Phenoxymethyl derivatives

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• RA is selected from the group consisting of
• i) C1-C6-alkyl,
• ii) cyano-C1-C6-alkyl,
• iii) C3-C8-cycloalkyl,
• iv) halo-C1-C6-alkoxy,
• v) halo-C1-C6-alkyl,
• vi) aryl substituted with RG, RG1 and RG2,
• vii) heterocycloalkyl substituted with RG, RG1 and RG2, and
• viii) heteroaryl substituted with RG, RG1 and RG2;
• RB is selected from the group consisting of
• i) C1-C6-alkyl,
• ii) C3-C8-cycloalkyl,
• iii) C1-C6-alkylsulfonyl,
• iv) C3-C8-cycloalkylsulfonyl,
• v) C1-C6-alkylsulfonylamino,
• vi) C3-C8-cycloalkylsulfonylamino,
• vii) aminocarbonyl,
• viii) cyano,
• ix) halogen,
• x) halo-C1-C6-alkoxy,
• xi) halo-C1-C6-alkyl,
• xii) heterocycloalkyl, and
• xiii) heteroaryl substituted with one H, C1-C6-alkyl, or trialkylsilyl-C1-C6-alkoxy-C1-C6-alkyl;
• RC and RC1 are independently selected from the group consisting of
• i) H,
• ii) C1-C6-alkyl,
• iii) C3-C8-cycloalkyl,
• iv) halo-C1-C6-alkoxy,
• v) halo-C1-C6-alkyl, and
• vi) halogen;
• or RB and RC together with the carbon atoms to which they are attached form a ring system selected from the group consisting of
• i) C3-C8-cycloalkyl substituted with one to two substituent independently selected from H, C1-C6-alkyl, halo-C1-C6-alkoxy, halo-C1-C6-alkyl and C3-C8-cycloalkyl,
• ii) heterocycloalkyl substituted with one to two substituent independently selected from H, C1-C6-alkyl, halo-C1-C6-alkoxy, halo-C1-C6-alkyl and C3-C8-cycloalkyl,
• iii) aryl substituted with one to two substituent independently selected from H, halogen, C1-C6-alkyl, halo-C1-C6-alkoxy, halo-C1-C6-alkyl and C3-C8-cycloalkyl, and
• iv) heteroaryl substituted with one to two substituent independently selected from H, halogen, C1-C6-alkyl, halo-C1-C6-alkoxy, halo-C1-C6-alkyl, and C3-C8-cycloalkyl;
• W is selected from the ring systems B, C, D, E, F and G;
• A1, A3 and A4 are —CH— and A2 is —CRD2—,
• A1 is —N—, A2 is —CRD2—, A3 is —CH— or —N— and A4 is —CH—,
• A1, A3 and A4 are —CH— and A2 is —N—,
• A1, A2 and A4 are —CH— and A3 is —N—, or
• A1 and A3 are —CH—, A2 is —CRD2— and A4 is —N—;
• one of A5 and A6 is —NRD3— and the other one is —CRLRM—;
• RD2 is selected from the group consisting of
• i) H,
• ii) halogen,
• iii) C1-C6-alkoxy-C1-C6-alkylcarbonyl,
• iv) C1-C6-alkoxycarbonyl,
• v) C1-C6-alkylcarbonyl,
• vi) C3-C8-cycloalkylcarbonyl,
• vii) C1-C6-alkyl,
• viii) C3-C8-cycloalkyl,
• ix) hydroxy-C1-C6-alkoxy,
• x) hydroxy-C1-C6-alkyl(C1-C6-alkyl)amino,
• xi) hydroxy-C1-C6-alkylamino,
• xii) hydroxy-C1-C6-alkyl,
• xiii) dihydroxy-C1-C6-alkoxy,
• xiv) dihydroxy-C1-C6-alkyl(C1-C6-alkyl)amino,
• xv) dihydroxy-C1-C6-alkylamino,
• xvi) dihydroxy-C1-C6-alkyl,
• xvii) halo-C1-C6-alkoxy,
• xviii) halo-C1-C6-alkyl,
• xix) heterocycloalkyl,
• xx) heterocycloalkylcarbonyl, and
• xxi) aminocarbonyl substituted on the nitrogen atom with one to two independently selected C1-C6-alkyl;
• RD3 is selected from the group consisting of
• i) H,
• ii) C1-C6-alkoxy-C1-C6-alkylcarbonyl,
• iii) C1-C6-alkoxycarbonyl,
• iv) C1-C6-alkylcarbonyl,
• v) C3-C8-cycloalkylcarbonyl,
• vi) C1-C6-alkyl,
• vii) C3-C8-cycloalkyl,
• viii) halo-C1-C6-alkoxy,
• ix) halo-C1-C6-alkyl,
• x) hydroxy-C1-C6-alkyl, and
• xi) dihydroxy-C1-C6-alkyl;
• RD4 is selected from the group consisting of
• i) H,
• ii) C1-C6-alkoxy-C1-C6-alkylcarbonyl,
• iii) C1-C6-alkoxycarbonyl,
• iv) C1-C6-alkylcarbonyl,
• v) C3-C8-cycloalkylcarbonyl,
• vi) C1-C6-alkyl,
• vii) C3-C8-cycloalkyl,
• viii) halo-C1-C6-alkoxy,
• ix) halo-C1-C6-alkyl,
• x) heterocycloalkylcarbonyl,
• xi) aminocarbonyl substituted on the nitrogen atom with one to two independently selected C1-C6-alkyl, and
• xii) aryl substituted with one to three substituents independently selected from H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl and halo-C1-C6-alkoxy;
• RD5, RD6 and RD7 are independently selected from the group consisting of
• i) H,
• ii) C1-C6-alkyl,
• iii) C1-C6-alkoxy
• iv) halo-C1-C6-alkoxy,
• v) halo-C1-C6-alkyl,
• vi) C3-C8-cycloalkyl, and
• vii) C3-C8-cycloalkoxy;
• RD8 is selected from the group consisting of
• i) H,
• ii) C1-C6-alkyl,
• iii) C1-C6-alkoxy
• iv) halo-C1-C6-alkoxy,
• v) halo-C1-C6-alkyl,
• vi) C3-C8-cycloalkyl,
• vii) C1-C6-alkoxy-C1-C6-alkylcarbonyl,
• viii) C1-C6-alkoxycarbonyl,
• ix) C1-C6-alkylcarbonyl,
• x) C3-C8-cycloalkylcarbonyl,
• xi) heterocycloalkylcarbonyl, and
• xii) aminocarbonyl substituted on the nitrogen atom with one to two independently selected C1-C6-alkyl;
• RG is selected from the group consisting of
• i) H,
• ii) C1-C6-alkoxy,
• iii) C1-C6-alkoxy-C1-C6-alkylcarbonylamino-C1-C6-alkyl,
• iv) C1-C6-alkoxy-C1-C6-alkylcarbonyl(C1-C6-alkyl)amino-C1-C6-alkyl,
• v) C1-C6-alkoxycarbonyl,
• vi) C1-C6-alkyl,
• vii) C1-C6-alkylsulfonyl,
• viii) C3-C8-cyloalkylsulfonyl,
• ix) carboxy,
• x) cyano,
• xi) C3-C8-cycloalkyl,
• xii) C3-C8-cycloalkoxy,
• xiii) C3-C8-cycloalkylcarbonylamino-C1-C6-alkyl,
• xiv) C3-C8-cycloalkylcarbonyl(C1-C6-alkyl)amino-C1-C6-alkyl,
• xv) C1-C6-alkylcarbonylamino-C1-C6-alkyl,
• xvi) C1-C6-alkylcarbonyl(C1-C6-alkyl)amino-C1-C6-alkyl,
• xvii) halo-C1-C6-alkyl,
• xviii) halo-C1-C6-alkoxy,
• xix) halogen,
• xx) hydroxy,
• xxi) aminocarbonyl substituted on the nitrogen atom with RN and RO,
• xxii) aminocarbonyl-C1-C6-alkoxy substituted on the nitrogen atom with RN and RO,
• xxiii) heteroaryl substituted with one H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl and halo-C1-C6-alkoxy,
• xxiv) heterocycloalkyl-C1-C6-alkoxy substituted with one H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl and halo-C1-C6-alkoxy, and
• xxv) heterocycloalkyl-C1-C6-alkyl substituted with one H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl and halo-C1-C6-alkoxy;
• RG1 and RG2 are independently selected from the group consisting of
• i) H,
• ii) halogen,
• iii) C1-C6-alkyl,
• iv) C3-C8-cycloalkyl,
• v) halo-C1-C6-alkoxy, and
• vi) halo-C1-C6-alkyl;
• RL and RM are independently selected from the group consisting of
• i) H, and
• ii) C1-C6-alkyl;
• RN is selected from the group consisting of
• i) H,
• ii) C1-C6-alkoxy,
• iii) C1-C6-alkoxy-C1-C6-alkyl,
• iv) C1-C6-alkoxycarbonyl-C1-C6-alkyl,
• v) C1-C6-alkyl,
• vi) carboxy-C1-C6-alkyl,
• vii) C3-C8-cycloalkyl,
• viii) C3-C8-cycloalkyl-C1-C6-alkyl,
• ix) hydroxy-C1-C6-alkyl,
• x) phenyl, and
• xi) heteroaryl-C1-C6-alkyl;
• and
• RO is selected from the group consisting of
• i) H, and
• ii) C1-C6-alkyl;
• or RN and RO together with the nitrogen atom to which they are attached form a heterocycloalkyl.

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• (1) RA is selected from the group consisting of
• ix) C1-C6-alkyl,
• x) cyano-C1-C6-alkyl,
• xi) C3-C8-cycloalkyl,
• xii) halo-C1-C6-alkoxy,
• xiii) halo-C1-C6-alkyl,
• xiv) aryl substituted with RG, RG1 and RG2,
• xv) heterocycloalkyl substituted with RG, RG1 and RG2, and
• xvi) heteroaryl substituted with RG, RG1 and RG2;
• and
• RB is selected from the group consisting of
• xiv) C1-C6-alkyl,
• xv) C3-C8-cycloalkyl,
• xvi) C1-C6-alkylsulfonyl,
• xvii) C3-C8-cycloalkylsulfonyl,
• xviii) C1-C6-alkylsulfonylamino,
• xix) C3-C8-cycloalkylsulfonylamino,
• xx) aminocarbonyl,
• xxi) halogen,
• xxii) halo-C1-C6-alkoxy,
• xxiii) halo-C1-C6-alkyl,
• xxiv) heterocycloalkyl, and
• xxv) heteroaryl substituted with one H, C1-C6-alkyl, or trialkylsilyl-C1-C6-alkoxy-C1-C6-alkyl;
• or
• (2) RA is selected from the group consisting of
• i) cyano-C1-C6-alkyl,
• ii) C3-C8-cycloalkyl,
• iii) halo-C1-C6-alkoxy,
• iv) halo-C1-C6-alkyl,
• v) aryl substituted with RG, RG1 and RG2,
• vi) heterocycloalkyl substituted with RG, RG1 and RG2, and
• vii) heteroaryl substituted with RG, RG1 and RG2;
• and
• RB is cyano;
• and:
• RC and RC1 are independently selected from the group consisting of
• vii) H,
• viii) C1-C6-alkyl,
• ix) C3-C8-cycloalkyl,
• x) halo-C1-C6-alkoxy,
• xi) halo-C1-C6-alkyl, and
• xii) halogen;
• or RB and RC together with the carbon atoms to which they are attached form a ring system selected from the group consisting of
• ix) C3-C8-cycloalkyl substituted with one to two substituent independently selected from H, C1-C6-alkyl, halo-C1-C6-alkoxy, halo-C1-C6-alkyl and C3-C8-cycloalkyl,
• x) heterocycloalkyl substituted with one to two substituent independently selected from H, C1-C6-alkyl, halo-C1-C6-alkoxy, halo-C1-C6-alkyl and C3-C8-cycloalkyl,
• xi) aryl substituted with one to two substituent independently selected from H, halogen, C1-C6-alkyl, halo-C1-C6-alkoxy, halo-C1-C6-alkyl and C3-C8-cycloalkyl, and
• xii) heteroaryl substituted with one to two substituent independently selected from H, halogen, C1-C6-alkyl, halo-C1-C6-alkoxy, halo-C1-C6-alkyl, and C3-C8-cycloalkyl;
• W is ring system A:
• RD1 is selected from the group consisting of
• i) H,
• ii) C1-C6-alkyl,
• iii) halo-C1-C6-alkoxy,
• iv) halo-C1-C6-alkyl, and
• v) C3-C8-cycloalkyl,
• RG is selected from the group consisting of
• xxvi) H,
• xxvii) C1-C6-alkoxy,
• xxviii) C1-C6-alkoxy-C1-C6-alkylcarbonylamino-C1-C6-alkyl,
• xxix) C1-C6-alkoxy-C1-C6-alkylcarbonyl(C1-C6-alkyl)amino-C1-C6-alkyl,
• xxx) C1-C6-alkoxycarbonyl,
• xxxi) C1-C6-alkyl,
• xxxii) C1-C6-alkylsulfonyl,
• xxxiii) C3-C8-cyloalkylsulfonyl,
• xxxiv) carboxy,
• xxxv) cyano,
• xxxvi) C3-C8-cycloalkyl,
• xxxvii) C3-C8-cycloalkoxy,
• xxxviii) C3-C8-cycloalkylcarbonylamino-C1-C6-alkyl,
• xxxix) C3-C8-cycloalkylcarbonyl(C1-C6-alkyl)amino-C1-C6-alkyl,
• xl) C1-C6-alkylcarbonylamino-C1-C6-alkyl,
• xli) C1-C6-alkylcarbonyl(C1-C6-alkyl)amino-C1-C6-alkyl,
• xlii) halo-C1-C6-alkyl,
• xliii) halo-C1-C6-alkoxy,
• xliv) halogen,
• xlv) hydroxy,
• xlvi) aminocarbonyl substituted on the nitrogen atom with RN and RO,
• xlvii) aminocarbonyl-C1-C6-alkoxy substituted on the nitrogen atom with RN and RO,
• xlviii) heteroaryl substituted with one H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl and halo-C1-C6-alkoxy,
• xlix) heterocycloalkyl-C1-C6-alkoxy substituted with one H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl and halo-C1-C6-alkoxy, and
• l) heterocycloalkyl-C1-C6-alkyl substituted with one H, C1-C6-alkyl, C3—C— cycloalkyl, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C1-C6-alkyl, C3-C8-cycloalkyl, halo-C1-C6-alkyl and halo-C1-C6-alkoxy;
• RG1 and RG2 are independently selected from the group consisting of
• vii) H,
• viii) halogen,
• ix) C1-C6-alkyl,
• x) C3-C8-cycloalkyl,
• xi) halo-C1-C6-alkoxy, and
• xii) halo-C1-C6-alkyl;
• RN is selected from the group consisting of
• xii) H,
• xiii) C1-C6-alkoxy,
• xiv) C1-C6-alkoxy-C1-C6-alkyl,
• xv) C1-C6-alkoxycarbonyl-C1-C6-alkyl,
• xvi) C1-C6-alkyl,
• xvii) carboxy-C1-C6-alkyl,
• xviii) C3-C8-cycloalkyl,
• xix) C3-C8-cycloalkyl-C1-C6-alkyl,
• xx) hydroxy-C1-C6-alkyl,
• xxi) phenyl, and
• xxii) heteroaryl-C1-C6-alkyl;
• and
• RO is selected from the group consisting of
• iii) H, and
• iv) C1-C6-alkyl;
• or RN and RO together with the nitrogen atom to which they are attached form a heterocycloalkyl.