(1 h-indol-5-yl)acrylamide derivatives as inhibitors of TEAD proteins and the hippo-YAP1/TAZ signaling cascade for the treatment of cancer

1 . A compound of the following formula:

wherein

R1 is a single bond or an (C1-C4) alkylene group;

R2 is selected from the group consisting of:

an (C1-C4) alkyl group substituted with one or more fluorine atoms;

an (C1-C3) alkoxy group substituted with one or more fluorine atoms;

a phenyl group unsubstituted or substituted with one or more R3 groups;

a (C4-C8) cycloalkyl group unsubstituted or substituted with one or more R5 groups;

a (C4-C8) heterocyclyl group unsubstituted or substituted with one or more R6 groups; and

a NR9R10 group;

R3 is selected from the group consisting of:

an (C1-C4) alkyl group unsubstituted or substituted with one or more fluorine atoms;

a cyclopropyl group;

a halogen atom;

an (C1-C3) alkoxy group unsubstituted or substituted with one or more fluorine atoms;

a pentafluorosulfanyl group;

a nitrile group;

a (C1-C3) trialkylsilyl group;

an (C1-C3) alkylsulfonyl group; and

a phenyl group unsubstituted or substituted with a trifluoromethyl group;

R4 is a hydrogen atom or an (C1-C4) alkyl group;

R5 is a fluorine atom or a trifluoromethyl group;

R6 is selected from the group consisting of:

a phenyl group unsubstituted or substituted with one or more fluorine atoms or one or more CF 3 groups;

an (C1-C4) alkyl group substituted with one or more fluorine atoms; and

a fluorine atom;

R7 is selected from the group consisting of:

a hydrogen atom;

a nitrile group;

an (C1-C4) alkyl group unsubstituted or substituted with an (C1-C3) alkoxy group or a hydroxy group;

a COO(C1-C4) alkyl group; and

a CONH2 group;

R8 is a hydrogen atom or an (C1-C4) alkyl group unsubstituted or substituted with a di(C1-C4) alkylamino group;

R9 and R10 are identical or different and are selected from the group consisting of an (C1-C3) alkyl group unsubstituted and an (C1-C3) alkyl group substituted with one or more fluorine atoms; and

R11 is selected from the group consisting of a hydrogen atom, a fluorine atom, and a chlorine atom;

or a pharmaceutically acceptable salt thereof.

2 . The compound according to claim 1 , wherein R4 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

3 . The compound according to claim 1 , wherein R7 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

4 . The compound according to claim 1 , wherein R8 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

5 . The compound according to claim 1 , wherein R11 is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

6 . A compound of formula (I):

wherein

n is 0;

R1 is a single bond;

R2 is selected from the group consisting of:

a phenyl group unsubstituted or substituted with one or more R3 groups;

a (C4-C8) cycloalkyl group unsubstituted or substituted with one or more R5 groups; and

a (C4-C8) heterocyclyl group unsubstituted or substituted with one or more R6 groups;

R3 is selected from the group consisting of:

an (C1-C4) alkyl group unsubstituted or substituted with one or more fluorine atoms;

a cyclopropyl group;

a halogen atom;

an (C1-C3) alkoxy group unsubstituted or substituted with one or more fluorine atoms;

a pentafluorosulfanyl group;

a nitrile group;

a (C1-C3) trialkylsilyl group;

an (C1-C3) alkylsulfonyl group; and

a phenyl group unsubstituted or substituted with a trifluoromethyl group;

R4 is a hydrogen atom or an (C1-C4) alkyl group;

R5 is a fluorine atom or a trifluoromethyl group;

R6 is selected from the group consisting of:

a phenyl group unsubstituted or substituted with one or more fluorine atoms or one or more CF 3 groups;

an (C1-C4) alkyl group substituted with one or more fluorine atoms; and

a fluorine atom;

R7 is selected from the group consisting of:

a hydrogen atom;

a nitrile group;

an (C1-C4) alkyl group unsubstituted or substituted with an (C1-C3) alkoxy group or a hydroxy group;

a COO(C1-C4) alkyl group; and

a CONH2 group;

R8 is a hydrogen atom or an (C1-C4) alkyl group unsubstituted or substituted with a di(C1-C4) alkylamino group; and

R11 is selected from the group consisting of a hydrogen atom, a fluorine atom, and a chlorine atom;

or a pharmaceutically acceptable salt thereof.

7 . The compound according to claim 6 , wherein R2 is a phenyl group substituted with one or more R3 groups, or a pharmaceutically acceptable salt thereof.

8 . The compound according to claim 6 , wherein R3 is an (C1-C4) alkyl group substituted with one or more fluorine atoms, or a pharmaceutically acceptable salt thereof.

9 . A compound selected from:

N-[1-[3-(trifluoromethyl)phenyl]methyl]indol-5-yl]acrylamide;

N-methyl-N-(1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(5,5,5-trifluoropentyl)-1H-indol-5-yl)acrylamide;

N-(1-(1-(3-(trifluoromethyl)phenyl)ethyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-(pentafluoro-16-sulfanyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(4-(pentafluoro-16-sulfanyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(4-(trifluoromethoxy)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-(trifluoromethoxy)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-iodobenzyl)-1H-indol-5-yl)acrylamide;

N-(1-(2-fluoro-5-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(3-methyl-1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-methoxybenzyl)-1H-indol-5-yl)acrylamide;

N-(2-methyl-1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(3-cyano-1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-cyclopropylbenzyl)-1H-indol-5-yl)acrylamide;

N-(2,3-dimethyl-1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-methylbenzyl)-1H-indol-5-yl)acrylamide;

N-(1-Benzyl-1H-indol-5-yl)-acrylamide;

N-(1-(3-(trifluoromethyl)benzyl)-1H-indol-4-yl)acrylamide;

(E)-4-(dimethylamino)-N-(1-(3-(trifluoromethyl)benzyl)-1H-indol-4-yl) but-2-enamide;

N-(1-(3-(trifluoromethyl)benzyl)-1H-indol-6-yl)acrylamide;

N-(1-((4,4-difluorocyclohexyl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-((4-(trifluoromethyl)cyclohexyl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-((1,1-difluorospiro[2.3]hexan-5-yl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-((3-fluorocyclopentyl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-(cyclohexylmethyl)-1H-indol-5-yl)acrylamide;

N-(1-((3-(trifluoromethyl)cyclobutyl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-((3,3-difluorocyclopentyl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-([1,1′-biphenyl]-4-ylmethyl)-1H-indol-5-yl)acrylamide;

N-(1-((3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-((4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-((trans)-4-(trifluoromethyl)cyclohexyl)-1H-indol-5-yl)acrylamide;

N-(1-((cis)-4-(trifluoromethyl)cyclohexyl)-1H-indol-5-yl)acrylamide;

N-(1-((1-(4-(trifluoromethyl)phenyl)piperidin-4-yl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-(2-(methyl (2,2,2-trifluoroethyl)amino)ethyl)-1H-indol-5-yl)acrylamide;

N-(1-(2-(2,2,2-trifluoroethoxy)ethyl)-1H-indol-5-yl)acrylamide;

N-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-indol-5-yl)acrylamide;

N-(1-(4,4-difluorocyclohexyl)-1H-indol-5-yl)acrylamide;

N-(1-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yl)-1H-indol-5-yl)acrylamide;

N-(1-(3-(3,3-difluoropyrrolidin-1-yl)propyl)-1H-indol-5-yl)acrylamide;

N-(1-(4-(trimethylsilyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

N-(1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

N-(1-(6-(trifluoromethyl)pyridin-3-yl)-1H-indol-5-yl)acrylamide;

N-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-indol-5-yl)acrylamide;

N-(1-(pyridin-3-yl)-1H-indol-5-yl)acrylamide;

N-(1-(4-fluorophenyl)-1H-indol-5-yl)acrylamide;

N-(1-(3,4-difluorophenyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-(methylsulfonyl)phenyl)-1H-indol-5-yl)acrylamide;

N-(1-(4-cyanophenyl)-1H-indol-5-yl)acrylamide;

N-(1-(3,5-difluorobenzyl)-1H-indol-5-yl)acrylamide;

N-(1-(3,4-difluorobenzyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-cyanobenzyl)-1H-indol-5-yl)acrylamide;

N-(1-((5-(trifluoromethyl)furan-2-yl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-(thiazol-4-ylmethyl)-1H-indol-5-yl)acrylamide;

N-(1-((2-(trifluoromethyl) thiazol-4-yl)methyl)-1H-indol-5-yl)acrylamide;

N-(1-(3-(trifluoromethyl)benzyl)-1H-indol-7-yl)acrylamide;

N-(1-(3-(methylsulfonyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(3-(methoxymethyl)-1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

methyl 5-acrylamido-1-(3-(trifluoromethyl)benzyl)-1H-indole-3-carboxylate;

N-(1-(3-(trifluoromethyl)phenyl)-1H-indol-6-yl)acrylamide;

N-(1-(4-(pentafluoro-16-sulfanyl)phenyl)-1H-indol-5-yl)acrylamide;

N-(1-(4-(trifluoromethyl)phenyl)-1H-indol-6-yl)acrylamide;

N-(1-(2-methyl-4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

N-(1-(3,5-difluorophenyl)-1H-indol-5-yl)acrylamide;

N-(1-(5-fluoropyridin-3-yl)-1H-indol-5-yl)acrylamide;

N-(1-(2-(trifluoromethyl)pyridin-4-yl)-1H-indol-5-yl)acrylamide;

N-[3-methyl-1-[4-(trifluoromethyl)phenyl]indol-5-yl]acrylamide;

N-[2-methyl-1-[4-(trifluoromethyl)phenyl]indol-5-yl]acrylamide;

N-methyl-N-[2-methyl-1-[4-(trifluoromethyl)phenyl]indol-5-yl]acrylamide;

N-(3-(methoxymethyl)-1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

N-(6-fluoro-1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

N-methyl-N-(1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

(E)-N-(1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl) but-2-enamide;

(E)-4-(dimethylamino)-N-(1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl) but-2-enamide;

N-(6-chloro-1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

N-(6-chloro-1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(7-chloro-1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(6-fluoro-1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)acrylamide;

N-(7-chloro-1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

N-(3-(hydroxymethyl)-1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)acrylamide;

5-acrylamido-1-(3-(trifluoromethyl)benzyl)-1H-indole-3-carboxamide; and

5-acrylamido-1-(4-(trifluoromethyl)phenyl)-1H-indole-3-carboxamide;

and a pharmaceutically acceptable salt thereof.