Difluoroketamide derivatives as HtrA1 inhibitors

A compound of formula (I)

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is selected from
• i) C1-6-alkyl,
• ii) C3-8-cycloalkyl substituted with R24, R25 and R26,
• iii) halo-C1-6-alkyl,
• iv) heterocycloalkyl-C1-6-alkyl substituted with R24, R25 and R26,
• v) aryl-C1-6-alkyl substituted with R24, R25 and R26, and
• vi) heteroaryl-C1-6-alkyl substituted with R24, R25 and R26;
• R2, R3, R4, R6, R7, R9 and R10 are independently selected from
• i) H,
• ii) C1-6-alkyl, and
• iii) C3-8-cycloalkyl;
• R5 is selected from
• i) aryl substituted with R12, R13 and R14,
• ii) aryl-C1-6-alkyl substituted with R12, R13 and R14,
• iii) heteroaryl substituted with R12, R13 and R14, and
• iv) heteroaryl-C1-6-alkyl substituted with R12, R13 and R14,
• R8 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 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 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 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 R15, R16 and R17,
• xiv) aryl-C1-6-alkyl substituted with R15, R16 and R17,
• xv) aryl-C1-6-alkoxy substituted with R15, R16 and R17,
• xvi) heteroaryl substituted with R15, R16 and R17,
• xvii) heteroaryl-C1-6-alkyl substituted with R15, R16 and R17, end
• xviii) heteroaryl-C1-6-alkoxy substituted with R15, R16 and R17
• xix) heterocycloalkyl substituted with R15, R16 and R17,
• xx) heterocycloalkyl —C1-6-alkyl substituted with R15, R16 and R17, and
• xxi) heterocycloalkyl —C1-6-alkoxy substituted with R15, R16 and R17;
• R11 is selected from
• i) amino-C1-6-alkyl substituted on the nitrogen atom by R21 and R22,
• ii) C3-8-cycloalkyl substituted with R18, R19 and R20,
• iii) C3-8-cycloalkyl-C1-6-alkyl substituted with R18, R19 and R20,
• iv) C3-8-cycloalkyl(halo)-C1-6-alkyl substituted with R18, R19 and R20,
• v) aryl substituted with R18, R19 and R20,
• vi) aryl-C1-6-alkyl substituted with R18, R19 and R20,
• vii) aryl-C3-9-cycloalkyl substituted with R18, R19 and R20,
• viii) aryl-heterocycloalkyl substituted with R18, R19 and R20,
• ix) aryl(halo)-C1-6-alkyl substituted with R18, R19 and R20,
• x) aryl(halo)-C3-8-cycloalkyl substituted with R18, R19 and R20,
• xi) aryl(halo)-heterocycloalkyl substituted with R18, R19 and R20,
• xii) aryloxy-C1-6-alkyl substituted with R18, R19 and R20,
• xiii) aryloxy-C3-8-cycloalkyl substituted with R18, R19 and R20,
• xiv) aryloxy-heterocycloalkyl substituted with R18, R19 and R20,
• xv) aryloxy(halo)-C3-8-cycloalkyl substituted with R18, R19 and R20,
• xvi) aryloxy(halo)-heterocycloalkyl substituted with R18, R19 and R20,
• xvii) aryloxy(halo)-C1-6-alkyl,
• xviii) heterocycloalkyl substituted with R18, R19 and R20,
• xix) heterocycloalkyl-C1-6-alkyl substituted with R18, R19 and R20,
• xx) heterocycloalkyl-C3-8-cycloalkyl substituted with R18, R19 and R20,
• xxi) heterocycloalkyl(halo)-C3-8-cycloalkyl substituted with R18, R19 and R20,
• xxii) heterocycloalkyl(halo)-C1-6-alkyl substituted with R18, R19 and R20,
• xxiii) heteroaryl substituted with R18, R19 and R20,
• xxiv) heteroaryl-C1-6-alkyl substituted with R18, R19 and R20,
• xxv) heteroaryl-C3-8-cycloalkyl substituted with R18, R19 and R20,
• xxvi) heteroaryl(halo)-C3-8-cycloalkyl substituted with R18, R19 and R20,
• xxvii) heteroaryl(halo)-C1-6alkyl substituted with R18, R19 and R20,
• xxviii) heteroaryloxy-C1-6-alkyl substituted with R18, R19 and R20,
• xxix) heteroaryloxy-C3-8-cycloalkyl substituted with R18, R19 and R20,
• xxx) heteroaryloxy(halo)-C3-8-cycloalkyl substituted with R18, R19 and R20, and
• xxxi) heteroaryloxy(halo)-C1-6-alkyl substituted with R18, R19 and R20;
• R12, R13, R14, R15, R16, R17, R18, R19, R20, R24, R25 and R26 are 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 heteroarylcarbonyl,
• 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-C1-6-alkylaminocarbonyl-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) C1-6alkoxycarbonyl-C1-6alkylaminocarbonyl-C1-6alkoxy,
• xx) carboxy-C1-6alkylaminocarbonyl-C1-6alkoxy,
• xxi) heterocycloalkyl,
• and
• R21 and R22 are independently selected from
• i) H,
• ii) C1-6-alkoxycarbonyl,
• iii) carboxy-C1-6-alkyl,
• iv) arylcarbonyl, and
• v) heteroarylcarbonyl.