主权项 |
1. A compound of formula I shown below: wherein: W is N or C—R3; X is CH or N; Z is N or C—H; R1 is chloro, (1-6C)alkyl, (1-8C)heteroalkyl, aryl, aryl(1-2C)alkyl, heteroaryl, heteroaryl(1-2C)alkyl, heterocyclyl, heterocyclyl(1-2C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl(1-2C)alkyl, NR7R8, OR9, C(O)R9, C(O)OR9, OC(O)R9, N(R10)OR9, N(R10)C(O)OR9, C(O)N(R10)R9, N(R10)C(O)R9, S(O)pR9 (where p is 0, 1 or 2), SO2N(R10)R9, N(R10)SO2R9, N(R10)SOR9 or SON(R10)R9;
and wherein R1 is optionally substituted by one or more substituent groups selected from fluoro, chloro, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, sulphamoyl, (1-4C)alkyl, (1-4C)alkoxy, S(O)qCH3 (where q is 0, 1 or 2), methylamino, dimethylamino, aryl, aryl(1-2C)alkyl, heteroaryl, heteroaryl(1-2C)alkyl, heterocyclyl, heterocyclyl(1-2C)alkyl, (3-8C)cycloalkyl, and (3-8C)cycloalkyl(1-2C)alkyl,and wherein any (1-4C)alkyl, (1-4C)alkoxy, aryl, heteroaryl, heterocyclyl, or (3-8C)cycloalkyl moiety present within a substituent group on R1 is optionally further substituted by fluoro, chloro, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, sulphamoyl, (1-4C)alkyl, NRaRb, ORa, C(O)Ra, C(O)ORa, OC(O)Ra, N(Rb)ORa, C(O)N(Rb)Ra, N(Rb)C(O)Ra, S(O)pRa (where p is 0, 1 or 2), SO2N(Rb)Ra, or N(Rb)SO2Ra, wherein Ra and Rb are each independently H or (1-4C)alkyl; R3 is hydrogen, (1-4C)alkyl, (3-6C)cycloalkyl, halo, CF3, CN or (1-4C)alkoxy; R4 is hydrogen, (1-3C)alkyl, (1-3C)alkoxy, fluoro, chloro or CF3; Ar has the formula: wherein: (i) all of A1, A2 and A3 are CH; (ii) one of A1, A2 and A3 is N and the others are CH; or (iii) two of A1, A2 and A3 are N and the other is CH; R5 is hydrogen, cyano, (1-3C)alkyl, (1-3C)fluoroalkyl, (1-3C)alkoxy, (1-3C)fluoroalkoxy, halo, (1-3C)alkanoyl, C(O)NR15R16 or S(O)2NR15R16, and wherein R15 and R16 are each independently H or (1-3C)alkyl, and wherein any alkyl or alkoxy moieties present within a R5 substituent group are optionally further substituted by hydroxy or methoxy; R6 is halo, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, sulphamoyl, ureido, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, or a group of the formula:
-L1-L2-R17 whereinL1 is absent or a linker group of the formula —[CR18R19]n— in which n is an integer selected from 1, 2, 3 or 4, and R18 and R19 are each independently hydrogen or (1-2C)alkyl;L2 is absent or is O, S, SO, SO2, N(R20), C(O), C(O)O, OC(O), CH(OR20), C(O)N(R20), N(R20)C(O), N(R20)C(O)N(R21), S(O)2N(R20), or N(R21)SO2, wherein R20 and R21 are each independently hydrogen or (1-2C)alkyl; andR17 is (1-6C)alkyl, aryl, aryl-(1-6C)alkyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-4C)alkyl, heteroaryl, heteroaryl-(1-4C)alkyl, heterocyclyl, heterocyclyl-(1-4C)alkyl,and wherein R17 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, NR22R23, (1-4C)alkoxy, (1-4C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-3C)alkyl, (1-5C)alkanoyl, (1-5C)alkylsulphonyl, heterocyclyl, heterocyclyl-(1-2C)alkyl, heteroaryl, heteroaryl-(1-2C)alkyl, CONR22R23, and SO2NR22R23; wherein R22 and R23 are each independently hydrogen, (1-4C)alkyl, (3-6C)cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl;and wherein when said substituent group comprises an alkyl, cycloalkyl, heterocyclyl or heteroaryl moiety then said moiety is optionally further substituted by hydroxy, fluoro, chloro, cyano, CF3, OCF3, (1-2C)alkyl, (1-2C)alkoxy, SO2(1-2C)alkyl or NReRf (where Re and Rf are each independently hydrogen, (1-3C)alkyl, (3-6C)cycloalkyl, or (3-6C)cycloalkyl(1-2C)alkyl);or R17 is a group having the formula:
-L3-L4-R24 L3 is absent or a linker group of the formula —[CR25R26]n— in which n is an integer selected from 1, 2, 3 and 4, and R25 and R26 are each independently hydrogen or (1-2C)alkyl;L4 is absent or is O, S, SO, SO2, N(R27), C(O), C(O)O, OC(O), CH(OR27), C(O)N(R27), N(R27)C(O), N(R27)C(O)N(R28), S(O)2N(R27), or N(R28)SO2, wherein R27 and R28 are each independently hydrogen or (1-2C)alkyl; andR24 is (1-6C)alkyl, aryl, aryl-(1-6C)alkyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-4C)alkyl, heteroaryl, heteroaryl-(1-4C)alkyl, heterocyclyl, or heterocyclyl-(1-4C)alkyl; R8 and R9 are each independently hydrogen, (1-6C)alkyl, (1-6C)alkoxy, (3-9C)cycloalkyl, (3-9C)cycloalkyl-(1-2C)alkyl, aryl, aryl-(1-2C)alkyl, heterocyclyl, heterocyclyl-(1-2C)alkyl, heteroaryl, or heteroaryl-(1-2C)alkyl, and wherein R8 and R9 are optionally further substituted by one or more substituents selected from hydroxy, fluoro, chloro, cyano, CF3, OCF3 (1-2C)alkyl and (1-2C)alkoxy; R7 and R10 are independently hydrogen, (1-6C)alkyl, (3-6C)cycloalkyl, or (3-6C)cycloalkyl-(1-2C)alkyl, and wherein R7 and R10 are optionally further substituted by one or more substituents selected from hydroxy, fluoro, chloro, cyano, CF3, OCF3, (1-2C)alkyl and (1-2C)alkoxy; subject to the proviso that:
X is only N when Z is N;W is only N when X and Z are both N; andR6 is not methoxy when R1 is S(O)2R9 and R9 is heterocyclyl; or a pharmaceutically acceptable salt or solvate thereof. |