Novel piperidine derivatives as modulators of chemokine receptor ccr5

A compound of formula (I):

• wherein
• A is absent or is (CH2)2;
• R1 is C1-8 alkyl, C(O)NR10R11, C(O)2R12, NR13C(O)R14, NR15C(O)NR16R17, NR18C(O)2R19, heterocyclyl, aryl or heteroaryl;
• R10, R13, R15, R16 and R18 are hydrogen or C1-6 alkyl;
• R11, R12, R14, R17 and R19 are C1-8 alkyl (optionally substituted by halo, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl (optionally substituted by halo), C5-6 cycloalkenyl, S(C1-4 alkyl), S(O)(C1-4 alkyl), S(O)2(C1-4 alkyl), heteroaryl, aryl, heteroaryloxy or aryloxy), aryl, heteroaryl, C3-7 cycloalkyl (optionally substituted by halo or C1-4 alkyl), C4-7 cycloalkyl fused to a phenyl ring, C5-7 cycloalkenyl, or heterocyclyl (itself optionally substituted by oxo, C(O)(C1-6 alkyl), S(O)k(C1-6 alkyl), halo or C1-4 alkyl);
• or R11, R12, R14 and R17 can also be hydrogen;
• or R10 and R11, and/or R16 and R17 may join to form a 4-, 5- or 6-membered ring which optionally includes a nitrogen, oxygen or sulphur atom, said ring being optionally substituted by C1-6 alkyl, S(O)1(C1-6 alkyl) or C(O)(C1-6 alkyl);
• R2 is C1-6 alkyl, phenyl, heteroaryl or C3-7 cycloalkyl;
• R3 is H or C1-4 alkyl;
• R4 is aryl or heteroaryl;
• and
• n is 2, 3 or 4;
• unless specified otherwise aryl, phenyl and heteroaryl moieties are independently optionally substituted by one or more of halo, cyano, nitro, hydroxy, OC(O)NR20R21, NR22R23, NR24C(O)R25, NR26C(O)NR27R28, S(O)2NR29R30, NR31S(O)2R32, C(O)NR33R34, CO2R36, NR37CO2R38, S(O)qR39, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy(C1-6)alkyl, C1-6 alkoxy, C1-6 haloalkoxy, phenyl, phenyl(C1-4)alkyl, phenoxy, phenylthio, phenylS(O), phenylS(O)2, phenyl(C1-4)alkoxy, heteroaryl, heteroaryl(C1-4)alkyl, heteroaryloxy or heteroaryl(C1-4)alkoxy;
• wherein any of the immediately foregoing phenyl and heteroaryl moieties are optionally substituted with halo, hydroxy, nitro, S(C1-4 alkyl), S(O)(C1-4 alkyl), S(O)2(C1-4 alkyl), S(O)2NH2, S(O)2NH(C1-4 alkyl), S(O)2N(C1-4 alkyl)2, cyano, C1-4 alkyl, C1-4 alkoxy, C(O)NH2, C(O)NH(C1-4 alkyl), C(O)N(C1-4 alkyl)2, CO2H, CO2(C1-4 alkyl), NHC(O)(C1-4 alkyl), NHS(O)2(C1-4 alkyl), CF3 or OCF3;
• and
• unless otherwise stated heterocyclyl is optionally substituted by C1-6 alkyl [optionally substituted by phenyl {which itself optionally substituted by halo, C1-4 alkyl, C1-4 alkoxy, cyano, nitro, CF3, OCF3, (C1-4 alkyl)C(O)NH, S(O)2NH2, C1-4 alkylthio, S(O)(C1-4 alkyl) or S(O)2(C1-4 alkyl)} or heteroaryl {which itself optionally substituted by halo, C1-4 alkyl, C1-4 alkoxy, cyano, nitro, CF3, (C1-4 alkyl)C(O)NH, S(O)2NH2, C1-4 alkylthio, S(O)(C1-4 alkyl) or S(O)2(C1-4 alkyl)}], phenyl {optionally substituted by halo, C1-4 alkyl, C1-4 alkoxy, cyano, nitro, CF3, OCF3, (C1-4 alkyl)C(O)NH, S(O)2NH2, C1-4 alkylthio, S(O)(C1-4 alkyl) or S(O)2(C1-4 alkyl)}, heteroaryl {optionally substituted by halo, C1-4 alkyl, C1-4 alkoxy, cyano, nitro, CF3, (C1-4 alkyl)C(O)NH, S(O)2NH2, C1-4 alkylthio, S(O)(C1-4 alkyl) or S(O)2(C1-4 alkyl)}, S(O)2NR40R41, C(O)R42, C(O)2(C1-6 alkyl), C(O)2(phenyl(C1-2 alkyl)) C(O)NHR43, S(O)2R44, NHS(O)2NHR45, NHC(O)R46, NHC(O)NHR47 or NHS(O)2R48, provided none of these last four substituents is linked to a ring nitrogen;
• k, l, and q are, independently, 0, 1 or 2;
• R20, R22, R24, R26, R27, R29, R31, R33, R37 and R40 are, independently, hydrogen or C1-6 alkyl;
• R21, R23, R25, R28, R30, R32, R34, R36, R38, R39, R41, R42, R43, R44, R45, R46, R47 and R48 are, independently, C1-6 alkyl (optionally substituted by halo, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, C5-6 cycloalkenyl, S(C1-4 alkyl), S(O)(C1-4 alkyl), S(O)2(C1-4 alkyl), heteroaryl, phenyl, heteroaryloxy or phenyloxy), C3-7 cycloalkyl, phenyl or heteroaryl;
• wherein any of the immediately foregoing phenyl and heteroaryl moieties are optionally substituted with halo, hydroxy, nitro, S(C1-4 alkyl), S(O)(C1-4 alkyl), S(O)2(C1-4 alkyl), S(O)2NH2, S(O)2NH(C1-4 alkyl), S(O)2N(C1-4 alkyl)2, cyano, C1-4 alkyl, C1-4 alkoxy, C(O)NH2, C(O)NH(C1-4 alkyl), C(O)N(C1-4 alkyl)2, CO2H, CO2(C1-4 alkyl), NHC(O)(C1-4 alkyl), NHS(O)2(C1-4 alkyl), C(O)(C1-4 alkyl), CF3 or OCF3;
• and
• R21, R23, R25, R28, R30, R34, R36, R41, R42, R43, R44, R45, R46 and R47 may additionally be hydrogen;
• or a pharmaceutically acceptable salt thereof or a solvate thereof.