Oximido naphthoquinone compound and preparation method and application thereof
阅读说明：本技术 肟基萘醌类化合物及其制备方法和用途 (Oximido naphthoquinone compound and preparation method and application thereof ) 是由 王恒山 经孝腾 黄日镇 贾强 褚长虎 吕玉泉 于 2019-07-11 设计创作，主要内容包括：本申请属于药物化合物和药物技术领域,涉及肟基萘醌类化合物及其制备方法和用途,具体涉及式(I)的化合物,该化合物能够作为STAT3和IDO1的双靶点选择性抑制剂,其用于治疗卵巢癌、结肠癌及肺癌等(The present application pertains to pharmaceutical compoundsAnd the technical field of medicaments, relates to oximido naphthoquinone compounds, a preparation method and application thereof, and particularly relates to a compound shown in a formula (I), wherein the compound can be used as a double-target selective inhibitor of STAT3 and IDO1 and is used for treating ovarian cancer, colon cancer, lung cancer and the like)
A compound of formula (I):
wherein
X is C optionally substituted with one or more groups selected from6-C 10Aryl or 5-to 10-membered heteroaryl: halogen, hydroxy, mercapto, optionally substituted hydrocarbylthio, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group;
each R is1Independently selected from hydrogen, halogen, hydroxyl, mercapto, optionally substituted hydrocarbon sulfenyl and optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group;
n is an integer selected from 1,2,3, 4 or 5;
each R is2Independently selected from hydrogen, halogen, hydroxyl, mercapto, optionally substituted hydrocarbon sulfenyl and optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, optionallySubstituted halogeno C1-C 6Alkoxy, sulfinyl, sulfonyl, S-sulfonylamino, N-sulfonylamino, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, and N-acylamino;
m is an integer selected from 1,2,3 or 4; and
R 3selected from hydrogen, halogen, hydroxy, mercapto, optionally substituted hydrocarbylthio, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkoxy, sulfinyl, sulfonyl, S-sulfonylamino, N-sulfonylamino, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, and N-acylamino;
or a pharmaceutically acceptable salt thereof.
The compound of claim 1, wherein said C is6-C 10Aryl is phenyl.
The compound of claim 1, wherein the 5-to 10-membered heteroaryl is pyridyl or thienyl.
The compound of claim 1, wherein said C is6-C 10Aryl is optionally substituted with a group selected from: halogen, hydroxy, mercapto, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxyC 1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group.
The compound of claim 1, wherein said C is6-C 10Aryl is phenyl, optionally substituted with a group selected from: halogen, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkoxy, and optionally substituted halogeno C1-C 6An alkyl group.
The compound of claim 1, wherein each R is1Are all hydrogen.
The compound of claim 1, wherein each R is2Are all hydrogen.
The compound of claim 1, wherein R is3Is hydrogen.
A compound selected from:
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4- (trifluoromethyl) phenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-fluorophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3, N-diphenyl-propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-fluorophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-methoxyphenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3, 5-dimethylphenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-chlorophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-bromophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-bromo-4-fluorophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3- (trifluoromethyl) phenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-fluorophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-tolyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-chlorophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-chlorophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-bromophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-bromophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-methoxyphenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-methoxyphenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-tolyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3, 5-dimethoxyphenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-fluoro-4-bromophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3, 5-difluorophenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-fluoro-4-methylphenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2, 5-dimethoxyphenyl) -propionamide;
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-chloro-4-methylphenyl) -propionamide; and
(R) -2- ((4- (hydroxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-methyl-4-bromophenyl) -propionamide;
or a pharmaceutically acceptable salt thereof.
A compound of formula (II):
wherein
X is C optionally substituted with one or more groups selected from6-C 10Aryl or 5-to 10-membered heteroaryl: halogen, hydroxy, mercapto, optionally substituted hydrocarbylthio, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group;
each R is1Independently selected from hydrogen, halogen, hydroxyl, mercapto, optionally substituted hydrocarbon sulfenyl and optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group;
n is an integer selected from 1,2,3, 4 or 5;
each R is2Independently selected from hydrogen, halogen, hydroxyl, mercapto, optionally substituted hydrocarbon sulfenyl and optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkoxy, sulfinyl, sulfonyl, S-sulfonylamino, N-sulfonylamino, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, and N-acylamino;
m is an integer selected from 1,2,3 or 4; and
R 3selected from hydrogen, halogen, hydroxy, mercapto, optionally substituted hydrocarbylthio, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkoxy, sulfinyl, sulfonyl, S-sulfonylamino, N-sulfonylamino, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, and N-acylamino;
or a pharmaceutically acceptable salt thereof.
The compound of claim 10, wherein C is6-C 10Aryl is phenyl.
The compound of claim 10, wherein the 5-to 10-membered heteroaryl is pyridyl or thienyl.
The compound of claim 10, wherein C is6-C 10Aryl is optionally substituted with a group selected from: halogen, hydroxy, mercapto, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group.
The compound of claim 10, wherein C is6-C 10Aryl is phenyl, optionally substituted with a group selected from: halogen, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkoxy, and optionally substituted halogeno C1-C 6An alkyl group.
The compound of claim 10, wherein each R is1、R 2Are each hydrogen, R3Is hydrogen.
A compound selected from:
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4- (trifluoromethyl) phenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-fluorophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3, N-diphenyl-propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-fluorophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-methoxyphenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3, 5-dimethylphenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-chlorophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-bromophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-bromo-4-fluorophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3- (trifluoromethyl) phenyl) propanamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-fluorophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-tolyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-chlorophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-chlorophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-bromophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-bromophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-methoxyphenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-methoxyphenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (4-tolyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3, 5-dimethoxybenzene;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-fluoro-4-bromophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3, 5-difluorophenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-fluoro-4-methylphenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2, 5-dimethoxyphenyl) -propionamide;
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-chloro-4-methylphenyl) -propionamide; and
(R) -2- ((1, 4-dioxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (2-methyl-4-bromophenyl) -propionamide;
or a pharmaceutically acceptable salt thereof.
A compound of formula (III):
wherein
X is optionally taken by one or more groups selected fromSubstituted C6-C 10Aryl or 5-to 10-membered heteroaryl: halogen, hydroxy, mercapto, optionally substituted hydrocarbylthio, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group;
each R is1Independently selected from hydrogen, halogen, hydroxyl, mercapto, optionally substituted hydrocarbon sulfenyl and optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group;
n is an integer selected from 1,2,3, 4 or 5;
each R is2Independently selected from hydrogen, halogen, hydroxyl, mercapto, optionally substituted hydrocarbon sulfenyl and optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkoxy radicalSulfinyl, sulfonyl, S-sulfonylamino, N-sulfonylamino, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, and N-acylamino;
m is an integer selected from 1,2,3 or 4;
R 3selected from hydrogen, halogen, hydroxy, mercapto, optionally substituted hydrocarbylthio, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkoxy, sulfinyl, sulfonyl, S-sulfonylamino, N-sulfonylamino, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-acylamino, and N-acylamino; and
R 4is C optionally substituted by one or more groups selected from6-C 10Aryl or 5-to 10-membered heteroaryl: halogen, hydroxy, mercapto, optionally substituted hydrocarbylthio, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkenyl, optionally substituted C1-C 6Alkynyl, optionally substituted C1-C 6Alkoxy, optionally substituted amino, optionally substituted hydroxy C1-C 6Alkyl, optionally substituted halogeno C1-C 6Alkyl, and optionally substituted halo C1-C 6An alkoxy group;
or a pharmaceutically acceptable salt thereof.
The compound of claim 17A compound of formula (I), wherein said C6-C 10Aryl is phenyl and the 5-to 10-membered heteroaryl is pyridyl or thienyl.
The compound of claim 17, wherein C is6-C 10Aryl is phenyl, optionally substituted with a group selected from: halogen, optionally substituted C1-C 6Alkyl, optionally substituted C1-C 6Alkoxy, and optionally substituted halogeno C1-C 6An alkyl group.
The compound of claim 17, wherein R is1、R 2Are each hydrogen, R3Is hydrogen.
The compound of claim 17, wherein C is6-C 10Aryl is phenyl and the 5-to 10-membered heteroaryl is thienyl.
A compound selected from:
(R) -2- ((4- ((((4- (tert-butyl) phenyl) sulfonyl) oxy) imino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3- (trifluoromethyl) phenyl) -propionamide;
(R) -2- ((4- ((((4- (tert-butyl) phenyl) sulfonyl) oxy) imino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-bromophenyl) -propionamide; and
(R) -2- ((4- ((((4- (tert-butyl) phenyl) sulfonyl) oxy) imino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenyl-N- (3-methoxyphenyl) -propionamide;
or a pharmaceutically acceptable salt thereof.
A process for preparing a compound according to any one of claims 10 to 16, said process comprising steps a) to e) as shown below:
a) reacting phthalic anhydride with L-phenylalanine, the phenyl group of which is optionally substituted by 1 to n R1Substitution;
b) reacting the product obtained in step a) with C2O 2Cl 2Carrying out reaction;
c) reacting the product obtained in step b) with X-NH2Carrying out reaction;
d) reacting the product obtained in step c) with hydrazine;
e) reacting the product obtained in step d) with 1, 4-naphthoquinone, the phenyl ring of which is optionally substituted by 1 to m R2Substituted and carbon at position 2 optionally substituted with R3(iii) substitution, thereby obtaining a compound of formula (II);
x, R therein1、n、R 2M and R3As claimed in claim 10.
The method of claim 23, wherein:
the reaction conditions of step a) are a reaction in acidic solution at 55-85 ℃, preferably at 70 ℃ for 10-14 hours, preferably 12 hours;
the reaction conditions of step b) are a reaction in a solution of a haloalkane at 0-15 ℃, preferably at 0 ℃, for 10-14 hours, preferably 12 hours;
the reaction conditions of step c) are such that the reaction is carried out in a solution of a haloalkane at 0 to 15 ℃, preferably at 0 ℃, for 20 to 40 minutes, preferably for 30 minutes;
the reaction condition of the step d) is that the reaction is carried out for 2.5 to 3.5 hours in the alcohol solution at room temperature;
the reaction condition of the step e) is that the reaction is carried out for 18 to 24 hours in a mixed solution of triethylamine, N-dimethylformamide and water at room temperature.
A process for the preparation of a compound according to any one of claims 1 to 9, said process comprising step f) as shown below:
the step f) is to react the compound of the formula (II) with hydroxylamine hydrochloride, preferably, the reaction condition of the step f) is to react in alcohol solution at 70-80 ℃ for 10-14 hours, preferably 12 hours, so as to obtain the compound of the formula (I), wherein X, R1、n、R 2M and R3Is as claimed in claim 1.
A process for the preparation of a compound according to any one of claims 17 to 22, comprising step g) as shown below:
the step g) is to react the compound of the formula (I) with ClSO2R 4Reaction, preferably the reaction conditions of step g) are a reaction in dichloromethane at 0-15 ℃, preferably at 0 ℃ for 20-40 minutes, preferably 30 minutes, under an inert gas, followed by dropwise addition of triethylamine and reaction for 10-20 minutes; x, R therein1、n、R 2、m、 R 3And R4As claimed in claim 17.
(R) -N- (3, 5-dimethoxyphenyl) -2- ((4- (methoxyimino) -1-oxo-1, 4-dihydronaphthalen-2-yl) amino) -3-phenylpropanamide or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a compound of any one of claims 1-9, 17-22, or 27, or a pharmaceutically acceptable salt thereof, or a compound prepared by the process of claim 25 or 26, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, excipients, or a combination thereof.
Use of a compound of any one of claims 1-9, 17-22 or 27, or a pharmaceutically acceptable salt thereof, a compound prepared by the process of claim 25 or 26, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 28, for inhibiting STAT3 and/or IDO 1.
Use of a compound of any one of claims 1-9, 17-22 or 27, or a pharmaceutically acceptable salt thereof, a compound prepared by the process of claim 25 or 26, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 28, in the manufacture of a medicament for inhibiting STAT3 and/or IDO 1.
Use of a compound of any one of claims 1-9, 17-22, or 27, or a pharmaceutically acceptable salt thereof, a compound prepared by the process of claim 25 or 26, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 28, in the manufacture of a medicament for the treatment of cancer.
The use of claim 31, wherein the cancer is selected from the group consisting of colon cancer, ovarian cancer, liver cancer, bladder cancer, cervical cancer, and small cell lung cancer.
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