US 11,478,461 B2Granted

[1.1.1] bicyclo compounds as indoleamine 2,3-dioxygenase inhibitors

AssigneeMerck Sharp & Dohme Corp.

InventorsLiangqin Guo, Hongjun Zhang, Ping Chen, Dane Clausen, Xavier Fradera, Yongxin Han, Shuwen He, Xianhai Huang, Alexander Pasternak, Qinglin Pu, Li Xiao, Feng Ye

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Abstract

Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: (I). Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.

Claims19

Dependent claims

A compound of formula (I), or a pharmaceutically acceptable salt thereof:

wherein:
m is 1;
V is selected from
X is selected from a bond, O and N(Ra);
where Ra is selected from hydrogen and C1-6 alkyl;
each occurrence of R1 and R2 is independently selected from:
(i) hydrogen,
(ii) C1-6 alkyl, and
(iii) C3-6 cycloalkyl;
or alternatively, le and R2 together with the carbon to which they are attached form a C3-6 cycloalkyl or a 4-6 membered heterocyclyl;
wherein the C3-6 cycloalkyl is optionally substituted with C1-6 alkyl;
and
each occurrence of R3 and R4 is independently selected from:
(i) C1-6 alkyl, optionally substituted with one to four substituents independently selected from halogen and phenyl,
(ii) C3-6 cycloalkyl,
(iii) aryl, and
(iv) heterocyclyl;
wherein each of the phenyl of (i), aryl of (iii) and heterocyclyl of (iv) is optionally substituted with one to four substituents independently selected from:
(a) halogen,
(b) C1-6 alkyl, optionally substituted with one to four halogens,
(c) —O—C1-6 alkyl, optionally substituted with one to four halogens,
(d) C3-6 cycloalkyl, optionally substituted with one to four halogens, and
(e) —CN.

20 more elements

A compound selected from:

3-chloro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3-chloro-N-(3-(1-((4-fluorophenyl) carbamoyl) cyclobutyl) bicyclo [1.1.1] pentan-1-yl) benzamide,
3-cyano-N-(3-(1-((4-fluorophenyl)carbamoyl)cyclobutyl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3,4-dichloro-N-(3-(1-((4-fluorophenyl)carbamoyl)cyclobutyl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3-chloro-N-(3-(1-((4-chlorophenyl)amino)-1-oxopropan-2-yl)bicyclo [1.1.1] pentan-1-yl) benzamide,
3,4-dichloro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3-chloro-N-(3-(1-((4-chloro-3-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
N-(3-(1-((4-chlorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-3-cyanobenzamide,
3,4-dichloro-N-(3-(1-((6-fluoropyridin-3-yl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3-chloro-N-(3-(1-((6-chloropyridin-3-yl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
N-(3-(1-((6-chloropyridin-3-yl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)bicyclo[4.2.0]octa-1(6),2,4-triene-3-carboxamide,
cyclopropyl (3-(1-((4-chlorophenyl)amino)-1-oxopropan-2-yl)bicyclo [1.1.1] pentan-1-yl) carbamate,
3, 4-dichloro-N-(3-(1-(4-fluorobenzamido)ethyl) bicyclo [1.1.1] pentan-1-yl) benzamide, benzyl (3-(1-(4-fluorobenzamido)cyclopropyl)bicyclo[1.1.1]pentan-1-yl)carbamate,
3,4-dichloro-N-(3-(1-(4-fluorobenzamido)cyclopropyl)bicyclo[1.1.1]pentan-1-yl)benzamide,
5-chloro-N-(3-(1-(4-fluorobenzamido)cyclopropyl)bicyclo[1.1.1]pentan-1-yl)pi colinamide,
N-(3-(1-(4-fluorobenzamido)cyclopropyl)bicyclo[1.1.1]pentan-1-yl)-5-(trifluoromethyl)picolinamide,
4-(difluoromethyl)-N-(3-(1-(4-fluorobenzamido)cyclopropyl)bicyclo[1.1.1]pen tan-1-yl)picolinamide,
N-(3-(1-(4-fluorobenzamido)cyclopropyl)bicyclo[1.1.1]pentan-1-yl)-3-methyl-1,2,4-oxadiazole-5-carboxamide,
3-cyclopropyl-N-(3-(1-(4-fluorobenzamido)cyclopropyl)bicyclo[1.1.1]pentan-1-yl)-1,2,4-oxadiazole-5-carboxamide,
N-(3-(1-(4-fluorobenzamido)cyclopropyl)bicyclo[1.1.1]pentan-1-yl)-5-methyl-1,2,4-oxadiazole-3-carboxamide,
tert-butyl (R)-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)carbamate,
tert-butyl (S)-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)carbamate,
(R)-6-chloro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)picolinamide,
(S)-6-chloro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)picolinamide,
3-chloro-4-fluoro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
3-chloro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-4-methyl-benzamide,
4-chloro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-methyl-benzamide,
3-chloro-2-fluoro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
4-fluoro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-methyl-benzamide,
3-chloro-5-fluoro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
3-fluoro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-4-methyl-benzamide,
N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-(trifluoromethyl)benzamide,
3,4-difluoro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
3-chloro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-4-methyl-benzamide,
4-chloro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-methyl-benzamide,
4-fluoro-N-[3-[(1R)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-methyl-benzamide,
4-chloro-3-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
3-chloro-4-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
3-chloro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-4-methyl-benzamide,
4-chloro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-methyl-benzamide,
3-chloro-2-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
4-chloro-2-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
3-chloro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-2-methyl-benzamide,
4-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-methyl-benzamide,
3-chloro-5-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
5-chloro-2-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-4-methyl-pyrimidin-1-ium-2-carboxamide,
3-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-4-methyl-benzamide,
5-chloro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-3-carboxamide,
6-chloro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-3-carboxamide,
6-chloro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-5-methyl-pyridin-1-ium-2-carboxamide,
N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-(trifluoromethyl)benzamide,
5,6-dichloro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-3-carboxamide,
N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-5,6-dimethyl-pyridin-1-ium-2-carboxamide,
5-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-6-methyl-pyridin-1-ium-3-carboxamide,
N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-2-(trifluoromethyl)pyridin-1-ium-4-carboxamide,
4-fluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-methoxy-benzamide,
N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-5-(trifluoromethyl)pyridin-1-ium-3-carboxamide,
3,4-difluoro-N-[3-[(1S)-2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]benzamide,
(S)—N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-2-naphthamide,
(S)-5,6-dichloro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)picolinamide,
(S)—N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-6-(trifluoromethyl)picolinamide,
(S)-3-chloro-4-cyano-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)-4-cyano-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-3-methylbenzamide,
(S)—N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)quinoline-7-carboxamide,
(S)—N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-6-(trifluoromethyl)nicotinamide,
cyclopentyl (S)-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)carbamate,
benzyl (S)-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)carbamate,
isopropyl (S)-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)carbamate,
cyclopropyl (S)-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)carbamate,
(S)-2-(3-(3-(3-chlorophenyl)ureido)bicyclo[1.1.1]pentan-1-yl)-N-(4-fluorophenyl)propanamide,
(S)-2-(3-(3-(3,4-difluorophenyl)ureido)bicyclo[1.1.1]pentan-1-yl)-N-(4-fluorophenyl)propanamide,
(S)-2-(3-(3-(3-chloro-4-fluorophenyl)ureido)bicyclo[1.1.1]pentan-1-yl)-N-(4-fluorophenyl)propanamide,
(S)-2-(3-(3-(3-chloro-2-methylphenyl)ureido)bicyclo[1.1.1]pentan-1-yl)-N-(4-fluorophenyl)propanamide,
(S)—N-(4-fluorophenyl)-2-(3-(3-(4-fluorophenyl)ureido)bicyclo[1.1.1]pentan-1-yl)propanamide,
(S)—N-(4-fluorophenyl)-2-(3-(3-(naphthalen-1-yl)ureido)bicyclo[1.1.1]pentan-1-yl)propanamide,
(S)—N-(4-fluorophenyl)-2-(3-(3-(3-(trifluoromethyl)phenyl)ureido)bicyclo[1.1.1]pentan-1-yl)propanamide,
(R)-3,4-dichloro-N-(3-(1-((5,6-difluoropyridin-3-yl)amino)-1-oxopropan-2-yl) bicyclo[1.1.1]pentan-1-yl)benzamide,
(R)-3,4-dichloro-N-(3-(1-((6-chloro-5-fluoropyridin-3-yl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(R)-3,4-dichloro-N-(3-(1-((2-chloropyrimidin-5-yl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(R)-3,4-dichloro-N-(3-(1-((3,4-difluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(R)-3,4-dichloro-N-(3-(1-oxo-1-((4-(trifluoromethyl)phenyl)amino)propan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)-3,4-dichloro-N-(3-(1-((5,6-dichloropyridin-3-yl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)-3-chloro-5-(2-(3-(3,4-dichlorobenzamido)bicyclo[1.1.1]pentan-1-yl)propanamido)pyridin-1-ium,
(S)-3,4-dichloro-N-(3-(1-((4-fluoro-3-(trifluoromethyl)phenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)-3,4-dichloro-N-(3-(1-((3-chloro-4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)-3,4-dichloro-N-(3-(1-((3,4-difluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)-3,4-dichloro-N-(3-(1-oxo-1-((4-(trifluoromethyl)phenyl)amino)propan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)-3,4-dichloro-N-(3-(1-oxo-1-((3-(trifluoromethyl)phenyl)amino)propan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3,4-dichloro-N-(3-(1-((4-fluorophenyl)carbamoyl)cyclopropyl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3,4-dichloro-N-(3-(1-((4-fluorophenyl)amino)-2-methyl-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3-chloro-N-(3-(1-((4-fluorophenyl)amino)-2-methyl-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3,4-dichloro-N-(3-(2-(4-fluorobenzamido)propan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
3-(3-(3-chlorobenzamido)bicyclo[1.1.1]pentan-1-yl)-N-(4-fluorophenyl)oxetane-3-carboxamide,
3-(3-(3-chlorobenzamido)bicyclo[1.1.1]pentan-1-yl)-N-(3,4-difluorophenyl)oxetane-3-carboxamide,
3-(3-(3,4-difluorobenzamido)bicyclo[1.1.1]pentan-1-yl)-N-(4-fluorophenyl)oxetane-3-carboxamide,
3-(3-(3,4-difluorobenzamido)bicyclo[1.1.1]pentan-1-yl)-N-(3,4-difluorophenyl)oxetane-3-carboxamide,
N-(4-chlorophenyl)-3-(3-(3,4-difluorobenzamido)bicyclo[1.1.1]pentan-1-yl)oxetane-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-(trifluoromethoxy)benzamide,
5-ethyl-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]isoxazole-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]imidazo[1,5-a]pyridin-2-ium-5-carboxamide,
4-chloro-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-2-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyrazolo[1,5-a]pyridin-1-ium-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-3-methyl-1,2,4-oxadiazole-5-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-4,5,6,7-tetrahydro-1,2-benzoxazole-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]indolizine-2-carboxamide,
4-ethyl-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-2-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-4-methyl-pyridin-1-ium-2-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-6-methyl-pyridin-1-ium-2-carboxamide,
5-cyclopropyl-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]isoxazole-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-2-oxo-indoline-4-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-5-methyl-pyridin-1-ium-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-2-methyl-thiazole-4-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-5-methyl-pyrazolo[1,5-a]pyridin-1-ium-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-2-methoxy-pyridin-1-ium-4-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyrazolo[1,5-a]pyridin-1-ium-7-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]indolizine-1-carboxamide,
N-(4-fluorophenyl)-2-[3-[[2-[2-(trifluoromethyl)phenyl]acetyl]amino]-1-bicyclo[1.1.1]pentanyl]propanamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-2-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]isoquinolin-2-ium-8-carboxamide,
1-(difluoromethyl)-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyrazole-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-6-methyl-pyridin-1-ium-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-5-(trifluoromethyl)pyridin-1-ium-2-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]isoquinolin-2-ium-5-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]cinnoline-4-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-2,4-dimethyl-thiazole-5-carboxamide,
3-fluoro-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-2-carboxamide,
6-ethoxy-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-2-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-2,5-dimethyl-pyrazole-3-carboxamide,
5-chloro-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyrazine-2-carboxamide,
5-ethyl-N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]-2-methyl-pyrazole-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]pyridin-1-ium-3-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]triazolo[1,5-a]pyridin-1-ium-4-carboxamide,
N-[3-[2-(4-fluoroanilino)-1-methyl-2-oxo-ethyl]-1-bicyclo[1.1.1]pentanyl]isoquinolin-2-ium-3-carboxamide,
(S)-3,4,5-trifluoro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)—N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-6-(trifluoromethyl)nicotinamide,
(S)—N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)quinoline-7-carboxamide,
(S)—N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-2-naphthamide,
(S)-5,6-dichloro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)picolinamide,
(S)-3-chloro-4-cyano-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide,
(S)-4-cyano-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-3-methylbenzamide,
(S)—N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-6-(trifluoromethyl)picolinamide,
(S)-3,5-difluoro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide, and
(S)-2,4,5-trifluoro-N-(3-(1-((4-fluorophenyl)amino)-1-oxopropan-2-yl)bicyclo[1.1.1]pentan-1-yl)benzamide;
or a pharmaceutically acceptable salt thereof.

142 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/047,247Filed 15 Apr 2019 · us provisional application
Priority: 19 Apr 2018
Published: US 2021/0393600 A123 Dec 2021
Granted: 25 Oct 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification52 codes

A61K 31/44
Having six-membered rings with one nitrogen as the only ring hetero atom: non condensed pyridines; Hydrogenated derivatives thereof
A61K 31/167
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the nitrogen of a carboxamide group directly attached to the aromatic ring,…
A61K 31/17
Amides, e.g. hydroxamic acids: having the group >N—C—N< or >N—C—N<, e.g. urea, thiourea, carmustine
A61K 31/27
Esters, e.g. nitroglycerine, selenocyanates: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine