| 主权项 |
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:wherein
W is a N or O, wherein N is substituted with —H, C1-C6 alkyl or C3-C5 cycloalkyl; Y is a group —S(O)p— wherein p is 0, 1 or 2; a group —O(CR3R4)n—; a group —(CR5R6)n—; a group —NR7—; a group —OC(O)—; a group —OC(O)NH—; or a group —OC(O)O—; R3, R4, R5 and R6 are each independently —H, —F or C1-C6 alkyl, or, respectively, R3 and R4, or R5 and R6 may form together with the carbon atom to which they are attached a saturated 3-6 membered carbocyclic monocyclic ring optionally substituted by a group C1-C6 alkyl, hydroxyl or halo; n is 0, 1, 2 or 3; R7 is —H, C1-C6alkyl, or C3-C7 cycloalkyl wherein said C1-C6alkyl or C3-C7 cycloalkyl are optionally substituted by a group C1-C3 alkyl, C3-C6 cycloalkyl, hydroxyl, —CN or halo; R1 is a group selected from (IIa)-(IIc): R8 and R9 are each independently —H or C1-C6 alkyl, or R8 and R9 may form together with the nitrogen atom to which they are attached a 4-11-membered saturated monocyclic or a fused or spiro bicyclic ring system optionally containing a further heteroatom which is oxygen or nitrogen, said nitrogen atom being optionally substituted by C1-C6 alkyl; wherein said C1-C6 alkyl groups may be optionally substituted by a group C1-C6 alkyl, C3-C6 cycloalkyl, hydroxyl or halo; X1, X2, X3, X4 and X5 are each independently a carbon atom, a nitrogen atom, a group —(CH)— or a group —NH—; such that each combination thereof forms an aromatic ring system; R10 is selected from the group consisting of —H, —CN, —NRARB, —N(RC)(C2-C6alkylene)-NRARB, —N(RC)(C3-C7cycloalkylene)-NRARB, —(C1-C6alkylene)-NRARB, —(C3-C7cycloalkylene)-NRARB, —O—(C2-C6alkylene)-NRARB, —O—(C3-C7cycloalkylene)-NRARB, —S—(C2-C6alkylene)-NRARB, —S—(C3-C7cycloalkylene)-NRARB, —N(RC)C(O)—(C1-C6alkylene)-NRARB, —N(RC)C(O)—(C3-C7cycloalkylene)-NRARB, —C(O)N(RC)—(C2-C6alkylene)-NRARB, —C(O)N(RC)—(C3-C7cycloalkylene)-NRARB, —C(O)N(RC)—(C2-C6alkylene)-ORD, —C(O)N(RC)—(C3-C7cycloalkylene)-ORD, —N(RC)C(O)NRARB, —C(O)NRARB, —N(RC)C(O)N(RC)—(C2-C6alkylene)-NRARB, —N(RC)C(O)N(RC)—(C3-C7cycloalkylene)-NRARB, —(C2-C6alkylene)-ORD, —(C3-C7cycloalkylene)-ORD, —O—(C2-C6alkylene)-ORD, —O—(C3-C7cycloalkylene)-ORD, —S—(C2-C6alkylene)-ORD, —S—(C3-C7cycloalkylene)-ORD, —N(RC)S(O)2—(C1-C6alkylene)-NRARB, —N(RC)S(O)2—(C3-C7cycloalkylene)-NRARB, —S(O)2N(RC)—(C2-C6alkylene)-NRARB, —S(O)2N(RC)—(C3-C7cycloalkylene)-NRARB, —S(O)2N(RC)—(C2-C6alkylene)-ORD, —S(O)2N(RC)—(C3-C7cycloalkylene)-ORD, —N(RC)S(O)2—(C2-C6alkylene)-ORD, —N(RC)S(O)2—(C3-C7cycloalkylene)-ORD, —S(O)2N(RARB), —N(RC)S(O)2RD, —N(RC)C(O)RC, —ORS, —(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(C1-C6alkyl), (C5-C7heterocycloalkyl)(C3-C6cycloalkyl)-, and C3-C7 heterocycloalkylcarbonyl; wherein any of said C1-C6alkyl, C3-C6cycloalkyl, —(C1-C6alkylene)-(C2-C6alkylene)-, —(C3-C7cycloalkylene)-, —(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(C1-C6 alkyl), (C5-C7 heterocycloalkyl)-(C3-C6 cycloalkyl) and (C3-C7heterocycloalkyl)carbonyl portion in the above listed groups may be optionally substituted by a group C1-C6 alkyl, C3-C7 cycloalkyl, hydroxyl or halo; R11 is linked to X4 and is selected from the group consisting of —H; —CN; C1-C6 alkyl which is substituted by a group selected from the group consisting of —CN, —ORC, —SRS, and halo; C3-C6cycloalkyl which is substituted by a group selected from the group consisting of C1-C4 alkyl, —CN, —ORC, —SRD, an dhalo; —NRARB; —N(RC)(C2-C6alkylene)-NRARB; —N(RC)(C3-C7cycloalkylene)-NRARB; —(C1-C6alkylene)-NRARB; —(C3-C7cycloalkylene)-NRARB; —O—(C2-C6alkylene)-NRARB; —O—(C3-C7cycloalkylene)-NRARB; —S—(C2-C6alkylene)-NRARB; —S—(C3-C7cycloalkylene)-NRARB; —N(RC)C(O)—(C1-C6alkylene)-NRARB; —N(RC)C(O)—(C3-C7cycloalkylene)-NRARB; —C(O)N(RC)—(C2-C6alkylene)-NRARB; —C(O)N(RC)—(C3-C7cycloalkylene)-NRARB; —C(O)N(RC)—(C2-C6alkylene)-ORD; —C(O)N(RC)—(C3-C7cycloalkylene)-ORD; —N(RC)C(O)N(RARB), —C(O)N(RARB); —N(RC)C(O)N(RC)—(C2-C6alkylene)-NRARB; —N(RC)C(O)N(RC)—(C3-C7cycloalkylene)-NRARB; —O—(C2-C6alkylene)-ORD; —O—(C3-C7cycloalkylene)-ORD; —S—(C2-C6alkylene)-ORD; —S—(C3-C7cycloalkylene)-ORD; —N(RC)S(O)2—(C1-C6alkylene)-NRARB; —N(RC)S(O)2—(C3-C7cycloalkylene)-NRARB; S(O)2N(RC)—(C2-C6alkylene)-NRARB; —S(O)2N(RC)—(C3-C7cycloalkylene)-NRARB; —S(O)2N(RC)—(C2-C6alkylene)-ORD; —S(O)2N(RC)—(C3-C7cycloalkylene)-ORD; —N(RC)S(O)2—(C2-C6alkylene)-ORD; —N(RC)S(O)2—(C3-C7cycloalkylene)-ORD; —S(O)2N(RARB); —N(RC)S(O)2RD; —N(RC)C(O)RC; ORC; SRC; —(C3-C7heterocycloalkyl); (C5-C7heterocycloalkyl)-(C1-C6alkyl); (C5-C7heterocycloalkyl)(C3-C6cycloalkyl); and (C3-C7 heterocycloalkyl)carbonyl, wherein any of said C1-C6alkyl, C3-C6cycloalkyl, —(C1-C6alkylene)-(C2-C6alkylene)-, —(C3-C7cycloalkylene)-, —(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(C1-C6 alkyl), (C5-C7 heterocycloalkyl)-(C3-C6 cycloalkyl) and (C3-C7heterocycloalkyl)carbonyl portion in the above listed groups may be optionally substituted by one, two or three groups R25 which are independently selected from the group consisting of C1-C6 alkyl, (C1-C3) haloalkyl, (C1-C4)hydroxyalkyl, C3-C7 cycloalkyl, hydroxyl, —CN, ORD and halo; or R11 is linked to X4 and is phenyl or 5- or 6-membered monocyclic heteroaryl, wherein said phenyl or 5- or 6-membered monocyclic heteroaryl is substituted by a group selected from the group consisting of C1-C6 alkyl which is substituted by a group —CN; C3-C6 cycloalkyl which is substituted by a group selected from the group consisting of —CN, —ORC, —SRC and halo; —N(RC)(C2-C6alkylene)-NRARB; —N(RC)(C3-C7cycloalkylene)-NRARB; —(C1-C6alkylene)-NRARB; —(C3-C7cycloalkylene)-NRARB; —O—(C3-C7cycloalkylene)-NRARB; —S—(C2-C6alkylene)-NRARB; —S—(C3-C7cycloalkylene)-NRARB; —N(RC)C(O)—(C1-C6alkylene)-NRARB; —N(RC)C(O)—(C3-C7cycloalkylene)-NRARB; C(O)N(RC)—(C2-C6alkylene)-NRARB; —C(O)N(RC)—(C3-C7cycloalkylene)-NRARB, —C(O)N(RC)—(C2-C6alkylene)-ORD; —C(O)N(RC)—(C3-C7cycloalkylene)-ORD; —N(RC)C(O)N(RC)—(C2-C6alkylene)-NRARB; —N(RC)C(O)N(RC)—(C3-C7cycloalkylene)-NRARB; —O—(C3-C7cycloalkylene)-ORD; —S—(C3-C7cycloalkylene)-ORD; —N(RC)S(O)2—(C1-C6alkylene)-NRARB, —N(RC)S(O)2—(C3-C7cycloalkylene)-NRARB, —S(O)2N(RC)—(C2-C6alkylene)-NRARB; —S(O)2N(RC)—(C3-C7cycloalkylene)-NRARB; —S(O)2N(RC)—(C2-C6alkylene)-ORD; —S(O)2N(RC)—(C3-C7cycloalkylene)-ORD; —N(RC)S(O)2—(C2-C6alkylene)-ORD; —N(RC)S(O)2—(C3-C7cycloalkylene)-ORD; —N(RC)S(O)2RD; —(C3-C7heterocycloalkyl); (C5-C7heterocycloalkyl)-(C1-C6alkyl); (C5-C7heterocycloalkyl)(C3-C6cycloalkyl); and (C3-C7heterocycloalkyl)carbonyl, wherein any of said C1-C6alkyl, C3-C6cycloalkyl, —(C1-C6alkylene)-(C2-C6alkylene)-, —(C3-C7cycloalkylene)-, —(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(C1-C6 alkyl), (C5-C7 heterocycloalkyl)-(C3-C6 cycloalkyl) and (C3-C7heterocycloalkyl)carbonyl portion in the above listed groups may be optionally substituted by one, two or three groups R25 which are independently selected from the group consisting of C1-C6alkyl, (C1-C3) haloalkyl, (C1-C4)hydroxyalkyl, C3-C7cycloalkyl, hydroxyl, —CN, ORD and halo; RA and RB are at each occurrence independently —H, C1-C6 alkyl or C3-C7 cycloalkyl, said C1-C6 alkyl and C3-C7 cycloalkyl being optionally substituted by a group C1-C3 alkyl, C3-C7cycloalkyl, —ORD, —CN or halo; alternatively, RA and RB, may form together with the nitrogen atom to which they are attached an azetidine or a 4-11-membered saturated heterocyclic monocyclic or bicyclic ring system which is optionally substituted by one or more group —ORD, —CN, halo, C1-C6 alkyl, (C1-C6)hydroxyalkyl or C3-C7 cycloalkyl, said C1-C6 alkyl and C3-C7 cycloalkyl being optionally substituted by a group C1-C3 alkyl, C3-C7cycloalkyl, —ORD, —CN or halo; and which 6-11-membered saturated heterocyclic monocyclic or bicyclic ring optionally contains a further heteroatom which is oxygen or nitrogen, said nitrogen atom optionally substituted by C1-C6 alkyl or C3-C6 cycloalkyl, wherein any of said C1-C6 alkyl or C3-C6 cycloalkyl may be optionally substituted by a group C1-C6 alkyl, C3-C7 cycloalkyl, —ORD, —CN, or halo; or RA and RB may be linked to one carbon atom of the —(C1-C6alkylene)-, —(C2-C6alkylene)- or —(C3-C7cycloalkylene)- portion of the group linked to the nitrogen to which they are connected to form a saturated cycle of up to 6 ring atoms; RC is at each occurrence independently —H, C1-C6alkyl, (C1-C4)hydroxyalkyl or C3-C6 cycloalkyl, said C1-C6 alkyl and C3-C6 cycloalkyl being optionally substituted by a group C1-C3 alkyl, —ORD, —CN or halo; alternatively RC may be linked to one carbon atom of the —(C2-C6alkylene)- or —(C3-C7cycloalkylene)- portion of the group linked to the nitrogen to which they are connected to form a saturated cycle of up to 6 ring atoms RD is at each occurrence independently —H, —CH3 or —C2H5; R12 and R13 are independently —H, C1-C6 alkyl, or halogen; A is a divalent cycloalkylene radical having 5, 6 or 7 ring atoms; said cycloalkylene ring being attached to W and Y and fused to a phenyl ring or to a monocyclic heteroaryl ring having 5 or 6 ring atoms, said phenyl or heteroaryl ring being optionally substituted by one or two groups R24; R24 is at each occurrence independently selected from the group consisting of C1-C6 alkyl, halogen and —CN; R2 is a radical of formula (IIIb): wherein R17 is selected from the group consisting of a lone electron pair, —H, —CF3, —NRERF, —(C3-C7cycloalkyl), —(C3-C7heterocycloalkyl), aryl or heteroaryl wherein any of said —(C3-C7cycloalkyl), —(C3-C7heterocycloalkyl), aryl or heteroaryl may be optionally substituted by a group C1-C6 alkyl, C3-C7 cycloalkyl or halo; or R17 is a group of general formula (IV) wherein R20 is selected in the group consisting of —F, —CH3, —C2H5, —CH2OH, —CH2OMe, —CF2CF3, —CH2SCH3, —SCH3 and —SC2H5; R21 is —CH3 or —C2H5; or R20 and R21 as defined above may form together with the carbon atom to which they are attached a saturated 3-7-membered monocyclic ring; RE and RF are each independently C1-C6 alkyl, optionally substituted by a group C1-C3 alkyl, —ORG, —CN or halo; alternatively RE and RF may form together with the nitrogen atom to which they are attached a 5-11-membered saturated monocyclic or bicyclic heterocyclic ring system which is optionally substituted by one or more groups —ORG, —CN, halo, C1-C6 alkyl or C3-C7 cycloalkyl, said C1-C6 alkyl and C3-C7 cycloalkyl being optionally substituted by a group C1-C3 alkyl, C3-C7cycloalkyl, —ORG, —CN or halo; and which 5-11-membered saturated monocyclic or bicyclic heterocyclic ring optionally contains a further heteroatom which is oxygen or nitrogen, said nitrogen atom optionally substituted by C1-C6 alkyl or C3-C6 cycloalkyl, wherein any of such C1-C6 alkyl or C3-C6 cycloalkyl may be optionally substituted by a group C1-C6 alkyl or C3-C7 cycloalkyl; RG is —H, —CH3 or —C2H5; R18 is selected from the group consisting of aryl, heterocycloalkyl and heteroaryl, wherein any of said aryl, heterocycloalkyl or heteroaryl is substituted by two or more groups independently selected from the group consisting of —CN, —OH, ═O, halo, —COORM, C1-C6 alkyl, C3-C6cycloalkyl, —O—(C1-C6alkyl), —(C1-C6)hydroxyalkyl, —O—(C3-C6cycloalkyl), —S—(C1-C6alkyl), —S—(C3-C6cycloalkyl), —NRHRJ, —N(RL)(C2-C6alkylene)-NRHRJ, —N(RL)(C3-C7cycloalkylene)-NRHRJ, —(C1-C6alkylene)-NRHRJ, —(C3-C7cycloalkylene)-NRHRJ, —O—(C2-C6alkylene)-NRHRJ, —O—(C3-C7cycloalkylene)-NRHRJ, —S—(C2-C6alkylene)-NRHRJ, —S—(C3-C7cycloalkylene)-NRHRJ, —N(RL)C(O)—(C1-C6alkylene)-NRHRJ, —N(RL)C(O)—(C3-C7cycloalkylene)-NRHRJ, —C(O)N(RL)—(C2-C6alkylene)-NRHRJ, —C(O)N(RL)—(C3-C7cycloalkylene)-NRHRJ, —C(O)N(RL)—(C2-C6alkylene)-ORM, —C(O)N(RL)—(C3-C7cycloalkylene)-ORM, —N(RL)C(O)N(RHRJ), —C(O)N(RHRJ), —N(RL)C(O)N(RL)—(C2-C6alkylene)-NRHRJ, —N(RL)C(O)N(RL)—(C3-C7cycloalkylene)-NRHRJ, —O—(C2-C6alkylene)-ORM, —O—(C3-C7cycloalkylene)-ORM, —S—(C2-C6alkylene)-ORM, —S—(C3-C7cycloalkylene)-ORM, —N(RL)S(O)2—(C1-C6alkylene)-NRHRJ, —N(RL)S(O)2—(C3-C7cycloalkylene)-NRHRJ, —S(O)2N(RL)—(C2-C6alkylene)-NRHRJ, —S(O)2N(RL)—(C3-C7cycloalkylene)-NRHRJ, —S(O)2NRL)—(C2-C6alkylene)-ORM, —S(O)2N(RL)—(C3-C7cycloalkylene)-ORM, —N(RL)S(O)2—(C2-C6alkylene)-ORM, —N(RL)S(O)2—(C3-C7cycloalkylene)-ORM, —S(O)2N(RHRJ), —N(RL)S(O)2RL, —N(RL)C(O)RL, ORL, SRL, —(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(C1-C6 alkyl) and (C5-C7 heterocycloalkyl)-(C3-C6 cycloalkyl), wherein any of said C1-C6alkyl, C3-C6cycloalkyl, —(C1-C6alkylene)-, —(C2-C6alkylene)-, —(C3-C7cycloalkylene)-, —(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(C1-C6 alkyl) and (C5-C7 heterocycloalkyl)-(C3-C6 cycloalkyl) portion in the above listed groups may be optionally substituted by a group C1-C6 alkyl, C3-C7 cycloalkyl, —ORL or halo; RH and RJ are at each occurrence independently —H, C1-C6 alkyl or C3-C6 cycloalkyl, said C1-C6 alkyl or C3-C6 cycloalkyl being optionally substituted by a group C1-C3 alkyl, —ORM, CN or halo; alternatively, RH and RJ may also form together with the nitrogen atom to which they are attached a 4-11-membered saturated monocyclic or bicyclic heterocyclic ring system which is optionally substituted by one or more groups —ORM, —CN, halo, NRORP, C1-C6 alkyl or C3-C7 cycloalkyl, said C1-C6 alkyl and C3-C7 cycloalkyl being optionally substituted by a group C1-C3 alkyl, C3-C7cycloalkyl, —ORM, CN or halo; and which 6-11-membered saturated monocyclic or bicyclic heterocyclic ring optionally contains a further heteroatom which is oxygen or nitrogen, said nitrogen atom optionally substituted by C1-C6 alkyl or C3-C6 cycloalkyl, wherein any of said C1-C6 alkyl or C3-C6 cycloalkyl may be optionally substituted by a group C1-C6 alkyl, C3-C7 cycloalkyl, —ORM, CN, or halo; or RH and RJ may be linked to one carbon atom of the —(C1-C6alkylene)-, —(C2-C6alkylene)- or —(C3-C7cycloalkylene)-portion of the group linked to the nitrogen to which they are connected to form a saturated cycle of up to 6 ring atoms; RL is at each occurrence independently —H, C1-C6 alkyl or C3-C6 cycloalkyl, said C1-C6 alkyl or C3-C6 cycloalkyl being optionally substituted by a group C1-C3 alkyl, —ORM, —CN or halo; RM is at each occurrence independently —H, C1-C6 alkyl or C3-C6 cycloalkyl, said C1-C6 alkyl or C3-C6 cycloalkyl being optionally substituted by a group hydroxyl, —CN or halo; RO and RP are each independently C1-C6 alkyl or C1-C6 cycloalkyl, optionally substituted by a group C1-C3 alkyl, —ORQ, —CN or halo; alternatively, RO and RP may form together with the nitrogen atom to which they are attached a 4-8-membered saturated monocyclic heterocyclic ring system which is optionally substituted by one or more groups —ORQ, —CN, halo, C1-C6 alkyl or C3-C7 cycloalkyl, and which 4-8-membered saturated monocyclic heterocyclic ring optionally contains a further heteroatom which is oxygen or nitrogen, said nitrogen atom optionally substituted by C1-C6 alkyl or C3-C6 cycloalkyl; RQ is —H, —CH3 or —C2H5; z1, z2, z3, and z4 are independently selected from the group consisting of C, N, S, O, a group —CH— and a group —NH—, in such a combination that the resulting ring formed is an aromatic system; with the proviso that when Y is a group —O(CR3R4)n—, n is 1 and R10 is —NRARB, —N(RC)C(O)—(C1-C6alkylene)-NRARB, —N(RC)C(O)—(C3-C7cycloalkylene)-NRARB, —N(RC)C(O)N(RARB), —N(RC)C(O)N(RC)—(C2-C6alkylene)-NRARB, —N(RC)C(O)N(RC)—(C3-C7cycloalkylene)-NRARB or —N(RC)C(O)RC, then X1 is nitrogen. |
