CN-116457355-B - 2-Amino-3-carbonyl imidazopyridines and pyrazolopyridines compounds

CN116457355BCN 116457355 BCN116457355 BCN 116457355BCN-116457355-B

Abstract

The present disclosure provides a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a pharmaceutical composition comprising the same, and a method for treating or preventing inflammatory and autoimmune diseases, particularly neuroinflammatory diseases, using the same.

Inventors

J.LI
M.JIN
I.Yang
S.Zhao
K.Lin
A. Y. Park
Gard Chandev Gorashna
H .nan
Y.Quan
Y.HUANG
J.E.Jin

Assignees

第一生物治疗股份有限公司

Dates

Publication Date: 20260508
Application Date: 20210914
Priority Date: 20200915

Claims (6)

1.A compound of formula (I): Or a pharmaceutically acceptable salt thereof, wherein: R 1 and R 2 are independently-H, C 1 -C 6 alkyl, or C 1 -C 4 alkanoyl, wherein each R 1 and R 2 is optionally substituted with one or more groups selected from methylaminomethyl, and ethylaminomethyl, or R 1 and R 2 together form a 5-membered heterocyclic ring; R 3 is selected from methyl, butyl, methoxy, pyridinyl, phenyl, cyclopropyl, cyclobutyl, pyrazolyl, azetidinyl, pyrimidinyl, pyrrolidinyl, cyclopropylamino, and tetrahydrofuranyl, wherein R 3 is optionally substituted with one or more groups selected from halogen, and C 1 -C 12 alkyl; R 4 and R 5 are independently-H, or halogen; R 6 is selected from bromo, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, pyrrolyl, imidazolyl, triazolyl, tetrazolyl, thienyl, furanyl, oxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyridinyl, imidazopyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl, wherein R 6 is optionally substituted with one or more groups selected from halogen, hydroxy, C 1 -C 12 alkyl, C 1 -C 12 alkenyl, C 1 -C 12 haloalkyl, C 1 -C 10 haloalkoxy, C 1 -C 10 hydroxyalkyl, C 1 -C 10 aminoalkyl, C 1 -C 10 alkylamino, morpholinyl, piperazinyl, and methylpiperazinyl; x is N, and Y is C.
2. A compound according to claim 1, selected from: (2-amino-6- (1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-indol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-indol-6-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-indol-7-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-methyl-1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-8-fluoro-6- (1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-chloro-1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-8-fluoro-6- (1H-indol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-methyl-1H-indol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-fluoro-1H-indol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-chloro-1H-indol-3-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (6-fluoro-1H-indol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (6-fluoro-5-methyl-1H-indol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 r) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 r) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-methyl-1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 r) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-methyl-1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-methyl-1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 r) -2-fluorocyclopropyl) methanone; 3- (2-amino-3- ((1 s,2 s) -2-fluorocyclopropane-1-carbonyl) imidazo [1,2-a ] pyridin-6-yl) -1H-indole-1-carboxylic acid tert-butyl ester; (2-amino-6- (1H-indol-3-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6-bromoimidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (thiophen-2-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2- (trifluoromethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- (trifluoromethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2, 3-dimethylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2, 5-dimethylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2, 4-dimethylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2-fluoro-6-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2-methyl-3- (trifluoromethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2-fluoro-6-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (furan-2-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-methylthiazol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-methylthiophene-2-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (thiazol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3, 4-difluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 r) -2-fluorocyclopropyl) methanone, (2-amino-6- (2-chlorophenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 r) -2-fluorocyclopropyl) methanone; 1- (4- (2-amino-3- ((1 s,2 s) -2-fluorocyclopropane-1-carbonyl) imidazo [1,2-a ] pyridin-6-yl) -3-methylphenyl) ethan-1-one; (2-amino-6- (4-morpholinophenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-methyl-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-chloro-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 r) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2-chloro-3-fluorophenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2-methyl-5- (trifluoromethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (S) - (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (2, 2-difluorocyclopropyl) methanone; (2-amino-6- (4- (piperazin-1-yl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4- (4-methylpiperazin-1-yl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3- (4-methylpiperazin-1-yl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (6-fluoro-5-methyl-1H-indazol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (7- (dimethylamino) -6-fluoro-5-methyl-1H-indazol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (6-fluoro-5-methyl-7- (methylsulfanyl) -1H-indazol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (benzofuran-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-chloro-6-fluoro-1H-indazol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-chloro-7- (dimethylamino) -6-fluoro-1H-indazol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-chloro-6-fluoro-7- (methylsulfanyl) -1H-indazol-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-fluoro-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-methylisothiazol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-indazol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-chloro-1H-indazol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-methyl-1H-indazol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-8-fluoro-6- (4-methyl-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-8-fluoro-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-benzo [ d ] imidazol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-methyl-1H-benzo [ d ] imidazol-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H pyrrolo [2,3-b ] pyridin-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1, 4-dimethyl-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; 2-amino-6- (3-fluoro-2-methylphenyl) -N- ((1 r,2 s) -2-fluorocyclopropyl) imidazo [1,2-a ] pyridine-3-carboxamide; (2-amino-6- (1H pyrrolo [2,3-b ] pyridin-3-yl) imidazo [1,2-a ] pyridin-3-alkyl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (quinolin-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (quinolin-3-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (isoquinolin-4-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2- (2-fluoroethoxy) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone, (2-amino-6- (2- (2-fluoroethoxy) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- (2-fluoroethoxy) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; 2- (2-amino-3- ((1 s,2 s) -2-fluorocyclopropane-1-carbonyl) imidazo [1,2-a ] pyridin-6-yl) -1H-pyrrole-1-carboxylic acid tert-butyl ester; 3- (2-amino-3- ((1 s,2 s) -2-fluorocyclopropane-1-carbonyl) imidazo [1,2-a ] pyridin-6-yl) -1H-pyrrole-1-carboxylic acid tert-butyl ester; (2-amino-6- (3-fluoro-2- (3-hydroxypropyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-pyrrol-2-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (1H-pyrrol-3-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- (2-hydroxyethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- (hydroxymethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2- (2-hydroxyethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2- (3-hydroxypropyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2- (2-fluoroethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- (3-fluoropropyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2- (3-fluoropropyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-amino-5-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (4-amino-2-fluoro-5-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- (2-fluoroethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (tert-butyl 2- (2-amino-3- ((1 s,2 s) -2-fluorocyclopropane-1-carbonyl) imidazo [1,2-a ] pyridin-6-yl) benzyl) carbamate; (2-amino-6- (2- (aminomethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (2- (2-fluoroethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 r) -2-fluorocyclopropyl) methanone; (2-amino-6- (2- (2-fluoroethyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- (2-fluoroethoxy) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 r) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-amino-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- ((E) -2-methoxyvinyl) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2-vinylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-fluoro-2-methyl-3- (methylamino) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3- (dimethylamino) -5-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- ((3-fluoro-2-methylphenyl) amino) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2- (2-fluoroethoxy) phenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 r) -2-fluorocyclopropyl) methanone; (2-amino-6- (5-amino-3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6- (3-fluoro-2-methylphenoxy) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2-amino-6-bromoimidazo [1,2-a ] pyridin-3-yl) (cyclopropyl) methanone; (2-amino-6- (4-methylpyridin-3-yl) imidazo [1,2-a ] pyridin-3-yl ] (cyclopropyl) methanone; (2-amino-6- (5-methyl-1H-indazol-4-yl) imidazo [1,2-a ] pyridin-3-yl) (cyclopropyl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (cyclopropyl) methanone; 1- (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ethan-1-one; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (pyridin-2-yl) methanone, (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (phenyl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (cyclobutyl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (1-methyl-1H-pyrazol-4-yl) methanone; 1- (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) -2, 2-dimethylpropane-1-one; 1- (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) pentan-1-one; Tert-butyl 2- (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridine-3-carbonyl) azetidine-1-carboxylate; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (3, 3-difluorocyclobutyl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (azetidin-2-yl) methanone; 3- (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridine-3-carbonyl) azetidine-1-carboxylic acid tert-butyl ester; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (azetidin-3-yl) methanone; (2-amino-6- (1H-indol-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyridin-2-yl) methanone; (2-amino-6- (1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyridin-2-yl) methanone; (2-amino-6- (4-methyl-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyridin-2-yl) methanone; (2-amino-6- (4-chloro-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyridin-2-yl) methanone; (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (pyrimidin-2-yl) methanone, (2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) (pyrimidin-4-yl) methanone, (2-amino-6- (1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyrimidin-4-yl) methanone; (2-amino-6- (1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyrimidin-2-yl) methanone; (2-amino-6- (4-methyl-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (azetidin-3-yl) methanone; (2-amino-6- (4-chloro-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (azetidin-3-yl) methanone; (2-amino-6- (4-methyl-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyrimidin-4-yl) methanone; (2-amino-6- (4-methyl-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyrimidin-2-yl) methanone; (2-amino-6- (1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (azetidin-3-yl) methanone; (2-amino-6- (1H pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyrrolidin-3-yl) methanone; (2-amino-6- (4-methyl-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyrrolidin-3-yl) methanone; (2-amino-6- (4-chloro-1H-pyrrolo [2,3-b ] pyridin-5-yl) imidazo [1,2-a ] pyridin-3-yl) (pyrrolidin-3-yl) methanone; 2-amino-N-cyclopropyl-6- (3-fluoro-2-methylphenyl) -N-methylimidazo [1,2-a ] pyridine-3-carboxamide; 2-amino-N-cyclopropyl-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridine-3-carboxamide; n' -acetyl-2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridine-3-carbohydrazide; 2-amino-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridine-3-carboxylic acid methyl ester; 2-amino-6- (5-chloro-7- (dimethylamino) -6-fluoro-1H-indazol-4-yl) -N-cyclopropylimidazo [1,2-a ] pyridine-3-carboxamide; (3 s,4 r) -4-methyltetrahydrofuran-3-yl 2-amino-6- (5-chloro-6-fluoro-7- (methylsulfanyl) -1H-indazol-4-yl) imidazo [1,2-a ] pyridine-3-carboxylate; (2- ((2- (dimethylamino) ethyl) amino) -6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2- ((2-aminoethyl) amino) -6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; 6- (3-fluoro-2-methylphenyl) -2- (methylamino) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (2- (dimethylamino) -6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-3-yl) ((1 r,2 s) -2-fluorocyclopropyl) methanone; (6- (3-fluoro-2-methylphenyl) -3- ((1 s,2 s) -2-fluorocyclopropane-1-carbonyl) imidazo [1,2-a ] pyridin-2-yl) carbamic acid tert-butyl ester; (6- (3-fluoro-2-methylphenyl) -2- (pyrrolidin-1-yl) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; (6- (3-fluoro-2-methylphenyl) -2- ((2- (methylamino) ethyl) amino) imidazo [1,2-a ] pyridin-3-yl) ((1 s,2 s) -2-fluorocyclopropyl) methanone; n- (6- (3-fluoro-2-methylphenyl) -3- ((1S, 2S) -2-fluorocyclopropane-1-carbonyl) imidazo [1,2-a ] pyridin-2-yl) acetamide, and N- (3-acetyl-6- (3-fluoro-2-methylphenyl) imidazo [1,2-a ] pyridin-2-yl) acetamide.
3. A compound according to any one of claims 1 or 2, wherein the salt is a hydrochloride, tartrate, phosphate or maleate salt.
4. A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
5. The pharmaceutical composition of claim 4, further comprising one or more active ingredients useful in the treatment of neurodegenerative diseases.
6. Use of a compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to any one of claims 4 to 5, in the manufacture of a medicament for the treatment of a disease associated with RIPK2 and/or c-abl kinase, wherein the disease is an inflammatory or autoimmune disease selected from the group consisting of a-synucleinopathy, parkinson's disease, lewy body dementia, multiple system atrophy, alzheimer's disease, and amyotrophic lateral sclerosis.

Description

2-Amino-3-carbonyl imidazopyridines and pyrazolopyridines compounds Cross Reference to Related Applications The present application claims priority from U.S. provisional patent application No.63/078,372, filed 9/15 in 2020. The entire disclosure of the application identified in this paragraph is incorporated herein by reference. Technical Field The present disclosure relates generally to compounds having enzyme inhibitory activity, pharmaceutical compositions comprising the compounds, and methods of using the compounds to treat diseases. Background Receptor Interacting Protein Kinases (RIPKs) are the Ser/Thr and Tyr kinase families, playing an important role in inflammation and innate immunity. Kinase activity of RIPK1 and RIPK3 has been found to be critical for the activation of necrotic cell death pathways by a variety of stimuli including the tnfα cytokine family, interferon (IFN), and Toll-like receptor (TLR) ligands (Christofferson and Yuan,2010;Vanlangenakker et al, 2012). Importantly, RIPK1/3 kinases are associated with a variety of pathological conditions that currently lack effective therapies, including stroke, myocardial infarction, retinal damage, fatal Systemic Inflammatory Response Syndrome (SIRS) and chronic intestinal and skin inflammation, as well as acute pancreatitis (LINKERMANN AND GREEN, 2014). RIPK2 is another RIP kinase involved in NF- κb activation, mitogen-activated protein kinase (MAPK) and apoptosis. The kinase activity of RIPK2 is essential for signaling through NF- κb and MAPK JNK ('Jun N-terminal kinase'), but is essential for activation of MAPK ERK 2. The most prominent function of RIPK2 is that it mediates signal transduction from NOD ("nucleotide binding oligomerization domain") proteins NOD1 and NOD2, NOD1 and NOD2 being cytosolic pathogen recognition receptors that activate pro-inflammatory and antibacterial responses in response to bacterial peptidoglycans in macrophages. NOD1 and NOD2 are homologous proteins consisting of a caspase recruitment domain (CARD), a nucleotide binding domain, and a leucine rich repeat. Upon recognition of its ligand, NOD1 or NOD2 recruits RIPK2 through CARD-CARD isotype interactions. This process promotes ubiquitination of RIPK2 and activation of the TAK1 and IKK complexes, thereby activating NF- κb and MAPK, and production of pro-inflammatory cytokines by macrophages. RIPK2 also recruits various ubiquitin E3 ligases to the NOD2 complex, including XIAP ("X chromosome-linked apoptosis inhibitor"), cIAP1 and cIAP2, PELL3 and LUBAC. XIAP deficiency has been shown to result in NOD1 or NOD2 mediated ubiquitination of RIPK2 and impairment of inflammatory signaling. XIAP is recruited to the NOD2-RIPK2 complex by binding to the kinase domain of RIPK2, which results in ubiquitination of K63 and LUBAC recruitment of RIPK2, which effectively activates NF- κb and MAPK, and cytokine production in macrophages. The ubiquitination sites of RIPK2 (Lys 209, lys410 and Lys 538) play a critical role in their function of mediating signaling through NOD1 and NOD 2. The D146N kinase inactivating mutant of RIPK2 retains the ability to bind XIAP and activate NOD2 signaling, indicating that kinase activity of RIPK2 is not required for signaling by NOD1 and NOD 2. Such pathology may be caused by positive or negative deregulation of the pathway (Caruso et al, 2014;Jostins et al, 2012;Philpott et al, 2014). Genetic variation in NOD2 is the strongest predisposing factor for crohn's disease (Hugot et al, 2001;Jostins et al, 2012; ogura et al, 2001 a) crohn's disease-related mutations disrupt the binding of NOD2 to MDP, possibly inducing excessive inflammatory signaling from other pattern recognition receptors including NOD1 (Couturier-MAILLARD ET al, 2013;Inohara et al, 2003), in comparison to the mutation of the second major crohn's disease susceptibility factor ATG16L1, thereby increasing the activation of rid 2 (Sorbara et al, 2013) in pediatric also known as inflammatory disorders (tid 2), and in addition to the development of multiple inflammatory disorders in the coronary artery, 20142, 20113) as a key underlying immune system for the treatment of the multiple inflammatory diseases, including the multiple inflammatory diseases of the deep-related to the peripheral nerve system of the human eye, 2011, the multiple inflammatory diseases (13, 20142, 20113) are established as a key underlying immune system of the inflammatory diseases. Alpha-synuclein is part of a large family of proteins, including beta-and gamma-synuclein and synaptoproteins. Alpha-synuclein is expressed in normal states associated with synapses and is thought to play a role in neural plasticity, learning and memory. Several studies have shown that α -synuclein plays an important role in the pathogenesis of parkinson's disease. Molecular changes in alpha-synuclein that increase protein misfolding and aggregation have a direct role in disease pathogenesis. Aggregation of α -synuclein contributes to the f