Trifluoromethylpropanamide derivatives as HTRA1 inhibitors

A compound of formula (I)

• or pharmaceutically acceptable salts thereof, wherein
• R2, R3, R4, R5 and R7 are each independently selected from
• i) H,
• ii) C1-6-alkyl, and
• iii) C3-8-cycloalkyl;
• X is selected from
• i) —O—,
• ii) —S—, and
• iii) —S(O)2—;
• R6 is selected from
• i) aryl substituted with at least one of R12, R13 and R14,
• ii) aryl-C1-6-alkyl substituted with at least one of R12, R13 and R14,
• iii) heteroaryl substituted with at least one of R12, R13 and R14, and
• iv) heteroaryl-C1-6-alkyl substituted with at least one of R12, R13 and R14;
• A is selected from
• i) —O—,
• ii) —CH2—,
• iii) —S(O)2NR10—, and
• iv) —C(O)NR10—;
• R8 is selected from
• i) H, and
• ii) —CH2R9;
• R9 is selected from
• i) H,
• ii) hydroxy,
• iii) amino-C1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C1-6-alkylcarbonyl, C1-6-alkoxycarbonyl, C1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R15, R16 and R17,
• iv) aminocarbonyl substituted on the nitrogen atom by one or two substituents selected from H, C1-6-alkylcarbonyl, C1-6-alkoxycarbonyl, C1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R15, R16 and R17,
• v) aminocarbonyl-C1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C1-6-alkylcarbonyl, C1-6-alkoxycarbonyl, C1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R15, R16 and R17,
• vi) carboxy,
• vii) carboxy-C1-6-alkyl,
• viii) C1-6-alkoxy,
• ix) C1-6-haloalkoxy,
• x) C1-6-alkoxycarbonyl,
• xi) C1-6-alkoxycarbonyl-C1-6-alkyl,
• xii) C3-8-cycloalkyl,
• xiii) aryl substituted with at least one of R15, R16 and R17,
• xiv) aryl-C1-6-alkyl substituted with at least one of R15, R16 and R17,
• xv) aryl-C1-6-alkoxy substituted with at least one of R15, R16 and R17,
• xvi) heteroaryl substituted with at least one of R15, R16 and R17,
• xvii) heteroaryl-C1-6-alkyl substituted with at least one of R15, R16 and R17, and
• xviii) heteroaryl-C1-6-alkoxy substituted with at least one of R15, R16 and R17
• xix) heterocycloalkyl substituted with at least one of R15, R16 and R17,
• xx) heterocycloalkyl-C1-6-alkyl substituted with at least one of R15, R16 and R17,
• xxi) heterocycloalkyl-C1-6-alkoxy substituted with at least one of R15, R16 and R17, and
• xxii) C1-6-alkylsilyloxy;
• R10 is H;
• R11 is selected from
• i) amino-C1-6-alkyl substituted on the nitrogen atom by at least one of R21 and R22,
• ii) C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• iii) C3-8-cycloalkyl-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• iv) C3-8-cycloalkyl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• v) aryl substituted with at least one of R18, R19 and R20,
• vi) aryl-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• vii) aryl-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• viii) aryl-heterocycloalkyl substituted with at least one of R18, R19 and R20
• ix) aryl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• x) aryl(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• xi) aryl(halo)-heterocycloalkyl substituted with at least one of R18, R19 and R20,
• xii) aryloxy-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• xiii) aryloxy-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• xiv) aryloxy-heterocycloalkyl substituted with at least one of R18, R19 and R20,
• xv) aryloxy(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• xvi) aryloxy(halo)-heterocycloalkyl substituted with at least one of R18, R19 and R20
• xvii) aryloxy(halo)-C1-6-alkyl,
• xviii) heterocycloalkyl substituted with at least one of R18, R19 and R20,
• xix) heterocycloalkyl-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• xx) heterocycloalkyl-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• xxi) heterocycloalkyl(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• i) heterocycloalkyl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• ii) heteroaryl substituted with at least one of R18, R19 and R20,
• iii) heteroaryl-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• iv) heteroaryl-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• v) heteroaryl(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• vi) heteroaryl(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• vii) heteroaryloxy-C1-6-alkyl substituted with at least one of R18, R19 and R20,
• viii) heteroaryloxy-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20,
• ix) heteroaryloxy(halo)-C3-8-cycloalkyl substituted with at least one of R18, R19 and R20, and
• x) heteroaryloxy(halo)-C1-6-alkyl substituted with at least one of R18, R19 and R20;
• R12, R13, R14, R15, R16, R17, R18, R19 and R20 are each independently selected from
• i) H,
• ii) cyano,
• iii) halogen,
• iv) oxo,
• v) C1-6-alkyl,
• vi) amino substituted on the nitrogen atom by two substituents independently selected from H, C1-6-alkyl, C1-6-alkoxycarbonyl, arylcarbonyl and heteroarylcarbonyl,
• vii) amino-C1-6-alkyl substituted on the nitrogen atom by two substituents independently selected from H, C1-6-alkyl, C1-6-alkoxycarbonyl, arylcarbonyl and heteroaryl carbonyl,
• viii) C1-6-alkyl,
• ix) halo-C1-6-alkyl,
• x) C3-8-cycloalkyl,
• xi) C1-6-alkoxycarbonyl-C1-6-alkyl,
• xii) carboxy-C1-6-alkyl,
• xiii) C1-6-alkoxycarbonyl-C1-6alkylaminocarbonyl-C1-6alkyl,
• xiv) carboxy-C1-6-alkylaminocarbonyl-C1-6alkyl,
• xv) C1-6-alkoxy,
• xvi) halo-C1-6-alkoxy,
• xvii) C1-6-alkoxycarbonyl-C1-6-alkoxy,
• xviii) carboxy-C1-6-alkoxy,
• xix) C1-6-alkoxycarbonyl-C1-6-alkylaminocarbonyl-C1-6-alkoxy,
• xx) carboxy-C1-6-alkylaminocarbonyl-C1-6-alkoxy, and
• xxi) heterocycloalkyl;
• and
• R21 and R22 are each independently selected from
• i) H,
• ii) C1-6-alkoxycarbonyl,
• iii) carboxy-C1-6-alkyl,
• iv) arylcarbonyl, and
• v) heteroarylcarbonyl;
• with the proviso that N-[(1S)-1-[[(1S)-1-[(2S,4R)-4-benzyloxy-2-[(1-ethyl-3,3,3-trifluoro-2-oxo-propyl)carbamoyl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamoyl]-2-methyl-propyl]pyrazine-2-carboxamide is excluded.