阅读说明：本技术 一类1，3，4-噁二唑酰肼类化合物及其制备方法和应用 (1, 3, 4-oxadiazole hydrazide compounds and preparation method and application thereof ) 是由 杨松 王培义 吴元元 朱建军 龙周卿 于 2020-04-24 设计创作，主要内容包括：本发明涉及一类1,3,4-噁二唑酰肼类化合物及其制备方法和应用。该化合物具有如通式(I)所示的结构：<Image he="331" wi="424" file="DSA0000207376320000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明以1,3,4-噁二唑类化合物为基础,将酰肼引入到此体系中,该化合物对植物致病病原细菌、真菌及卵菌具有良好的抑制作用,针对病原菌如水稻白叶枯病菌、小麦赤霉病菌、辣椒枯萎病菌、油菜菌核病菌、油菜炭疽病菌、马铃薯晚疫病菌和蓝莓根腐病菌等具有良好的抑制效果。(The invention relates to a 1, 3, 4-oxadiazole hydrazide compound and a preparation method and application thereof. The compound has a structure shown as a general formula (I):)

1. 1, 3, 4-oxadiazole hydrazide compound or a stereoisomer thereof, or a salt or solvate thereof, wherein: the compound has a structure shown as a general formula (I):

wherein R is₁Independently selected from one or more of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, hydroxyl, amino, halogen, mercapto, phosphino, nitro, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl；

R₂Independently selected from hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl.

2. The 1, 3, 4-oxadiazole hydrazide compound or a stereoisomer thereof, or a salt or solvate thereof according to claim 1, wherein:

R₁independently selected from one or more of hydrogen, deuterium, alkyl, alkoxy, hydroxyl, amino, nitro, halogen, mercapto, phosphino, aryl or heteroaryl; preferably, R₁Independently selected from hydrogen, deuterium, C₁-C₆Alkyl radical, C₁-C₆Alkoxy, hydroxy, amino, nitro, halogen, mercapto, phosphino, C₆-C₁₀Aryl or C₅-C₁₀One or more of heteroaryl; more preferably, R₁Independently selected from one or more of hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, hydroxyl, amino, nitro, F, Cl, Br, phenyl, benzyl, pyridyl, furanyl, thienyl, chlorophenyl, fluorophenyl, bromophenyl, methoxyphenyl, methylphenyl, ethylphenyl, 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, 1, 4-dichlorophenyl, 1, 2-dibromophenyl, 1, 3-dibromophenyl, 1, 4-dibromophenyl, 1, 2-difluorophenyl, 1, 3-difluorophenyl, 1, 4-difluorophenyl; most preferably, R1 is independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, hydroxy, amino, nitro, F, Cl, Br, phenyl, furyl, thienyl, chlorophenyl, fluorophenyl, bromophenyl, methoxyphenyl, methylphenyl, ethylphenyl, 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, 1, 4-dichlorophenyl, 1, 2-dibromophenyl, 1, 3-dibromophenylOne or more of bromophenyl, 1, 4-dibromophenyl, 1, 2-difluorophenyl, 1, 3-difluorophenyl, 1, 4-difluorophenyl;

R₂independently selected from one or more of hydrogen, deuterium, alkyl, alkoxy, cycloalkyl, amino, aryl or heteroaryl; preferably, R₂Independently selected from hydrogen, deuterium, C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₃-C₈Cycloalkyl, amino, C₆-C₁₀Aryl or C₅-C₁₀One or more of heteroaryl; more preferably, R₂Independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, pyridyl, furyl, thienyl, chlorophenyl, fluorophenyl, bromophenyl, methoxyphenyl, methylphenyl, ethylphenyl, trifluoromethylphenyl, nitrophenyl, 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, 1, 4-dichlorophenyl, 1, 2-dibromophenyl, 1, 3-dibromophenyl, 1, 4-dibromophenyl, 1, 2-difluorophenyl, 1, 3-difluorophenyl, 1, 4-difluorophenyl, o, 1, 2-dimethylphenyl, 1, 3-dimethylphenyl, 1, 4-dimethylphenyl, 1, 2, 4, 5-tetrafluorophenyl, 1, 2, 3, 4-tetrafluorophenyl, 1, 2, 3, 5-tetrafluorophenyl, 1, 2, 4, 5-tetrachlorophenyl, 1, 2, 3, 4-tetrachlorophenyl, 1, 2, 3, 5-tetrachlorophenyl; most preferably, R2 is independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, pyridyl, furyl, thienyl, chlorophenyl, fluorophenyl, bromophenyl, methoxyphenyl, methylphenyl, ethylphenyl, trifluoromethylphenyl, nitrophenyl, 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, 1, 4-dichlorophenyl, 1, 2-dibromophenyl, 1, 3-dibromophenyl, 1, 4-dibromophenyl, 1,2-difluorophenyl group, 1, 3-difluorophenyl group, 1, 4-difluorophenyl group,

1, 2-dimethylphenyl, 1, 3-dimethylphenyl, 1, 4-dimethylphenyl, 1, 2, 4, 5-tetrafluorophenyl, 1, 2, 3, 4-tetrafluorophenyl, 1, 2, 3, 5-tetrafluorophenyl, 1, 2, 4, 5-tetrachlorophenyl, 1, 2, 3, 4-tetrachlorophenyl, 1, 2, 3, 5-tetrachlorophenyl.

3. The 1, 3, 4-oxadiazole hydrazide compound or a stereoisomer thereof, or a salt or solvate thereof according to claim 1, wherein the compound is selected from the following specific compounds:

4. an intermediate compound for preparing the compound of claim 1 or a stereoisomer thereof, or a salt or solvate thereof, characterized by the following:

wherein R is₁As claimed in claim 1.

5. A process for preparing a compound of claim 1 or a stereoisomer thereof, or a salt or solvate thereof, comprising the steps of:

and R₂-NHNH₂Reacting to produce the compound of formula (I).

6. The method of claim 5, further comprising the steps of:

7. a composition comprising a compound of claim 1 or a salt thereof

A stereoisomer, or a salt or solvate thereof, and an agriculturally acceptable adjuvant or fungicide, insecticide or herbicide; preferably, the formulation of the composition is selected from Emulsifiable Concentrates (EC), Dusts (DP), Wettable Powders (WP), Granules (GR), Aqueous Solutions (AS), Suspension Concentrates (SC), ultra low volume sprays (ULV), Soluble Powders (SP), Microcapsules (MC), smoking agents (FU), aqueous Emulsions (EW), water dispersible granules (WG).

8. Use of a compound of claim 1 or a stereoisomer thereof, or a salt or solvate thereof, or a composition of claim 7, for controlling an agricultural pest, preferably a bacterial or fungal disease of a plant; more preferably, the agricultural pests are plant leaf blight and plant canker; most preferably, the agricultural pests are rice bacterial leaf blight, cucumber bacterial leaf blight, konjac bacterial leaf blight, citrus canker, grape canker, tomato canker, kiwi canker, apple canker, cucumber gray mold, pepper wilt, rape sclerotinia rot, wheat scab, potato late blight, and blueberry root rot.

9. A method for controlling agricultural pests is characterized in that: allowing the compound according to claim 1 or a stereoisomer thereof, or a salt or solvate thereof, or the composition according to claim 7 to act on harmful substances or their living environments; preferably, the agricultural pest is a bacterial or fungal disease of a plant; more preferably, the agricultural pests are rice bacterial leaf blight, tobacco bacterial wilt, cucumber bacterial leaf blight, konjak bacterial leaf blight, citrus canker, grape canker, tomato canker, kiwi canker, apple canker, cucumber gray mold, pepper wilt, rape sclerotinia rot, wheat scab, potato late blight and blueberry root rot.

10. A method for protecting a plant from an agricultural pest comprising a method step wherein the plant is contacted with a compound of claim 1 or a stereoisomer thereof, or a salt or solvate thereof, or a composition of claim 7.

Technical Field

The invention relates to the technical field of medicinal chemistry, and discloses a compound containing 1, 3, 4-oxadiazole hydrazide, and a preparation method and application thereof.

Background

Pesticides, as organic substances with specific biological activity, are used to influence, control and regulate the growth, development and reproduction processes of various agricultural pests to ensure the yield and safety of grain and cash crops worldwide. However, since the resistance of conventional pesticides is gradually increased, development of efficient, low-toxic, and low-residue green pesticides is urgently required.

Heterocyclic compounds have the characteristics of structural diversity and biological activity diversity, and attract extensive attention in the fields of medicinal chemistry, agrochemical chemistry and organic chemistry. The oxadiazole compound has broad-spectrum medical and pesticide biological activity, 1, 3, 4-oxadiazole is one of the most representative structures in the oxadiazole compound, and the biological activity comprises sterilization, antivirus, weeding, disinsection, antioxidation, anti-inflammation, anticancer, antimalarial, antitumor, antitubercular, anti-AIDS and the like.

On the other hand, molecules containing hydrazide (-CO-NH-) skeletons exhibit biological activities such as sterilization, disinsection, and weeding.

The subject combines a 1, 3, 4-oxadiazole structure with a hydrazide substructure, which has a wide range of biological activities, to prepare a 1, 3, 4-oxadiazole hydrazide derivative, from which a compound having a higher biological activity is expected to be found.

The research on the biological activity of hydrazide compounds progresses as follows:

a series of novel fatty hydrazide Derivatives were synthesized in Kostecka et al [ Kostecka, M.Synthesis of aNew Group of Aliphatic hydrazide Derivatives and the correlation between the Molecular structure and Biological activity, molecules, 2012, 17, 3560-3573 ]. The compounds show certain inhibitory activity on poplar fusarium wilt bacteria and pepper fusarium wilt bacteria.

Backes et al [ Backes, g.l.; neumann, d.m.; a series of compounds containing an acyl hydrazine structure are synthesized by Jurisic, B.S. Synthesis and antibacterial activity of substitated salicylic acid, hydrazides and sulfo hydrazides.bioorgan.Med.Chem.2014, 22, 4629-containing 4636, and the results of bioactivity tests show that the target compounds have stronger antibacterial activity on Candida albicans and Candida glabrata.

Wang et al [ Wang, x.; dai, z.c.; chen, y.f.; cao, l.l.; yan, w.; li, s.k.; wang, j.x.; zhang, z.g.; ye, Y.H., Synthesis of 1, 2, 3-triazole hydrazides inhibiting i-phytopathogenic activity.Eur.J.Med.chem.2017, 126, 171-182] reports a series of 1, 2, 3-triazole hydrazide compounds, and biological activity test results show that part of target compounds show better inhibitory activity to phytopathogenic fungi.

The research on the biological activity of the derivatives containing 1, 3, 4-oxadiazole group has progressed as follows:

2014, Shelke et al [ Shelke, s.h.; mhask, p.c.; kasam, s.k.; a Series of derivatives of 2, 5-disubstituted-1, 3, 4-oxadiazoles were designed and synthesized by Bobade, V.D.Synthesis and pharmaceutical Evaluation of a Novel Series of 2- ((2-arylthiozol-4-yl) methyl) -5- (alkyl/alkyl nitrile thio) -1, 3, 4-oxadiazole derivative powders [ J ]. J.heterocyclic Chem.2014, 51, 1893-1897 ]. Biological activity test results show that part of the compounds show better antibacterial activity on aspergillus flavus (A. flavu), the Minimum Inhibitory Concentration (MIC) is 3.125 mu g/mL, and the activity is equivalent to that of a control drug Fluconazole (Fluconazole) (3.125 mu g/mL).

In 2015, Jian et al [ Jian, w.; he, d.; xi, p.; a series of 2, 5-disubstituted-1, 3, 4-oxadiazole derivatives were reported and tested for biological activity by Li, X.Synthesis and biological evaluation of novel fluorine-containing stilbene derivatives as a novel biological agents against a biological activity of a fungal fusion of J.J.Agric.food chem.2015, 63, 9963-9968. The result shows that part of the compounds have good inhibition rate on cucumber colletotrichum.

2017, Wang et al [ Wang, P.Y.; shao, w.b.; xue, h.t.; fang, h.s.; zhou, j.; wu, z.b.; song, b.a.; yang, S.Synthesis of novel 1, 3, 4-oxoderivative diamines as formulating antibiotics and antiviral agents [ J].Res.Chem.Intermediat.，2017，43，6115-6130]A series of 1, 3, 4-oxadiazole derivatives are designed and synthesized, and the biological activity of the derivatives is researched. The results show that part of the compounds have better activity against citrus canker pathogen (Xac), wherein EC₅₀The minimum is 5.9 +/-0.1 mu g/mL, which is superior to the control drug of thiediazole copper (EC)₅₀＝77.0±2.0μg/mL)。

Disclosure of Invention

The invention provides a 1, 3, 4-oxadiazole hydrazide compound or a stereoisomer thereof, or a salt or a solvate thereof.

Another object of the present invention is to provide an intermediate compound for preparing the above compound or its stereoisomer, or its salt or its solvate, and a preparation method thereof.

It is still another object of the present invention to provide a composition comprising the above compound or a stereoisomer thereof, or a salt or solvate thereof.

It is a further object of the present invention to provide the above compounds or stereoisomers thereof, or salts or solvates thereof, or the use of said compositions.

Another object of the present invention is to provide a method for controlling agricultural pests using the above compound or a stereoisomer thereof, or a salt or solvate thereof, or the composition.

In order to realize the purpose, the invention adopts the following technical scheme:

the invention is realized by the following steps: a2, 5-disubstituted-1, 3, 4-oxadiazole-containing hydrazide compound has a structure shown as a general formula (I):

wherein R is₁Independently selected from one or more of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, hydroxy, amino, halogen, mercapto, phosphino, nitro, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl;

R₂independently selected from the group consisting of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl;

preferably, R₁Independently selected from one or more of hydrogen, deuterium, alkyl, alkoxy, hydroxyl, amino, nitro, halogen, mercapto, phosphino, aryl or heteroaryl; preferably, R₁Independently selected from hydrogen, deuterium, C₁-C₆Alkyl radical, C₁-C₆Alkoxy, hydroxy, amino, nitro, halogen, mercapto, phosphino, C₆-C₁₀Aryl or C₅-C₁₀One or more of heteroaryl; more preferably, R₁Independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, hydroxyl, amino, nitro, F, Cl, Br, phenyl, benzyl, pyridyl, furyl, thienyl, chlorophenyl, fluorophenyl, bromophenyl, methoxyphenyl, methylphenyl, ethylphenyl, 1, 2-dichlorophenyl, 1, 3_-One or more of dichlorophenyl, 1, 4-dichlorophenyl, 1, 2-dibromophenyl, 1, 3-dibromophenyl, 1, 4-dibromophenyl, 1, 2-difluorophenyl, 1, 3-difluorophenyl, 1, 4-difluorophenyl; most preferably, R₁Independently selected from hydrogen, deuterium, methyl, ethylOne or more of a group, n-propyl, isopropyl, hydroxyl, amino, nitro, F, Cl, Br, phenyl, furyl, thienyl, chlorophenyl, fluorophenyl, bromophenyl, methoxyphenyl, methylphenyl, ethylphenyl, 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, 1, 4-dicloryl, 1, 2-dibromophenyl, 1, 3-dibromophenyl, 1, 4-dibromophenyl, 1, 2-difluorophenyl, 1, 3-difluorophenyl, 1, 4-difluorophenyl;

preferably, R₂Independently selected from one or more of hydrogen, deuterium, alkyl, alkoxy, cycloalkyl, amino, aryl or heteroaryl; preferably, R₂Independently selected from hydrogen, deuterium, C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₃-C₈Cycloalkyl, amino, C₆-C₁₀Aryl or C₅-C₁₀One or more of heteroaryl; more preferably, R2 is independently selected from the group consisting of hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, pyridyl, furanyl, thienyl, chlorophenyl, fluorophenyl, bromophenyl, methoxyphenyl, methylphenyl, ethylphenyl, trifluoromethylphenyl, nitrophenyl, 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, 1, 4-diclorophenyl, 1, 2-dibromophenyl, 1, 3-dibromophenyl, 1, 4-dibromophenyl, 1, 2-difluorophenyl, 1, 3-difluorophenyl, 2-difluorophenyl, 1, 4-difluorophenyl, 1, 2-dimethylphenyl, 1, 3-dimethylphenyl, 1, 4-dimethylphenyl, 1, 2, 4, 5-tetrafluorophenyl, 1, 2, 3, 4-tetrafluorophenyl, 1, 2, 3, 5-tetrafluorophenyl, 1, 2, 4, 5-dibromophenyl, 1, 2, 3, 4-dibromophenyl, 1, 2, 3, 5-tetrachlorophenyl, 1, 2, 4, 5-tetrachlorophenyl, 1, 2, 3, 4-tetrachlorophenyl, 1, 2, 3, 5-tetrachlorophenyl; most preferably, R₂Independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, cyclopentyl, cycloHexyl, phenyl, benzyl, pyridyl, furyl, thienyl, chlorophenyl, fluorophenyl, bromophenyl, methoxyphenyl, methylphenyl, ethylphenyl, trifluoromethylphenyl, nitrophenyl, 1, 2-dichlorophenyl, 1, 3-dichlorophenyl, 1, 4-dichlorophenyl, 1, 2-dibromophenyl, 1, 3-dibromophenyl, 1, 4-dibromophenyl, 1, 2-difluorophenyl, 1, 3-difluorophenyl, 1, 4-difluorophenyl, 1, 2-dimethylphenyl, 1, 3-dimethylphenyl, 1, 4-dimethylphenyl, 1, 2, 4, 5-tetrafluorophenyl, 1, 2, 3, 4-tetrafluorophenyl, 1, 2, 3, 5-tetrafluorophenyl, 1, 2, 4, 5-dibromophenyl, methoxyphenyl, ethylphenyl, trifluoromethylphenyl, and the like, 1, 2, 3, 4-tetrabromobenzene, 1, 2, 3, 5-tetrabromophenyl, 1, 2, 4, 5-tetrachlorophenyl, 1, 2, 3, 4-tetrachlorophenyl, 1, 2, 3, 5-tetrachlorophenyl.

The preparation method of the 2, 5-disubstituted-1, 3, 4-oxadiazole hydrazide compound is shown as follows:

R₁and R₂As described above.

The 1, 3, 4-oxadiazole hydrazide compound is applied to preparing medicines for resisting plant pathogenic bacteria, fungi and oomycetes.

By adopting the technical scheme, the invention takes 1, 3, 4-oxadiazole methyl formate compounds containing different substituents as the basis, introduces hydrazide capable of improving the bioactivity of a target compound into the system, synthesizes a series of 1, 3, 4-oxadiazole hydrazide compounds, and finds that the compounds have good inhibition effect on pathogenic bacteria and fungi, and have good inhibition effect on pathogenic bacteria [ such as Xanthomonas oryzae pv. oryzae, Xoo ] and plant pathogenic fungi [ Gibberella zeae, G.z ], Fusarium oxysporum, F.o ], blueberry root rot fungi (Phytophora cinmamomi, P.c), Sclerotiopsis sclerotiorum (Sclerotiotiotiotiotiotiotiopsis, S.s), Colletotrichum anthracis (Colletotrichum, nusum, potato C.h) and Phytophora solanum solani, P.i. solani), provides important scientific basis for the research and development of new pesticides.

Preferably, the 1, 3, 4-oxadiazole hydrazide compound of the invention is selected from the following compounds:

an intermediate compound for preparing the compound or a stereoisomer thereof, or a salt or solvate thereof, as shown below:

wherein R is₁As described above.

A process for preparing the compound or a stereoisomer thereof, or a salt or solvate thereof, comprising: compound (I)A step of producing a compound represented by the general formula (I) in the presence of a halogen compound.

The preparation method also comprises the following specific steps:

wherein R is₁And R₂As described above.

The term "alkyl" as used herein is intended to include both branched and straight chain saturated hydrocarbon radicals having the specified number of carbon atoms. E.g. "C_1-10Alkyl "(or alkylene) groups are intended to be C1, C2, C3, C4, C5, C6, C7, C8, C9 and C10 alkyl groups. In addition, for example "C_1-6Alkyl "denotes an alkyl group having 1 to 6 carbon atoms. Alkyl groups may be unsubstituted or substituted such that one or more of its hydrogen atoms are replaced with another chemical group. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, tert-butyl), pentyl (e.g., n-pentyl,isopentyl, neopentyl) and analogs thereof.

"alkenyl" is a hydrocarbon group that includes both straight and branched chain structures and has one or more carbon-carbon double bonds that occur at any stable point in the chain. E.g. "C_2-6Alkenyl "(or alkenylene) is intended to include C2, C3, C4, C5, and C6 alkenyl. Examples of alkenyl groups include, but are not limited to, ethenyl, 1-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl, and the like.

"alkynyl" is intended to include both straight and branched chain hydrocarbons having one or more carbon-carbon triple bonds at any stable point in the chain. E.g. "C_2-6Alkynyl "(or alkynylene) is intended to include C2, C3, C4, C5, and C6 alkynyl; such as ethynyl, propynyl, butynyl, pentynyl, hexynyl and the like.

The term "substituted" as used herein means that any one or more hydrogen atoms on the designated atom or group is replaced with the designated group of choice, provided that the designated atom's generalized valency is not exceeded. If not otherwise stated, substituents are named to the central structure. For example, it is understood that when (cycloalkyl) alkyl is a possible substituent, the point of attachment of the substituent to the central structure is in the alkyl moiety. As used herein, a cyclic double bond is a double bond formed between two adjacent ring atoms (e.g., C ═ C, C ═ N or N ═ N).

Combinations of substituents and or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates. A stable compound or stable structure implies that the compound is sufficiently stable to be isolated in useful purity from the reaction mixture and subsequently formulated to form an effective therapeutic agent. Preferably, the compounds described so far do not contain N-halogen, S (O)₂H or S (O) H group.

The term "cycloalkyl" refers to cycloalkyl groups, including mono-, bi-or polycyclic ring systems. C_3-7Cycloalkyl groups are intended to include C3, C4, C5, C6 and C7 cycloalkyl groups. Examples of cycloalkyl groups include, but are not limited toCyclopropyl, also butyl, cyclopentyl, cyclohexyl, norbornyl and the like. As used herein, "carbocycle" or "carbocycle residue" refers to any stable 3, 4, 5, 6 or 7-membered monocyclic or bicyclic or 7, 8, 9, 10, 11, 12 or 13-membered bi-or tricyclic ring which may be saturated, partially unsaturated, unsaturated or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, pentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadiene, [3.3.0]Bicyclo-octane, [4.3.0]Bicyclo nonane, [4.4.0]Bicyclo decane, [2.2.2]Bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, anthracenyl and tetrahydronaphthyl (tetralin). As mentioned above, bridged rings are also included in carbocyclic rings (e.g. [2.2.2 ]]Bicyclo octane) in the definition of. Preferred carbocycles, if not otherwise stated, are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and phenyl. When the term "carbocycle" is used, it is intended to include "aryl". A bridged ring occurs when one or more carbon atoms connects two non-adjacent carbon atoms. Preferred bridges are one or two carbon atoms. It is pointed out that the bridge always converts a single ring into a double ring. When the rings are bridged, substituents of the rings are also present on the bridge.

The term "aryl" refers to monocyclic or bicyclic aromatic hydrocarbon groups having 6 to 12 carbon atoms in the ring portion, such as phenyl and naphthyl, each of which may be substituted.

The term "halogen" or "halogen atom" refers to chlorine, bromine, fluorine and iodine.

The term "heteroaryl" refers to substituted and unsubstituted aromatic 5 or 6 membered monocyclic groups, 9-or 10-membered bicyclic groups, and 11 to 14 membered tricyclic groups having at least one heteroatom (O, S or N) in at least one ring, said heteroatom containing ring preferably having 1, 2 or 3 heteroatoms selected from O, S and N. The heteroatom-containing heteroaryl groups can contain one or two oxygen or sulfur atoms per ring and/or from 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. The nitrogen and sulfur atoms may optionally be oxidized and the nitrogen atoms may optionally be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one fully aromatic ring, and the other fused rings may be aromatic or non-aromatic. The heteroaryl group may be attached at any available nitrogen or carbon atom of any ring. If the other ring is cycloalkyl or heterocyclic, it is additionally optionally substituted with ═ O (oxygen), as valency permits.

Exemplary monocyclic heteroaryl groups include pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furanyl, thienyl, oxadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, and the like.

Exemplary bicyclic heteroaryls include indolyl, benzothiazolyl, benzodioxolyl, benzoxazolyl, benzothienyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, indolizinyl, benzofuranyl, chromonyl, coumarinyl, benzofuranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, fluoropyridinyl, dihydroisoindolyl, tetrahydroquinolinyl, and the like.

The compounds of the invention are understood to include both the free form and salts thereof, unless otherwise indicated. The term "salt" denotes an acid and/or base salt formed from an inorganic and/or organic acid and a base. In addition, the term "salt" may include zwitterions (internal salts), such as when the compound of formula I contains a basic moiety, such as an amine or pyridine or imidazole ring, and an acidic moiety, such as a carboxylic acid. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, wherein the cation does not contribute significantly to the toxicity or biological activity of the salt. However, other salts may be useful, such as separation or purification steps in the preparation process, and are therefore included within the scope of the present invention. Salts of the compounds of formula I may be formed, for example, by combining a compound of formula I with an amount of acid or base, for example, in equal amounts, in a vehicle, for example, in an aqueous vehicle, in which the salt may precipitate, or in which it is in aqueous form, and then lyophilizing.

By adopting the technical scheme, the invention takes the 1, 3, 4-oxadiazole compound as the basis, introduces hydrazide capable of improving the biological activity of a target compound into the system, synthesizes a series of 1, 3, 4-oxadiazole formylhydrazine compounds, finds that the compounds have good inhibition effect on pathogenic bacteria, fungi and oomycetes, and provides an important scientific basis for the research and development of new pesticides.

Examples

The invention is further illustrated by the following examples. It should be understood that the method described in the examples is only for illustrating the present invention and not for limiting the present invention, and that the simple modification of the preparation method of the present invention based on the concept of the present invention is within the scope of the claimed invention. All the starting materials and solvents used in the examples are commercially available products.