron-ethyl, pyrazosulfuron-methyl, pyrazosulfuron-ethyl, pyrazosulfuron-p-ethyl, pyrazosulfuron-p-ethyl, pyrazosulfuron-p-methyl, pyrazosulfuron-p-ethyl, pyrazosulfuron-p-ethyl, pyrazosulfuron-methyl, pyrazosulfuron-ethyl, pyrazosulfuron-methyl, pyrazosulfuron-p-methyl, pyrazosulfuron-p-ethyl, pyrazosulfuron-methyl, pyrazosulfuron-p-ethyl, pyrazosulfuron-methyl, pyrazosulfuron-p-ethyl, pyrazosulfuron-, Benconazole (pyrazoxyfen), pyribambernz, pyribenzoxim (pyribamberz-isoproyl), pyribenzoxim (pyribamberz-propyl), pyribenzoxim (pyribenzoxim), pyribenzoxim (pyributicarb), pyributicarb (pyridazole), pyridate (pyriftalid), pyribenzoxim (pyriftalid), pyriminobac (pyriminobac-methyl), pyriminobac (pyrithiobac), pyrithiobac (pyrithiobac-sodium), pyroxaflufen (pyroxapyroxasulfone), pyroxsulam (pyroquinuron-ethyl), quinacr (quinacr), quinoxyfen (quinophthalone), quizalofop (P-ethyl), pyribenzoethyl-ethyl (pyribenzoethyl-ethyl), pyribenzofenacetone (P-ethyl), pyribenzofenacetone (pyribenzofenacetone), pyribenzofenacetone (pyribenzofenapyr-ethyl), pyribenzofenacetone (pyribenzofenap), pyribenzofenacetone (pyribenzofenacetone-ethyl, pyribenzofenap-ethyl, pyribenzofenacetone (pyribenzofenap-ethyl, pyribenzofenacetone (pyribenzofenacetone-ethyl, pyribenzofenap-ethyl, pyribenzofenacetone-ethyl, pyribenzofenacetone (pyribenzofenacet-ethyl, pyribenzofenacetone (pyribenzofenacetone, pyribenzofenap-ethyl, pyribenzofenacetone (pyribenzofenacetone, pyribenzofenacetone (pyribenzofenacetone, pyribenzofenacetone (pyribenzofenacetone, pyribenzofenacetone (pyribenzofenacet, pyribenzofenacetone, pyribenazoles (pyribenazoles, pyribenzofenacetone (pyribenzofenacetone, pyribenzofenacetone (pyribenzofenacetone, pyribenzofenacet (pyribenzofenacetone, pyribenazoles, pyribenzofenacetone, pyribenazoles, pyribenzo, Simetryn (simetryn), SL-261, sulcotrione (sulcotrion), sulfentrazone (sulfometrizone), sulfometuron (sulfometuron), sulfometuron methyl ester (sulfometuron-methyl), sulfometuron (sulfofurouron), SYN-523, SYP-249 (i.e. 1-ethoxy-3-methyl-1-oxobut-3-en-2-yl 5- [ 2-chloro-4- (trifluoromethyl) phenoxy ] -2-nitrobenzoate), SYP-300 (i.e. 1- [ 7-fluoro-3-oxo-4- (prop-2-yn-1-yl) -3, 4-dihydro-2H-1, 4-benzoxazin-6-yl ] -3-propyl-2-thioxoimidazolidine-4, 5-dione), 2, 3, 6-TBA, TCA (trichloroacetic acid), TCA-sodium, buthiuron (tebuthiuron), benzofuranone (tefuryltrione), tembotrione (tembotrione), tepraloxydim (tepraloxydim), terfenadine (terbacil), terbufos (terbutarb), terbutyron (terbuteton), terbutylazine (terbutryzin), terbutryn (terbutryyn), dimethenamid (theylchloride), thiazopyr (thiazopyr), thiencarbazone (thiencarbazone), thiencarbazone-methyl, thifensulfuron (thiencarbazone-methyl), thifensulfuron (thiencuron), thifensulfuron-methyl, thiofensulfuron (thifenuron-methyl), thiobensultone (thifenuron-methyl), thifenfluridone (thifenfluridone), teflufen (thifenuron-methyl), thifensulfuron-methyl, thifenfluridone (thifensulfuron-methyl), thifenfluridone (thifenuron (thifenfluridone), thifensulfuron-methyl), thifenfluridone (thifenfluridone), thifenuron (thifenuron-methyl), thifenfluridone (thifenfluridone), thifenfluridone (thifenfluridone), thifenfluridone (thifenfluridone), thifenfluridone (thifenfluridone), thifenfluridone (thifenfluridone), thifenfluridone (thifenfluridone), thifenfluridone (thifenfluridone) and thifenfluridone (thifenfluridone) methyl), thifenfluridone (thifenfluridone), thifenfluridone (thifenfluridone) methyl), thifenflurfenfluridone), thifenfluridone) methyl), thifenfluridone (thifenfluridone), thifenfluridone) or thifenfluridone (thifenflurfenfluridone (thifenfluridone), thifenfluridone (thifenfluridone), thifenflur, Trifloxysulfuron (trifloxysulfuron), trifloxysulfuron sodium salt (trifloxysulfuron-sodium), triflumimoxazin, trifluralin (trifluralin), triflusulfuron (triflusulfuron), triflusulfuron methyl ester (triflusulfuron-methyl), triflusulfuron (tritosulfuron), urea sulfate, dichlormate (vernolate), XDE-848, ZJ-0862 (i.e., 3, 4-dichloro-N- {2- [ (4, 6-dimethoxypyrimidin-2-yl) oxy ] benzyl } aniline), and the following compounds:
Examples of plant growth regulators are:
activated esters (acetenzalar), acibenzolar-S-methyl, 5-aminolevulinic acid, pyrimidinol (ancymidol), 6-benzylaminopurine, brassinolide (Brassicanolid), catechol (catechol), chlormequat chloride (chlormequat chloride), clomeprop (cyclopropp), cyclamic acid (cyclanilide), 3- (cyclopropyl-1-enyl) propionic acid, daminozide (daminozide), dazomet, decanol, difuranic acid (dikegulac), difuranic acid sodium (dikegulac-sodium), endotherm (othal), endothermium (endothermium), endothermium (indoxyl-sodium) and endothermium mono (N, N-dimethylalkylammonium), ethephen (ethephon), flumetralin (flumicloramide), fluorenol (3-xanthenol), flubenzuron (indole-3-acetate), benzuron (indole-chloride (indole-3), benzuron (indole-chloride), benzpyrolide (indole-chloride), xanthene-chloride (indole-chloride), indole-chloride (indole-chloride), pyridine-chloride (indole-chloride) and (indole-chloride) or aldehyde, pyridine-chloride) or aldehyde, 4-indol-3-yl-butyric acid, isoprothiolane (isoprothiolane), probenazole (probenazole), jasmonic acid (jasmonic acid), maleic hydrazide, mepiquat chloride (mepiquat chloride), 1-methylcyclopropene, methyl jasmonate, 2- (1-naphthyl) acetamide, 1-naphthylacetic acid, 2-naphthyloxyacetic acid, a nitrophenolate mixture (nitrophenolate-mixture), paclobutrazol (paclobutrazol), N- (2-phenylethyl) -beta-aminopropionic acid, N-phenylo-carbamoylbenzoic acid (N-phenylthioacetamic acid), prohexadione acid (prohexadione), calcium prohexadione-calcium, jasmone (hydroxyjamesotrione), salicylic acid, strigolactone (strigolactone), tetrachloronitrobenzene (tetrachlorzene), thidiazuron (thidiazuron), triacontanol (triacontanol), trinexanol (trinexapac-ethyl-propionate), N-phenylo-carbamoylbenzoic acid (N-phenylthiocarbamic acid (N-phenyl-ethyl-benzoate), propine (propine), thidiazuron (trithiolane), thidiazuron-methyl-ethyl-4-ethyl-4-ethyl-4-ethyl-phenyl-ethyl-4-phenyl-ethyl-phenyl-ethyl-4-phenyl-ethyl-phenyl-4-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-ethyl-phenyl-, tstedof, uniconazole (uniconazole), uniconazole-P.
Method and use
The compounds of formula (I) and compositions comprising them have potent microbicidal activity and/or plant defense modulating potential. They are useful for controlling unwanted microorganisms, such as unwanted fungi and bacteria. They can be used in particular for crop protection (they control microorganisms which cause plant diseases) or for the protection of materials which are described in more detail below (e.g. industrial materials, wood, storage goods). More specifically, the compounds of formula (I) and compositions comprising the same are useful for protecting seeds, germinating seeds, emerging seedlings, plants, plant parts, fruits, harvests and/or the soil in which the plants are grown from unwanted microorganisms.
As used herein, control ("control" or "controlling") includes protective treatment, therapeutic treatment, and eradication treatment of unwanted microorganisms. The unwanted microorganism may be a pathogenic bacterium, a pathogenic virus, a pathogenic oomycete or a pathogenic fungus, more particularly a phytopathogenic bacterium, a phytopathogenic virus, a phytopathogenic oomycete or a phytopathogenic fungus. As described in detail below, these phytopathogenic microorganisms are causative agents (cause agents) of a broad spectrum of plant diseases.
More specifically, the compounds of formula (I) and compositions containing them are useful as fungicides. For the purposes of the present invention, the term "fungicide" means a compound or composition which can be used in crop protection to control unwanted fungi, such as Plasmodiophoromycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes and Deuteromycetes, and/or to control oomycetes.
The compounds of formula (I) and compositions containing them are also useful as antibacterial agents. In particular, they can be used in crop protection, for example to combat undesirable bacteria, such as the Pseudomonadaceae (pseudomonas adaceae), Rhizobiaceae (Rhizobiaceae), xanthomonas (Xanthomonadaceae), Enterobacteriaceae (Enterobacteriaceae), Corynebacteriaceae (Corynebacteriaceae) and Streptomycetaceae (Streptomycetaceae).
The compounds of formula (I) and compositions comprising them are also useful as antiviral agents in crop protection. For example, the compound of formula (I) and the composition comprising the same may have an effect on diseases caused by plant viruses such as Tobacco Mosaic Virus (TMV), tobacco rattle virus (tobaco rate virus), tobacco stunt virus (tstuyv), tobacco leaf curl virus (VLCV), tobacco green leaf mosaic virus (tbbac nevira mosaic virus) (TVBMV), tobacco necrotic stunt virus (tbbacco necrotic dwarfvira virus) (tntncv), tobacco stripe virus (tobaco strain virus) (TSV), potato virus x (pvx), potato virus Y, S, M and a, potato virus (potaco mosaic virus) (PAMV), potato virus (patoto virus) (PMTV), potato virus (patoto-virus) (PMTV), and potato virus (patoto virus) (PMTV), Alfalfa Mosaic Virus (AMV), Cucumber Mosaic Virus (CMV), cucumber green mosaic virus (CGMMV), cucumber yellows virus (CuYV), Watermelon Mosaic Virus (WMV), tomato spotted virus (TSWV), tomato ringspot virus (TomRSV), sugarcane mosaic virus (SCMV), rice dwarf virus (rice dwarf virus), rice stripe virus (virus), rice black-streaked dwarf virus (strawberry virus), strawberry streak virus (strawberry virus) (SMBV), strawberry streak virus (strawberry virus), strawberry shrunken-streaked virus (SMBV), strawberry virus (strawberry virus), strawberry yellow virus (CGV), cucumber yellow spot virus (CGMV), cucumber yellow spot virus (CGV), cucumber yellow spot virus (SCV), cucumber black-streaked strawberry virus (SVBV), cucumber yellow spot virus (SCV), and strawberry virus (SCV) Broad Bean Wilting Virus (BBWV) and Melon Necrotic Spot Virus (MNSV).
The invention also relates to a method for controlling phytopathogenic fungi, preferably selected from the genera puccinia, such as puccinia recondita, puccinia graminis or puccinia tritici; single spore rust species, such as, for example, single spore rust of verrucosa; and rust pathogens, in particular selected from the genera phakopsora, such as, for example, phakopsora fusca; camelina rust species, such as camelina coffea, and phakopsora species, such as phakopsora pachyrhizi or phaeophyma pomonensis, comprising the step of applying at least one compound of formula (I) or at least one composition of the invention to the microorganism and/or its habitat (to the plant, plant part, seed, fruit or soil in which the plant is growing).
Generally, when the compounds of formula (I) and compositions comprising them are used in therapeutic or protective methods for the control of phytopathogenic fungi, they are applied to the plants, to parts of plants, to fruits, to seeds or to the soil or substrate in which the plants are growing, in an effective and plant-compatible amount. Suitable substrates which can be used for growing plants include inorganic-based substrates, such as mineral wool (in particular asbestos), perlite, sandy soil or gravel; organic substrates such as peat, pine bark or sawdust; and petroleum-based substrates such as polymer foams or plastic beads. Effective and plant compatible amountMeans an amount sufficient to control or destroy those present or liable to appear on the fieldFungi, and does not cause any significant phytotoxic symptoms to the crop. The amounts may vary within wide limits depending on the fungus to be controlled, the type of crop, the stage of crop growth, the climatic conditions and the various compounds or compositions of formula (I) used. This amount can be determined by systematic field trials within the capabilities of those skilled in the art.
Plants and plant parts
The compounds of formula (I) and compositions comprising the same may be applied to any plant or plant part.
Plant and method for producing the sameAll plants and plant populations are meant, for example, desired and undesired wild plants or crop plants (including naturally occurring crop plants). Crop plants may be plants which are obtainable by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or a combination of these methods, including genetically modified plants (GMOs or transgenic plants) and plant cultivars which may or may not be protected by plant breeders' rights.
Genetically modified plants (GMO)
Genetically modified plants (GMO or transgenic plants) are plants in which a heterologous gene has been stably integrated into the genome. The term "heterologous gene" essentially means a gene that is provided or assembled in vitro in a plant and which, when introduced into the nuclear, chloroplast or mitochondrial genome, confers new or improved agronomic or other characteristics to the transformed plant either by expression of a protein or polypeptide of interest or by downregulation or silencing (using for example antisense, cosuppression, RNA interference-RNAi-or microRNA-miRMA-techniques) of one or more other genes present in the plant. Heterologous genes located in the genome are also referred to as transgenes. A transgene defined by its specific location in the plant genome is called a transformation or transgenic line (transgenic event).
Plant cultivarsIt is understood to mean plants which have novel properties ("traits") and which have been obtained by conventional breeding, mutagenesis or recombinant DNA techniques. They may be cultivarsA variety, a biological type, or a genotype.
Plant partsIt is to be understood as meaning all parts and organs of plants above and below the ground, such as shoots, leaves, needles, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes. Plant parts also include harvested material as well as vegetative and generative propagation material, for example cuttings, tubers, rhizomes, ramets and seeds.
Plants that can be treated according to the methods described herein include the following: cotton, flax, grapevine, fruit, vegetables, such as rosaceous species (Rosaceae sp.) (e.g. pome fruit species, such as apples and pears, and stone fruit species, such as apricots, cherries, almonds and peaches, and seedless small fruit species, such as strawberries), ribeoieae species, Juglandaceae species (juglaceae sp.), Betulaceae species (Betulaceae sp.), Anacardiaceae species (Anacardiaceae sp.), Fagaceae species (Fagaceae sp.), Moraceae species (Moraceae sp.), fagacaenaceae species, Oleaceae species (Oleaceae sp.), Lauraceae species (Musaceae sp.), macaque species (actinidiaceae sp.), rosaceous species (Rosaceae sp.), rubus species), rosaceous species (Rosaceae sp.), rubus species (Rubiaceae), Rubiaceae species (rosaceous species), Rubiaceae (rosaceous species (rosaceous sp.), Rubiaceae (rosaceous species (rosaceous sp.), rosaceous species (Rubiaceae), Rubiaceae (rosaceous species (Rubiaceae), Rubiaceae (Rubiaceae), Rubiaceae (rosaceous species (such as well as a spp.), rosaceous species (such as a, Orange and grapefruit); solanaceae (Solanaceae sp.) (e.g., tomato), Liliaceae (Liliaceae sp.), Asteraceae (Asteraceae sp.) (e.g., lettuce), Umbelliferae (Umbelliferae sp.), Cruciferae (Cruciferae sp.), Chenopodiaceae (Chenopodiaceae sp.), Cucurbitaceae (Cucurbitaceae sp.) (e.g., cucumber), Alliaceae (Alliaceae sp.) (e.g., leek, onion), and Papilionaceae (Papilionaceae sp.) (e.g., pea); major crop plants, such as graminaceous species (Gramineae sp.) (e.g., corn, turf grass (turf), cereals (e.g., wheat, rye, rice, barley, oats, millet, and triticale)), compositae species (e.g., sunflower), cruciferous species (e.g., white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts (Brussels sprouts), pakchoi, kohlrabi, radish, and canola, mustard, horseradish, and cress), fabaceae species (fabaceae sp.) (e.g., beans, peanuts), sphenoidaceae species (e.g., soybeans), solanaceae species (e.g., potatoes), chenopodiaceae species (e.g., sugar beet, fodder beet, swiss beet, beetroot); useful plants and ornamentals in horticulture and forests; and genetically modified varieties of each of these plants.
Plants and plant cultivars that can be treated by the methods disclosed above include plants and plant cultivars that are resistant to one or more biotic stresses, i.e., plants that have improved defense against animal or microbial pests, e.g., against nematodes, insects, mites, phytopathogenic fungi, bacteria, viruses and/or viroids.
Plants and plant cultivars that can be treated by the methods disclosed above include those plants that are resistant to one or more abiotic stresses. Abiotic stress conditions can include, for example, drought, low temperature exposure, heat exposure, osmotic stress, water logging, increased soil salinity, enhanced mineral exposure, ozone exposure, intense light exposure, limited nitrogen nutrient utilization, limited phosphorus nutrient utilization, shade avoidance.
Plants and plant cultivars that can be treated by the methods disclosed above include those plants characterized by improved yield characteristics. The increased yield in the plants may be attributed to: for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen utilization, enhanced carbon assimilation, improved photosynthesis, increased germination and accelerated maturation. Yield may also be affected (under stress and non-stress conditions) by improved plant architecture (plant architecture) including, but not limited to, early flowering, flowering control for hybrid seed production, seedling vigor, plant size, internode number and internode spacing, root growth, seed size, fruit size, pod or ear number, seed number per pod or ear, seed quality, increased seed plumpness, reduced seed dispersal, reduced pod dehiscence, and lodging resistance. Other yield traits include seed composition, such as carbohydrate content and composition, e.g. cotton or starch, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
Plants and plant cultivars that can be treated by the methods disclosed above include plants and plant cultivars that are hybrid plants that have expressed a hybrid vigor or hybrid vigor characteristic that generally results in higher yield, vigor, health, and resistance to biotic and abiotic stresses.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) that can be treated by the methods disclosed above include plants and plant cultivars that are herbicide tolerant plants, i.e., plants that are tolerant to one or more given herbicides. Such plants may be obtained by genetic transformation or by selection of plants comprising a mutation conferring tolerance to such herbicides.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) that can be treated by the methods disclosed above include plants and plant cultivars that are insect-resistant transgenic plants, i.e., plants that are resistant to attack by certain target insects. Such plants may be obtained by genetic transformation or by selection of plants comprising mutations conferring such insect resistance.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) that can be treated by the methods disclosed above include plants and plant cultivars that are disease-resistant transgenic plants, i.e., plants that are resistant to attack by certain target insects. Such plants may be obtained by genetic transformation or by selection of plants comprising mutations conferring such insect resistance.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) that can be treated by the methods disclosed above include plants and plant cultivars that are tolerant to abiotic stress. Such plants may be obtained by genetic transformation or by selecting for plants comprising a mutation conferring such stress resistance.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) that can be treated by the above-disclosed methods include plants or plant cultivars that exhibit altered quantity, quality, and/or storage stability of the harvested product, and/or altered characteristics of particular ingredients of the harvested product.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) that can be treated by the methods disclosed above include plants and plant cultivars with altered fiber characteristics, such as cotton plants. Such plants may be obtained by genetic transformation or by selection of plants comprising mutations conferring such altered fiber properties.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the methods disclosed above include plants and plant cultivars having altered oil profile characteristics, such as oilseed rape or related Brassica (Brassica) plants. Such plants may be obtained by genetic transformation or by selection of plants comprising mutations conferring such altered oil profile properties.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the methods disclosed above include plants and plant cultivars having altered seed shattering (shattering) characteristics, such as oilseed rape or related brassica plants. Such plants may be obtained by genetic transformation or by selection of plants comprising a mutation conferring such altered seed shatter characteristics, and include plants having a delayed or reduced seed shatter, such as oilseed rape plants.
Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) that can be treated by the methods disclosed above include plants and plant cultivars with altered post-translational protein modifications, such as tobacco plants.
Pathogens
Non-limiting examples of pathogens of fungal diseases that can be treated according to the present invention include:
diseases caused by powdery mildew pathogens, such as Blumeria species, such as Blumeria graminis (Blumeria graminis); sphaerotheca species (Podosphaera species), such as Podosphaera leucotricha (Podosphaera leucotricha); monocapsulata species (Sphaerotheca species), such as Sphaerotheca fuliginea (Sphaerotheca fuliginea); devil's claw species (Uncinula species), such as grape devil's claw (Uncinula necator);
Diseases caused by rust pathogens, such as species of the genus phakopsora, e.g., phakopsora fusca; camelina rust species, such as camelina coffea; phakopsora species, such as phakopsora pachyrhizi and phakopsora pomonensis; puccinia species, such as Puccinia recondita, Puccinia graminis or Puccinia tritici; single spore rust species, such as, for example, single spore rust of verrucosa;
diseases caused by pathogens selected from oomycetes, such as white rust species (Albugo species), such as white rust (algobo Candida); species of the genus Bremia (Bremia species), such as Bremia lactucae (Bremia lactucae); peronospora species (Peronospora species), such as Peronospora pisi (Peronospora pisi) or Peronospora brassicae (p.brassicae); phytophthora species (Phytophtora species), such as Phytophthora infestans (Phytophtora infestans); plasmopara species (Plasmopara species), such as Plasmopara viticola (Plasmopara viticola); pseudoperonospora species (Pseudoperonospora species), such as Pseudoperonospora humuli (Pseudoperonospora humuli) or Pseudoperonospora cubensis (Pseudoperonospora cubensis); pythium species (Pythium species), such as Pythium ultimum;
Leaf blight (leaf blight) and leaf wilting disease (leaf wilting disease) caused by the following pathogens: such as Alternaria species (Alternaria species), such as Alternaria solani (Alternaria solani); cercospora species (Cercospora species), such as, for example, Niurospora betanae (Cercospora betacola); cladosporium species (Cladosporum species), such as Cladosporium cucumerinum (Cladosporium cupreum); cochliobolus species (Cochliobolus species), such as Cochliobolus graminis (Cochliobolus sativus) (conidia form: Demodex entomospora (Drechslera), synonyms: Helminthosporium (Helminthosporium)) or Cochliobolus miyabenus (Cochliobolus miyabenus); anthrax species (Colletotrichum species), such as Phaseolus vulgaris (Colletotrichum lindemumanium); corynebacterium species (Corynebacterium species), such as, for example, Corynebacterium polyspora (Corynebacterium cassicola); species of the genus Puccinia (Cycloconium species), such as the species Epilobium oleaefolium (Cycloconium oleaginum); species of Diaporthe species (Diaporthe species), such as citrus Diaporthe citri (Diaporthe citri); elsinoe species (Elsinoe species), such as Elsinoe fabacearum (Elsinoe fawcettii); discophora species (Gloeosporium species), such as Gloeosporium discophorum (Gloeosporium laetiicolor); pleurotus species (Glomerella species), such as Pleurotus circulans (Glomerella cingulata); species of the species coccobacillus (Guignardia species), such as the species gluconococcus viticola (Guignardia bidwelli); leptosphaeria species (Leptosphaeria speces), such as Leptosphaeria maculans (Leptosphaeria maculans); megalocalcanthium species (Magnaporthe species), such as Magnaporthe grisea; aschersonia species (Microdochium species), such as for example, Aschersonia cerealis (Microdochium nivale); mycosphaerella species (Mycosphaerella species), such as Mycosphaerella graminicola (Mycosphaerella graminicola), Mycosphaerella arachidis (Mycosphaerella arachidicola) or Mycosphaerella fijiensis (Mycosphaerella fijiensis); darkling coccoid species (phaesperaceae), such as, for example, Rhizoctonia graminis (phaesperaceae nodorum); pyrenophora species (Pyrenophora species), such as Pyrenophora teres (Pyrenophora teres) or Pyrenophora tritici-repentis (Pyrenophora tritici repentis); species of the genus Podospora (Ramularia species), such as, for example, Ramularia collo-cygni (Ramularia collo-cygni) or Podospora viticola (Ramularia areola); rhinochloropsis species (Rhynchosporium species), such as Rhinochloropsis secalina (Rhynchosporium secalis); septoria species (Septoria species), such as Septoria apiacea (Septoria apii) or Septoria solani (Septoria lycopersii); species of the genus Spodospora (Stagonospora species), such as Stagonospora nodorum (Stagonospora nodorum); corallina species (Typhyla species), such as Corallina carolina (Typhyla incarnata); venturia species (Venturia species), such as Venturia inaequalis (Venturia inaqualis);
Root and stem diseases caused by the following pathogens: such as species of the genus, such as the species of the genus, for example, the species of the genus, Corticium graminearum (Corticium graminearum); fusarium species (Fusarium species), such as Fusarium oxysporum (Fusarium oxysporum); species of the genus Gaeumannomyces (Gaeumannomyces species), such as Gaeumannomyces graminis (Gaeumannomyces graminis); plasmodiophora species, such as Plasmodiophora brassicae; rhizoctonia species (Rhizoctonia species), such as Rhizoctonia solani (Rhizoctonia solani); species of the genus Scopulariopsis (Sarocladium species), such as Glochidiobolus oryzae (Sarocladium oryzae); sclerotinia species (Sclerotinium species), such as Sclerotinia oryzae (Sclerotinium oryzae), Tapesia species, such as Tapesia acuformis; rhinocerous species (Thielavirosis species), such as Rhinocerous rhizogenes (Thielavirosis basicola);
panicle and panicle diseases (including corn cobs) caused by the following pathogens: for example, an Alternaria species, such as an Alternaria species; aspergillus species (Aspergillus species), such as Aspergillus flavus (Aspergillus flavus); cladosporium species (Cladosporium species), such as, for example, Cladosporium cladonioides; claviceps species (Claviceps species), such as, for example, purple Claviceps (Claviceps purpurea); fusarium species, such as Fusarium culmorum; gibberella species (Gibberella species), such as Gibberella zeae; species of the genus Thermoascus (monographalella species), such as, for example, Fusarium nivale (monographalella nivalis); species of the genus Stagnospora, such as Stagnospora nodorum;
Diseases caused by smut fungi, such as species of the genus Sphacelotheca (Sphacelotheca species), such as Sphacelotheca reiliana; tilletia species (Tilletia species), such as Tilletia tritici (Tilletia caries) or Tilletia controversa (Tilletia controversa); ustilago species (Urocystis species), such as, for example, Ustilago occulta (Urocystis occulta); ustilago species (Ustilago species), such as Ustilago nuda;
fruit rot caused by the following pathogens: for example, Aspergillus species, such as Aspergillus flavus; botrytis species (Botrytis species), such as Botrytis cinerea (Botrytis cinerea); species of the genus Streptomyces (Monilinia species), such as, for example, Sclerotinia sclerotiorum (Monilinia laxa); penicillium species (Penicillium species), such as Penicillium expansum (Penicillium expandanum) and Penicillium purpurogenum (Penicillium purpurogenum); rhizopus species (Rhizopus species), such as Rhizopus stolonifer (Rhizopus stolonifer); sclerotinia species (Sclerotinia species), such as Sclerotinia sclerotiorum (sclerotiorum); verticillium species (Verticillium species), such as Verticillium alboatrum (Verticillium alboatrum);
Seed-and soil-borne rot and wilting diseases caused by the following pathogens, and seedling diseases: such as Alternaria species, for example, Alternaria brassicolo; species of the genus Saccharomycopsis (Aphanomyces species), such as, for example, Rhizoctonia solani (Aphanomyces euteiches); ascochyta species (Ascochyta species), such as, for example, Bisporum lentinus (Ascochyta lentis); aspergillus species, such as Aspergillus flavus; cladosporium species, such as Cladosporium herbarum (Cladosporium herbarum); species of the genus Sporidiobolus, such as, for example, Sporidiobolus graminis (conidia form: Helminthosporium, Helminthosporium (Bipolaris), synonyms: Helminthosporium); anthrax species, such as Colletotrichum coccoides (Colletotrichum coccodes); fusarium species, such as fusarium flavum; gibberella species, such as gibberella zeae; septoria species (macrophosta species), such as, for example, Septoria phaseoloides (macrophosia phaseolina); aschersonia species (Microdochium species), such as for example, Aschersonia cerealis (Microdochium nivale); a species of the genus, such as, for example, Curvularia nivales; penicillium species, such as penicillium expansum; phoma species (Phoma species), such as Phoma nigricans (Phoma linggam); phomopsis species (Phomopsis species), such as Phomopsis sojae; phytophthora species, such as Phytophthora infestans (Phytophthora cactorum); pyrenophora species, such as Pyrenophora graminea (Pyrenophora graminea); pyricularia species (Pyricularia species), such as Pyricularia oryzae (Pyricularia oryzae); pythium species, such as pythium ultimum; rhizoctonia species, such as rhizoctonia solani; rhizopus species, such as Rhizopus oryzae (Rhizopus oryzae); sclerotium species, such as Sclerotium rolfsii (Sclerotium rolfsii); septoria species, such as Septoria nodorum (Septoria nodorum); corallina species, such as Corallina sarcopora; verticillium species (Verticillium species), such as Verticillium dahliae (Verticillium dahliae);
Cancerous diseases, galls and broom diseases caused by the following pathogens: such as species of the genus Nectria (Nectria species), such as, for example, Nectria carinata (Nectria galligena);
wilting disease caused by the following pathogens: such as species of the genus Verticillium, for example Verticillium longisporarum (Verticillium longisporarum); fusarium species, such as fusarium oxysporum;
malformations of leaves, flowers and fruits caused by the following pathogens: for example, species of the genus Exobasidium (Exobasidium species), such as Exobasidium putida (Exobasidium vexans); exophiala species (Taphrina species), such as, for example, Exophiala malformates (Taphrina formals);
degenerative diseases of woody plants caused by the following pathogens: such as species of the genus Esca (Esca species), for example, Phaeniella chlamydospora (Phaemoniaella chlamydospora), Acremonium fusca (Phaeoacremonium alephium) or Porphyromonas mediterranei (Fomitosporidium mediterrana); ganoderma species (Ganoderma species), such as Ganoderma boninense (Ganoderma boninense);
diseases of plant tubers caused by the following pathogens: such as a Rhizoctonia species, such as Rhizoctonia solani; helminthosporium species, such as Helminthosporium solani (Helminthosporium solani);
Diseases caused by the following bacterial pathogens: such as species of the genus Xanthomonas (Xanthomonas species), such as Xanthomonas oryzae var alba (Xanthomonas campestris pr. oryzae); pseudomonas species, such as Pseudomonas syringae Cucumis sativus var (Pseudomonas syringae pv. lachrymans); erwinia species (Erwinia species), such as Erwinia amylovora (Erwinia amylovora); species of the genus Brevibacterium (Liberibacter species), such as the species of the genus Brevibacterium Asiatica (Liberibacter asiaticus); xylem species (Xyella species), such as xylem fastidiosa (Xylella fastidiosa); laurella species (Ralstonia species), such as Laurella solanacearum (Ralstonia solanacearum); dickeya species, such as Dickeya solani; corynebacterium species (Clavibacter species), such as Corynebacterium melampuritus (Clavibacter microorganisnsis); streptomyces species, such as Streptomyces scabies (Streptomyces scabies).
Soybean diseases:
fungal diseases of leaves, stems, pods and seeds caused by the following pathogens: such as Alternaria leaf spot (Alternaria leaf spot), Anthracnose (Anthracnose) (Colletotrichum gloeosporioides flat head variant (Colletotrichum gloeosporides flat head), brown spot (brown spot) (Septoria glaucophylla), Cercospora leaf spot and leaf blight (Cercospora leaf spot and blue) (Cercospora kikuchi)), Cercospora leaf spot (Choosepora leaf spot) (Choosepora innoAND blue) (Chooseria leaf spot (Hokuchi), Cercospora leaf spot (Chooseria leaf spot) (Chooseria Indorifera subfamila (Homophila)), Cercospora leaf spot (Pseudoperonospora leaf spot) (Pseudoperonospora leaf spot (Leptomyces), and Rhizoctonia solani (Pseudonocerophyma) leaf spot (Pseudoperonospora leaf spot), Rhizoctonia leaf spot (Pseudoperonospora solani) (Pseudoperonospora leaf spot (Pseudoperonospora solani) (Pseudoperonospora leaf spot), Rhizoctonia (Pseudoperonospora solani (Pseudoperonospora leaf spot), Rhizoctonia (Pseudoperonospora leaf spot (Pseudoperonospora leaf spot), Rhizoctonia (Pseudoperonospora) and Rhizoctonia (Pseudoperonospora leaf spot), Rhizoctonia (Pseudoperonospora leaf spot (Pseudoperonospora leaf spot), Rhizoctonia (Rhizoctonia) and Rhizoctonia (Rhizoctonia) of Rhizoctonia (Rhizoctonia) of Rhizoctonia), Rhizoctonia (Rhizoctonia), Rhizoctonia) of Rhizoctonia (Rhizoctonia) of Rhizoctonia), Rhizoctonia (Rhizoctonia) of Rhizoctonia (Rhizoctonia), Rhizoctonia (Rhizoctonia) of Rhizoctonia), Rhizoctonia (Rhizoctonia) of Rhizoctonia (Rhizoctonia), Rhizoctonia (Rhizoctonia) of Rhizoctonia (Rhizoctonia) of Rhizoctonia), Rhizoctonia) of Rhizoctonia (Rhizoctonia), Rhizoctonia) of Rhizoctonia (Rhizoctonia), Rhizoctonia (Rhizoctonia), Rhizoctonia (Rhizoctonia, Pod and stem blight (phomopsis sojae), powdery mildew (powdery mildew) (microphaga diffusa), acanthosporium leaf spot (Pyrenochaeta leaf spot) (Pyrenochaeta glycerins), Rhizoctonia aeroginosa (rhizoctonia solani), leaf blight and damping off (web blight) (Rhizoctonia solani), rust disease (phakopsora pachyrhizi, Hirudita manillensis), scab disease (scab) (spora glycines), Stachybotrys leaf blight (Stehlium leaf blast) (Stachybotrys botrytis (Stemphylium botrytis)), sudden death syndrome (Fusarium virguliforme), target spot (targetsite spot) (Polypopulus polystachys).
Root and shoot base fungal diseases caused by the following pathogens: such as black root rot (black rot) (lilium brownii (calodictyonia crispa)), carbon rot (charomycota (chayol rot) (phaeophycocystis phaseoloides), Fusarium wilt or wilting disease, root rot and pod and root rot (Fusarium oxysporum, Fusarium tricholobus (Fusarium orthoceras), Fusarium semitectum (Fusarium semitectum), Fusarium equiseti (Fusarium equiseti)), mycophylium root rot (mycophylium terrestris), neocaryophyllum (neospora) attack (neomyces versicolor), and stem rot (trichophycocephalum blight (trichophyceae), soybean ulcer (Phytophthora grandis), soybean stem rot (Phytophthora blight (Phytophthora capsici), soybean stem rot (Phytophthora grandis), soybean stem rot (Phytophthora blight (Phytophthora grandis) Pythium debaryanum (Pythium debaryanum), Pythium neprilowii (Pythium myriomycum), Pythium ultimum), Rhizoctonia root rot, stalk rot and damping-off (Rhizoctonia solani), Sclerotium stem rot (Sclerotium sclerotiorum), Sclerotinia sclerotiorum southern blight (sclerotium sclerotiorum), Rhinoceroma rhizorot (Rhinoconospora rhizoctonus).
Mycotoxins
In addition, the compounds of formula (I) and compositions comprising the same may reduce mycotoxin levels in harvested materials and food and feed products made therefrom. Mycotoxins include in particular, but are not limited to, the following: deoxynivalenol (DON), nivalenol (nivalenol), 15-Ac-DON, 3-Ac-DON, T2-toxin and HT 2-toxin, fumonisin (fumonisin), zearalenone (zearalenone), moniliformin (moniliformin), fusarin (fusarin), serpentine (diacetoxicinol) (DAS), beauvericin (beauvericin), fusarin (enniatin), fusarium (fusaroliferalin), fusarium alcohol (fusarenol), ochratoxin (ochratoxin), patulin (ergot alkaloid) and aflatoxin (lataflatoxin), which can be produced, for example, by: fusarium species, such as fusarium acuminatum (f.acuminatum), fusarium asiae (f.asiticum), fusarium avenaceum (f.avenaceum), fusarium crookwellense (f.crookwellense), fusarium flavum, fusarium graminearum (f.graminearum) (gibberella zeae), fusarium equiseti, fusarium luteorum (f.fujikoi), fusarium banana (f.musarum), fusarium oxysporum, fusarium exuberculosum (f.proliferum), fusarium pearinospora (f.poae), fusarium pseudograminearum (f.soudredomainum), fusarium sambucinum (f.sambucinum), fusarium scirpum (f.scirperi), fusarium semitectum, fusarium solani (f.sorarium), fusarium solani (f.sp.culorum), fusarium solanum moniliforme (f.sp.f.), fusarium solanum trichothecoides, fusarium solanum sp.f.f.e.f.f.f.f.; and aspergillus species, such as aspergillus flavus, aspergillus parasiticus (a. parasiticus), aspergillus nidulans (a. nomius), aspergillus ochraceus (a. ochraceus), aspergillus clavatus (a. clavatus), aspergillus terreus (a. terreus), aspergillus versicolor (a. versicolor); penicillium species, such as penicillium verrucosum (p. verrucosum), penicillium purrocyanium (p.viridicatum), penicillium citrinum (p.citrinum), penicillium expansum, penicillium clavatum (p.claviferme), and penicillium rocarburium (p.roqueforti); ergot species, such as, for example, ergot purpurea, ergot fusiformis (c.fusiformis), ergot paspali (c.paspali), ergot africana (c.africana); stachybotrys species (Stachybotrys spec.) and others.
Material protection
The compounds of formula (I) and compositions comprising them are also useful for material protection, in particular for protecting industrial materials from attack and destruction by phytopathogenic fungi.
Furthermore, the compounds of formula (I) and compositions comprising them can be used as antifouling compositions, alone or in combination with other active ingredients.
In this context, it is intended that,industrial materialsIt is understood to mean inanimate materials prepared for industrial use. For example, industrial materials that can be protected from microbial alteration or destruction can be adhesives, glues, paper, wallpaper and wood/cardboard, textiles, carpets, leather, wood, fibers and tissue, coatings and plastic articles, cooling lubricants and other materials that can be infected or destroyed by microorganisms. Within the scope of the materials to be protected, mention may also be made of parts of production plants and buildings which can be damaged by the proliferation of microorganisms, such as cooling water circuits, cooling and heating systems and ventilation and air-conditioning units. In the present inventionWithin the scope of the present invention, industrial materials preferably include adhesives, sizes, paper and card, leather, wood, coatings, cooling lubricants and heat transfer fluids, more preferably wood.
The compounds of formula (I) and compositions comprising the same can prevent adverse effects such as decay, spoilage, discoloration, or mold.
In the case of wood treatment, the compounds of formula (I) and compositions comprising them may also be used to combat fungal diseases susceptible to growth on or in wood.
Wood materialAll types of wood species and all types of work of the wood used for construction are meant, such as solid wood, high density wood, laminated wood and plywood. Furthermore, the compounds of formula (I) and compositions comprising the same are useful for protecting objects in contact with salt or brackish water, in particular ship hulls, screens, nets, buildings, moorings and signalling systems, from contamination.
The compounds of formula (I) and compositions comprising them are also useful for protecting storage articles. Storage articles are understood to mean natural substances of plant or animal origin or processed products thereof, which are of natural origin and require long-term protection. Storage goods of plant origin, for example plants or plant parts, such as stems, leaves, tubers, seeds, fruits, grains, can be protected immediately after harvesting or after processing by (pre) drying, moistening, comminuting, grinding, pressing or baking. Storage articles also include wood, including raw wood (e.g., construction lumber, utility poles, and fences) or wood in finished form (e.g., furniture). Storage articles of animal origin are, for example, hides, leather, skins and hair. The compounds of formula (I) and compositions comprising the same can prevent adverse effects such as decay, spoilage, discoloration, or mold.
Microorganisms capable of degrading or altering industrial materials include, for example, bacteria, fungi, yeasts, algae, and slime organisms (slime organisms). The compounds of formula (I) and compositions comprising them preferably act on fungi, in particular moulds, wood-discoloring and wood-destroying fungi (ascomycetes, basidiomycetes, deuteromycetes and zygomycetes), and on slime organisms and algae. Examples include microorganisms of the following genera: alternaria, such as Alternaria tenuis (Alternaria tenuis); aspergillus, such as Aspergillus niger; chaetomium, such as Chaetomium globosum (Chaetomium globosum); phanerochaete (Coniophora), such as Coniophora puetana; lentinus (Lentinus), for example Lentinus tigrinus (Lentinus tigrinus); penicillium, such as Penicillium glaucum; polyporus (Polyporus), such as Polyporus versicolor; aureobasidium (Aureobasidium), such as Aureobasidium pullulans; the genus Sclerophoma (Sclerophoma), such as Sclerophoma pitypophila; trichoderma, such as Trichoderma viride; the species Humicola spp, Pectinophora spp, Cladosporium spp, Coriolus spp, Gloeophyllum spp, Pleurotus spp, Porphyromyces spp, Rhizoctonia spp, Tyrophora spp, Tyroplus spp, Cladosporus spp, Penicillium spp, Escherichia coli, etc.; pseudomonas, such as Pseudomonas aeruginosa (Pseudomonas aeruginosa); staphylococci (Staphylococcus aureus), such as Staphylococcus aureus (Staphylococcus aureus), Candida species (Candida spp.) and Saccharomyces species (Saccharomyces spp.), such as Saccharomyces cerevisiae (Saccharomyces cerevisiae).
Seed treatment
The compounds of formula (I) and compositions comprising the same may also be used to protect seeds from unwanted microorganisms, such as phytopathogenic microorganisms (e.g., phytopathogenic fungi or phytopathogenic oomycetes). As used herein, the term "One or A plurality of seeds"includes dormant seeds, pregerminated seeds (primed seeds), pregerminated seeds and seeds in which roots and leaves have appeared.
The present invention therefore also relates to a method for protecting a seed from undesired microorganisms, said method comprising the step of treating the seed with a compound or composition of formula (I).
Treatment of seeds with a compound or composition of formula (I) not only protects the seeds from phytopathogenic microorganisms, but also protects the germinated seeds, emerging seedlings and the plants after emergence from the treated seeds. The invention therefore also relates to a method for protecting seeds, germinating seeds and emerging seedlings.
The seed treatment may be performed before, at or shortly after sowing.
When seed treatment is carried out before sowing (for example so-called dressing application), the seed treatment can be carried out as follows: the seed may be placed in a mixer containing the desired amount of the compound or composition of formula (I) and the seed and the compound or composition of formula (I) mixed until a uniform distribution on the seed is achieved. If appropriate, the seeds can then be dried.
The invention also relates to seeds coated with a compound of formula (I) or a composition comprising the same.
Preferably, the seed is treated in a state where the seed is sufficiently stable to not be damaged during the treatment. In general, the seeds may be treated at any time between harvest and shortly after sowing. Seeds that have been separated from the plant and have had the cob, husk, stalk, bark, hair or pulp removed are typically used. For example, seeds that have been harvested, cleaned and dried to a moisture content of less than 15% by weight may be used. Alternatively, it is also possible to use seeds which have been treated, for example, with water after drying and then dried again, or seeds immediately after pregermination (priming), or seeds stored in pregermination conditions or pre-germinated seeds, or seeds sown on nursery trays (tray), tape (tape) or paper.
The amount of the compound of formula (I) or composition comprising it applied to the seed is generally such that germination of the seed is not impaired, or the growing plant is not impaired. This must be ensured in particular in the case where the compounds of the formula (I) exhibit phytotoxic effects at a certain application rate. In determining the amount of compound of formula (I) to be applied to the seed, the inherent phenotype of the transgenic plant should also be taken into account in order to achieve optimal seed and germinating plant protection with a minimum amount of compound used.
The compound of formula (I) may be applied directly to the seed as such, i.e. without the use of any other components and without dilution. The composition comprising it may also be applied to seeds.
The compounds of formula (I) and compositions comprising them are useful for protecting seeds of any plant variety. Preferred seeds are seeds of the following plants: cereals (e.g. wheat, barley, rye, millet, triticale and oats), oilseed rape, corn, cotton, soybean, rice, potato, sunflower, beans, coffee, peas, sugar beets (e.g. sugar beets and fodder beets), peanuts, vegetables (e.g. tomatoes, cucumbers, onions and lettuce), turf grasses and ornamentals. More preferably wheat, soybean, rape, corn and rice seeds.
The compounds of formula (I) and compositions comprising them are useful for treating transgenic seed, particularly seed of plants capable of expressing polypeptides or proteins that act on pests, herbicide damage or abiotic stress, to enhance protection. Seeds of plants capable of expressing a polypeptide or protein that acts on a pest, herbicide damage or abiotic stress may comprise at least one heterologous gene that causes the polypeptide or protein to be expressed. These heterologous genes in the transgenic seed can be derived from microorganisms of, for example, the following genera: bacillus (Bacillus), Rhizobium, Pseudomonas, Serratia (Serratia), Trichoderma, Corynebacterium, Gliocladium, or Gliocladium. These heterologous genes are preferably derived from Bacillus species, in which case the gene products are effective against European corn borer and/or Western corn rootworm. Particularly preferably, the heterologous gene is derived from bacillus thuringiensis.
Administration of
The compounds of formula (I) may be administered as such, or for example in the form of: ready-to-use solutions, emulsions, aqueous or oil-based suspensions, powders, wettable powders, pastes, soluble powders, dusts, soluble granules, granules for broadcasting, suspoemulsion concentrates, natural products impregnated with a compound of formula (I), synthetic substances impregnated with a compound of formula (I), fertilizers and microcapsules in polymers.
Application is carried out in a conventional manner, for example by pouring, spraying, atomizing, broadcasting, dusting, foaming, spreading, etc. The compounds of formula (I) can also be applied by ultra-low volume methods, by drip irrigation systems or by dip application, in-furrow application or by injecting them into the stems or trunks of the soil. The compounds of formula (I) may also be applied by wound sealing, coating or other wound dressing.
The effective and plant compatible amount of a compound of formula (I) applied to a plant, plant part, fruit, seed or soil will depend on a variety of factors, such as the compound/composition used, the object of treatment (plant, plant part, fruit, seed or soil), the type of treatment (dusting, spraying, dressing), the purpose of the treatment (therapeutic and protective), the type of microorganism, the stage of development of the microorganism, the sensitivity of the microorganism, the stage of crop growth and the environmental conditions.
When using the compounds of the formula (I) as fungicides, the application rates can be varied within a wide range, depending on the type of application. For the treatment of plant parts (e.g. leaves), the application rate can be from 0.1 to 10000g/ha, preferably from 10 to 1000g/ha, more preferably from 50 to 300g/ha (in the case of application by watering or drip application, the application rate can even be reduced, especially when inert substrates such as rockwool or perlite are used). For the treatment of seeds, the application rate may be from 0.1 to 200g per 100kg of seeds, preferably from 1 to 150g per 100kg of seeds, more preferably from 2.5 to 25g per 100kg of seeds, even more preferably from 2.5 to 12.5g per 100kg of seeds. For the treatment of the soil, the application rate can be from 0.1 to 10000g/ha, preferably from 1 to 5000 g/ha.
These application rates are examples only and are not intended to limit the scope of the present invention.
Various aspects of the present teachings may be further understood in light of the following examples, which should not be construed as in any way limiting the scope of the present teachings.
Examples
Overview (general)
Measurement of LogP value
The measurement of LogP values provided herein was performed by HPLC (high performance liquid chromatography) on reverse phase columns according to EEC directive 79/831 annex v.a8 using the following method:
[a]the LogP value was determined by LC-UV measurement in the acidic range using 0.1% aqueous formic acid and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95% acetonitrile).
[b]LogP values were determined by LC-UV measurements in the neutral range using 0.001 molar aqueous ammonium acetate and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95% acetonitrile).
[c]LogP values were determined by LC-UV measurements in the acidic range using 0.1% phosphoric acid and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95% acetonitrile).
If more than one LogP value is available in the same method, all values are given and separated by "+".
Calibration was performed with linear alk-2-ones (having 3 to 16 carbon atoms) with known LogP values (LogP values were measured using retention times using linear interpolation between successive alkanones). The lambda maximum was determined using the uv spectrum from 200nm to 400nm and the peak of the chromatographic signal.
1H-NMR data
Selected embodiments provided herein1H-NMR data of1The H-NMR peak list is written in formal writing. For each signal peak, the delta values in ppm are listed, and the signal intensities are listed in parentheses. The delta value-signal strength number pairs are separated by semicolons.
Thus, the peak list of one embodiment has the following form:
δ1(strength)1)；δ2(strength)2)；......；δi(strength)i)；......；δn(strength)n)
The intensity of the spike is highly correlated with the signal in cm in the printed example of the NMR spectrum and shows the true relationship of the signal intensities. From the broad-peak signal, several peaks or intermediate peaks of the signal and their relative intensities compared to the strongest signal in the spectrum can be shown.
To calibrate1Chemical shifts of the H spectrum, using tetramethylsilane and/or the solvent used, in particular in the case of the spectrum measured in DMSO. Thus, tetramethylsilane peaks may, but need not, appear in the NMR peak list.
1List of H-NMR peaks and convention1The H-NMR prints are similar and therefore typically contain all the peaks listed in the conventional NMR specification.
Furthermore, as is conventional1H-NMR prints which can show the solvent signal, the signal of the stereoisomer of the target compound (which is also subject of the present invention) and/or the signal of the impurity peaks.
In order to display the signal of the compound in the delta range of solvent and/or water1The conventional peaks of the solvent are shown in the list of H-NMR peaks, for example in DMSO-D6DMSO peak and water peak in (1), and generally have an average higher intensity.
The peaks of stereoisomers of the target compound and/or of impurities typically have an average lower intensity than the peaks of the target compound (e.g. with a purity of > 90%).
These stereoisomers and/or impurities may be unique to a particular method of preparation. Thus, their peaks can help identify the reproducibility of the manufacturing process by "side-products-fingerprints".
The practitioner calculates the peaks of the target compound by known methods (MestreC, ACD simulation, and using empirically evaluated expected values) and optionally uses additional intensity filters to separate the peaks of the target compound as needed. This separation is similar to conventional1The relevant peaks were picked up in the H-NMR specification.
Additional details of the description of NMR Data on peak lists can be found in the publication "circulation of NMR PeakList Data with Patent Applications" in the Research Disclosure Database (Research Disclosure Database) No. 564025.
The following examples illustrate in a non-limiting manner the preparation and biological activity of the compounds of formula (I) of the present invention.
Synthesis of Compounds of formula (I) and intermediates
Table 1 illustrates, in a non-limiting manner, examples of compounds of formula (I) according to the invention:
the compounds of formula (I) mentioned in table 1 below were prepared according to the procedures detailed below in connection with the specific examples and the general description of the methods disclosed herein.
In Table 1, logP values are according to method[a]And (4) measuring.
In Table 1, "#" represents the point of attachment of the divalent group A to the aromatic group, and "#" represents the divalent group A to the divalent group- [ CR ]1R2]m-and "represents a divalent group- [ CR 1R2]m-and R3The point of attachment of the group.
Table 3 provides NMR data for a selected number of compounds in tables 1 and 2: (1H)。
TABLE 3: list of NMR peaks
Preparation examples
Preparation of example 1: 5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl]-N- (1-phenylcyclobutyl) pyrimidin-2-amine (compound I.134)
Step 1: preparation of 2- [ (1-phenylcyclobutyl) amino]Pyrimidine-5-carboxylic acid ethyl ester
5.27g (40.8mmol) of N, N-diisopropylethylamine are added to a solution of 2.53g (13.6mmol) of ethyl 2-chloropyrimidine-5-carboxylate and 2.00g (13.6mmol) of 1-phenylcyclobutylamine in 15mL of 1, 4-dioxane at room temperature. The reaction mixture was stirred at 110 ℃ for 4 hours and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give 3.60g (97% purity, 86% yield) of ethyl 2- [ (1-phenylcyclobutyl) amino ] pyrimidine-5-carboxylate as a white solid. LogP ═ 3.53[ method a ]. Mass (M + H) ═ 298.
Step 2: preparation of 2- [ (1-phenylcyclobutyl) amino]Pyrimidine-5-carbohydrazide
2.29mL (98% purity, 46.3mmol) of hydrazine monohydrate are added to 700mg (2.35mmol) of 2- [ (1-phenylcyclobutyl) amino]Pyrimidine-5-carboxylic acid ethyl ester in 5mL ethanol solution. The reaction mixture was heated at 120 ℃ for 1 hour under microwave and concentrated under reduced pressure. The resulting mixture was diluted with water (10mL) and extracted with ethyl acetate (3 × 20 mL). The combined organic layers were washed with brine (10mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (gradient acetonitrile/water +10mmol/L NH) 4HCO3) Purification gave 650mg (97% purity, 95% yield) of 2- [ (1-phenylcyclobutyl) amino group as a pale yellow solid]Preparation of pyrimidine-5-carbohydrazide. LogP ═ 1.63[ method A ]]. Mass (M + H) is 284.
Step 3: preparation of N' - (difluoroacetyl) -2- [ (1-phenylcyclobutyl) amino]Pyrimidine-5-carbohydrazide
369mg (2.12mmol) of difluoroacetic anhydride are added at room temperature to a solution of 500mg (1.76mmol) of 2- [ (1-phenylcyclobutyl) amino ] pyrimidine-5-carbohydrazide and 268mg (2.65mmol) of triethylamine in 5mL of tetrahydrofuran. The reaction mixture was stirred at room temperature for 2 hours. The resulting mixture was diluted with water (10mL) and extracted with ethyl acetate (3 × 15 mL). The combined organic extracts were washed with brine (10mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by C18 silica gel column chromatography (gradient water/acetonitrile) to give 600mg (99% purity, 93% yield) of N' - (difluoroacetyl) -2- [ (1-phenylcyclobutyl) amino ] pyrimidine-5-carbohydrazide as a pale white solid. LogP ═ 1.99[ method a ]. Mass (M + H) — 362.
Step 4: 5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl]-N- (1-phenylcyclobutyl) pyrimidin-2-amine (C:)Compound I.134)
659mg (2.77mmol) of Bogis reagent (CAS 29684-56-8) are added to 500mg (1.38mmol) of N' - (difluoroacetyl) -2- [ (1-phenylcyclobutyl) amino]Pyrimidine-5-carbohydrazide in 5mL of tetrahydrofuran. The reaction mixture was heated at 150 ℃ for 1 hour under microwave. The resulting mixture was diluted with water (10mL) and extracted with ethyl acetate (3 × 15 mL). The residue was purified by preparative HPLC (gradient acetonitrile/water + 0.1% CF)3CO2H) Purification gave 200mg (99% purity, 42% yield) of N' - (difluoroacetyl) -2- [ (1-phenylcyclobutyl) amino]Pyrimidine-5-carbohydrazide. LogP ═ 3.18[ method A ]]. Mass (M + H) 344.
Preparation of example 2: 3-Ethyl-5- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl]Phenyl } -1, 2, 4-oxadiazole (Compound I.018)
Step 1: preparation of 2- [4- (3-ethyl-1, 2, 4-oxadiazol-5-yl) benzoyl]Hydrazine carboxylic acid tert-butyl ester
62mg (0.47mmol) of tert-butyl carbazate and 101mg (0.78mmol) of N, N-diisopropylethylamine are added to a solution of 85mg (0.39mmol) of 4- (3-ethyl-1, 2, 4-oxadiazol-5-yl) benzoic acid and 149mg (0.39mmol) of HATU (CAS 148893-10-1) in 3mL of dichloromethane. The reaction mixture was stirred at 40 ℃ for 7 hours and concentrated under reduced pressure. The residue was purified by preparative HPLC (gradient acetonitrile/water + 0.1% HCO) 2H) Purification gave 114mg (99% purity, 87% yield) of 2- [4- (3-ethyl-1, 2, 4-oxadiazol-5-yl) benzoyl in the form of a pale yellow solid]Tert-butyl hydrazinoformate. LogP ═ 1.23[ method A ]]. Mass (M + H) 333.
Step 2: preparation of 4- (3-Ethyl-1, 2, 4-oxadiazol-5-yl) -N' - (trifluoroacetyl) benzoylhydrazine (compound IIa.14)
0.5mL of trifluoroacetic acid (6.49mmol) was added to a solution of 312mg (0.94mmol) of tert-butyl 2- [4- (3-ethyl-1, 2, 4-oxadiazol-5-yl) benzoyl ] hydrazinecarboxylate in 1.5mL of dichloromethane. The reaction mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure to give the crude product. At room temperature, 0.14mL (0.99mmol) of trifluoroacetic anhydride was added to a solution of half of the crude product obtained previously in 4mL of dichloromethane. The reaction mixture was stirred at room temperature for 45 minutes and concentrated under reduced pressure to give 138mg (96% purity, 86% yield) of 4- (3-ethyl-1, 2, 4-oxadiazol-5-yl) -N' - (trifluoroacetyl) benzoyl hydrazine. LogP ═ 1.93[ method a ]. Mass (M + H) 329.
Step 3: preparation of 3-ethyl-5- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl]Phenyl } -1, 2, 4-oxadiazole (Compound I.018)
139mg (0.59mmol) of Bougies reagent (CAS 29684-56-8) are added at room temperature to a solution of 128mg (0.39mmol) of 4- (3-ethyl-1, 2, 4-oxadiazol-5-yl) -N' - (trifluoroacetyl) benzoylhydrazine in 1.5mL of tetrahydrofuran. The reaction mixture was stirred at 60 ℃ for 2 hours and concentrated under reduced pressure. The residue was purified by preparative HPLC (gradient acetonitrile/water + 0.1% HCO) 2H) Purification to give 35mg (99% purity, 29% yield) of 3-ethyl-5- {4- [5- (trifluoromethyl) -1, 3, 4-oxadiazol-2-yl as an off-white solid]Phenyl } -1, 2, 4-oxadiazole. LogP ═ 3.59[ method A ]]. Mass (M + H) 311.
Preparation of example 3: 4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl]Benzoic acid (Compound I.008)
Step 1: preparation of 4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl]Benzoic acid methyl ester (Compound I.011)
7.67g (18.9mmol) of Lawson's reagent (CAS 19172-47-5) were added under a nitrogen atmosphere to a solution of 5.0g (17.2mmol) of methyl 4- { [2- (trifluoroacetyl) hydrazino ] carbonyl } benzoate in 50mL of toluene at room temperature. The reaction mixture was stirred at 120 ℃ for 2 hours, cooled to room temperature and quenched by the addition of saturated aqueous sodium bicarbonate. The resulting mixture was extracted with ethyl acetate (2 × 100 mL). The combined organic layers were washed with brine (30mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give 4.0g (99% purity, 80% yield) of methyl 4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzoate as a white solid. LogP ═ 3.23[ method a ]. Mass (M + H) ═ 289.
Step 2: preparation of 4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl]Benzoic acid (Compound I.008)
2.86mL of lithium hydroxide solution (2.0M in tetrahydrofuran, 5.72mmol) was added to a solution of 1.10g (3.82mmol) of methyl 4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzoate in 5mL of a 1: 1 mixture of tetrahydrofuran and methanol. The reaction mixture was stirred at room temperature for 20 minutes and concentrated under reduced pressure. The resulting mixture was diluted with water (10mL) and acidified to pH 4 with 1M aqueous hydrochloric acid. The precipitated solid was collected by filtration and washed with water (2 × 10 mL). The resulting solid was dried in an oven under reduced pressure to give 600mg (97% purity, 56% yield) of 4- [5- (trifluoromethyl) -1, 3, 4-thiadiazol-2-yl ] benzoic acid as a white solid. LogP ═ 1.41[ method a ]. Mass (M + H) 275.
Preparation of example 4: 5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl]-N- [2- (4-fluorophenyl) propan-2-yl]Pyrimidine-2-amines (Compound I.150)
In a 2.5mL oven-dried microwave tube, 253mg (1.95mmol) of N, N-diisopropylethylamine was added to 100mg (0.65mmol) of 2- (4-fluorophenyl) -propan-2-amine and 159mg (0.68mmol) of 2-chloro-5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl ]-pyrimidine in 1mL dry dioxane. The reaction mixture was heated at 90 ℃ for 16 hours under microwave. The cooled reaction mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC (gradient acetonitrile/water +0. I% HCO)2H) Purification to give 145mg (98% purity, 62% yield) of 5- [5- (difluoromethyl) -1, 3, 4-oxadiazol-2-yl) in solid form]-N- [2- (4-fluorophenyl) propan-2-yl]Pyrimidin-2-amine. LogP ═ 3.26[ method A ]]. Mass (M + H) 350.
Biological examples
Example A: fungicidal activity against Phakospora pachirhizi
Cryopreserved (cryo-conserved) wild-type spores of the living vegetative organism (bioph) phakospora pachirizi were humidified overnight in the dark in a dedicated room at 18 ℃. The next day, in water-based growth medium (H)2O +0.2mM MOPS at pH 7+ 0.01% Tweenn 20) preparation of 7x103sp/mL spore solution and distribution of spores in 96-MTPS by means of a dispenser robot (final volume per well 200. mu.L). Each molecule was tested at 10 doses (final concentration from 30 to 0.002ppm) and thus 1.2 μ L of each dilution was transferred to a dedicated well with 0.6% DMSO in its final concentration. Wild type spores and molecules were incubated at 21 ℃ for 4 hours, and then 6 images per well were obtained using transmitted light images (Image Xpress Micro microscope, Molecular Devices, objective lens 10X, 6 images per well). The number of germinating spores per image was detected and quantified using a dedicated in-house development algorithm (MetaXpress software, Molecular Devices). Thus, inhibition of fungal germination was determined by comparing the number of germinating spores in wells containing the test compound with the number of germinating spores in wells containing no active ingredient.
In this test, the following compounds according to the invention show an efficacy of at least 70% at an active ingredient concentration of 30 ppm: i.04; I.018.
in this test, the following compounds according to the invention show an efficacy of at least 70% at an active ingredient concentration of 20 ppm: i.008; i.134; i.144; I.160.
in this test, the following compounds according to the invention show an efficacy of at least 70% at an active ingredient concentration of 4 ppm: I.027.
example B: in vitro cell assay for Colletotrichum phaseolorum (Colletotrichum lindemunianum)
Solvent: dimethyl sulfoxide
Culture medium: 14.6g of anhydrous D-glucose (VWR),
7.1g fungal peptone (Oxoid),
1.4g of granular yeast extract (Merck), 1 liter of QSP
Inoculum: spore suspension
The test compound was dissolved in dimethyl sulfoxide and the solution was used to prepare the desired concentration range. The final concentration of dimethyl sulfoxide used in the test is less than or equal to 1%.
A spore suspension of bean anthrax was prepared and diluted to the desired spore density.
The ability of the compounds to inhibit spore germination and hyphal growth was evaluated in liquid culture assays. The compound is added to the medium containing the spores at the desired concentration. After 6 days of incubation, compounds were assayed for fungal toxicity by spectrometric measurement of hyphal growth. Inhibition of fungal growth was determined by comparing the absorbance values in wells containing test compound to control wells containing no test compound.
In this test, the following compounds of the invention showed efficacy of 70% to 79% at a test compound concentration of 20 ppm: i.051; i.112; i.120; i.132; i.141; i.146; i.171; i.172; i.176; i.182; I.196.
in this test, the following compounds of the invention showed efficacy of 80% to 89% at a test compound concentration of 20 ppm: i.025; i.067; i.125; i.135; i.136; i.145; i.150; i.157; i.160; i.165; i.166; i.169; i.173; i.175; i.181; I.183.
in this test, the following compounds of the invention showed efficacy of 90% to 100% at a test compound concentration of 20 ppm: i.013; i.017; i.061; i.063; i.068; i.077; i.089; i.110; i.118; i.122; i.123; i.131; i.134; i.139; i.144; i.152; i.159; I.177.
example C: in vivo preventative testing of Botrytis cinerea (Gray mold)
Solvent: 5% by volume of dimethyl sulfoxide
10% by volume acetone
Emulsifier: 1 μ l80 per mg of active ingredient
Test compounds are tested in dimethyl sulfoxide/acetone/ml80, and then diluted in water to the desired concentration.
Young plants of gherkin or cabbage were treated by spraying with the test compounds prepared as described above. Based on acetone/dimethyl sulfoxide alone 80 to control plants.
After 24 hours, the plants were infected by spraying the leaves with an aqueous suspension of botrytis cinerea spores. Infected gherkin plants were incubated at 17 ℃ and 90% relative humidity for 4 to 5 days. Infected cabbage plants are incubated at 20 ℃ and 100% relative humidity for 4 to 5 days.
The test was evaluated 4 to 5 days after inoculation. 0% means an efficacy which corresponds to that of the control plants, whereas 100% efficacy means that no disease is observed.
In this test, the following compounds according to the invention show an efficacy of 70% to 79% at an active ingredient concentration of 500 ppm: i.077; i.135; i.153; i.161; i.170; I.181.
in this test, the following compounds according to the invention show an efficacy of 80% to 89% at an active ingredient concentration of 500 ppm: i.030; i.034; i.050; i.053; I.116.
in this test, the following compounds according to the invention show an efficacy of 90% to 100% at an active ingredient concentration of 500 ppm: i.045; i.076; i.113; i.123; i.146; I.196.
example D: in vivo prophylactic testing of puccinia recondita (brown rust of wheat)
Solvent: 5% by volume of dimethyl sulfoxide
10% by volume acetone
Emulsifier: 1 μ l 80 per mg of active ingredient
Test compounds are tested in dimethyl sulfoxide/acetone/ml80, then dissolved and homogenized in waterDiluting to the required concentration.
Young plants of wheat were treated by spraying with the test compounds prepared as described above. Based on acetone/dimethyl sulfoxide alone80 to control plants.
After 24 hours, the plants were infected by spraying the leaves with an aqueous suspension of puccinia recondita spores. Infected wheat plants were incubated at 20 ℃ and 100% relative humidity for 24 hours and then at 20 ℃ and 70-80% relative humidity for 10 days.
11 days after inoculation, the test was evaluated. 0% means an efficacy which corresponds to that of the control plants, whereas 100% efficacy means that no disease is observed.
In this test, the following compounds of the invention showed efficacy of 70% to 79% at a test compound concentration of 500 ppm: i.108; i.120; i.121; i.127; i.134; I.180.
in this test, the following compounds of the invention showed efficacy of 80% to 89% at a test compound concentration of 500 ppm: 026; i.118; i.132; i.136; I.155.
in this test, the following compounds of the invention showed efficacy of 90% to 100% at a test compound concentration of 500 ppm: i.093; i.122; i.125; i.133; i.137; i.144; i.145; i.146; i.150; i.156; i.157; i.165; i.166; i.175; i.177; I.181.
Example E: in vivo prophylactic testing of Alternaria brassicae (brassica oleracea)
Solvent: 5% by volume of dimethyl sulfoxide
10% by volume acetone
Emulsifier: 1 μ l80 per mg of active ingredient
Test compounds are tested in dimethyl sulfoxide/acetone/ml80, and then diluted in water to the desired concentration.
Young plants of brassica oleracea were treated by spraying with the test compound prepared as described above. Based on acetone/dimethyl sulfoxide alone80 to control plants.
After 24 hours, the plants were infected by spraying the leaves with an aqueous suspension of alternaria brassicae spores. Infected cabbage plants were incubated at 20 ℃ and 100% relative humidity for 6 days.
The test was evaluated 6 days after inoculation. 0% means an efficacy which corresponds to that of the control plants, whereas 100% efficacy means that no disease is observed.
In this test, the following compounds of the invention showed efficacy of 70% to 79% at a test compound concentration of 500 ppm: i.002; i.040; i.068; 072; i.133; i.150; i.157; i.166; I.175.
in this test, the following compounds of the invention showed efficacy of 80% to 89% at a test compound concentration of 500 ppm: i.007; i.017; i.105; i.171; i.172; I.177.
In this test, the following compounds of the invention showed efficacy of 90% to 100% at a test compound concentration of 500 ppm: i.005; i.010; i.013; i.045; i.076; i.087; i.094; i.110; i.113; i.131; i.135; i.137; i.146; i.147; i.156; i.170; I.196.
example F: in vivo preventative testing of phakopsora pachyrhizi (soybean)
Solvent: 5% by volume of dimethyl sulfoxide
10% by volume acetone
Emulsifier: 1 μ l80 per mg of active ingredient
Compounding the testObject in dimethyl sulfoxide/acetone/liver80, and then diluted in water to the desired concentration.
Young plants of wheat were treated by spraying with the test compounds prepared as described above. Based on acetone/dimethyl sulfoxide alone80 to control plants.
After 24 hours, the plants were infected by spraying the leaves with an aqueous suspension of phakopsora pachyrhizi spores. Infected soybean plants were incubated at 24 ℃ and 100% relative humidity for 24 hours and then at 24 ℃ and 70-80% relative humidity for 11 days.
12 days after inoculation, the test was evaluated. 0% means an efficacy which corresponds to that of the control plants, whereas 100% efficacy means that no disease is observed.
In this test, the following compounds of the invention showed efficacy of 70% to 79% at a test compound concentration of 500 ppm: i.009; i.115; I.171.
in this test, the following compounds of the invention showed efficacy of 80% to 89% at a test compound concentration of 500 ppm: I.147.
in this test, the following compounds of the invention showed efficacy of 90% to 100% at a test compound concentration of 500 ppm: i.019; 024; i.059; i.083; i.088; i.093; i.110; i.118; i.120; i.121; i.122; i.125; i.127; i.132; i.133; i.134; i.136; i.137; i.144; i.145; i.146; i.150; i.155; i.156; i.157; i.160; i.165; i.166; i.177; i.181; I.196.
example G: in vivo preventative testing of phakopsora pachyrhizi (soybean)
Solvent: 24.5 parts by weight of acetone
24.5 parts by weight of dimethylacetamide
Emulsifier: 1 part by weight of an alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried, the plants are inoculated with an aqueous suspension of spores of the causative agent of soybean rust (phakopsora pachyrhizi) and left to stand for 24 hours in an incubation chamber at about 24 ℃ and 95% relative atmospheric humidity in the absence of light.
Plants were maintained in an incubation chamber at about 24 ℃ and about 80% relative atmospheric humidity with a 12 hour day/night interval.
7 days after inoculation, the test was evaluated. 0% means an efficacy corresponding to the untreated control, while 100% efficacy means no disease observed.
In this test, the following compounds according to the invention show an efficacy of 90% to 100% at an active ingredient concentration of 250 ppm: i.134; I.165.
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