Piperidine derivatives useful as modulators of chemokine receptor activity

A compound of formula (I):

• 25
• wherein:
• T is C(O) or S(O)2;
• W is C(O) or S(O)2;
• X is CH2, O or NH;
• Y is CR11 or N;
• n is 0, 1 or 2;
• m is 1 or, when Y is CR11 m is 0;
• R1 is optionally substituted aryl or optionally substituted heterocyclyl;
• R2, R3, R4, R5, R6, R7 and R8 are, independently, hydrogen or C1-6 alkyl;
• wherein these alkyl groups are optionally substituted by OH, provided that when Y is N then
• R8 does not have a hydroxy on the carbon atom bonded to Y;
• or R2 and R3, R4 and R5, or R6 and R7, together with the atom to which they are attached, form a 3-7 membered carbocyclic ring;
• R4 may additionally be OH or C1-6 alkoxy;
• when Y is CR11 the group R6 may additionally be OH or C1-6 alkoxy;
• provided that only one R4 or R6 is OH;
• R9 is hydrogen or C1-6 alkyl;
• R10 is alkyl, optionally substituted aryl, optionally substituted aralkyl or optionally substituted heterocyclyl;
• R11 is hydrogen or C1-6 alkyl;
• wherein the foregoing aryl and heterocyclyl moieties are optionally substituted by:
• halogen, cyano, nitro, hydroxy, oxo, S(O)pR12, OC(O)NR13R14, NR11R16, NR17C(O)R18, NR19C(O)NR20R21, S(O)2NR22R23, NR24S(O)2R25, C(O)NR26R27, C(O)R28, CO2R29, NR30CO2R31, C1-6 alkyl, CF3, C1-6 alkoxy(C1-6)alkyl, C1-6 alkoxy, OCF3, C1-6 alkoxy(C1-6)alkoxy, C1-6 alkylthio, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl (itself optionally substituted by C1-4 alkyl or oxo), methylenedioxy, difluoromethylenedioxy, phenyl, phenyl(C1-4)alkyl, phenoxy, phenylthio, 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 halogen, hydroxy, nitro, S(O)q(C1-4 alkyl), S(O)2NH2, cyano, C1-4 alkyl, C1-4 alkoxy, C(O)NH2, C(O)NH(C1-4 alkyl), CO2H, CO2(C1-4 alkyl), NHC(O)(C1-4 alkyl), NHS(O)2(C1-4 alkyl), C(O)(C1-4 alkyl), CF3 or OCF3;
• p and q are, independently, 0, 1 or 2;
• R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R26, R27, R28, R29 and R30 are, independently, hydrogen, C1-6 alkyl (optionally substituted by halogen, hydroxy or C3-10 cycloalkyl), CH2(C2-6 alkenyl), phenyl (itself optionally substituted by halogen, hydroxy, nitro, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, S(O)2(C1-4 alkyl), S(O)2NH2, S(O)2NH(C1-4 alkyl), S(O)2N(C1-4alkyl)2, cyano, C1-4 alkyl, 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) or heterocyclyl (itself optionally substituted by halogen, hydroxy, nitro, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, 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);
• alternatively NR13R14, NR15R16, NR20R21, NR22R23, NR26R27, and N(C1-4 alkyl) may, independently, form a 4-7, membered heterocyclic ring, azetidine, pyrrolidine, piperidine, azepine, 1,4-morpholine or 1,4-piperazine, the latter optionally substituted by C1-4alkyl on the distal nitrogen;
• R12, R25 and R31 are, independently, C1-6 alkyl (optionally substituted by halogen, hydroxy or C3-10 cycloalkyl), CH2(C2-6 alkenyl), phenyl (itself optionally substituted by halogen, hydroxy, nitro, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2 (and these alkyl groups may join to form a ring as described for R13 and R14 above), S(O)2(C1-4 alkyl), S(O)2NH2, S(O)2NH(C1-4 alkyl), S(O)2N(C1-4 alkyl)2 (and these alkyl group may join to form a ring as described for R13 and R14 above), cyano, C1-4 alkyl, C1-4 alkoxy, C(O)NH2, C(O)NH(C1-4 alkyl), C(O)N(C1-4 alkyl)2 (and these alkyl groups may join to form a ring as described for R13 and R14 above), CO2H, CO2(C1-4 alkyl), NHC(O)(C1-4 alkyl), NHS(O)2(C1-4 alkyl), C(O)(C1-4 alkyl), CF3 or OCF3) or heterocyclyl (itself optionally substituted by halogen, hydroxy, nitro, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2 (and these alkyl groups may join to form a ring as described for R13 and R14 above), S(Q)2(C1-4 alkyl), S(O)2NH2, S(O)2NH(C1-4 alkyl), S(O)2N(C1-4 alkyl)2 (and these alkyl groups may join to form a ring as described for R13 and R14 above), cyano, C1-4 alkyl, C1-4 alkoxy, C(O)NH2, C(O)NH(C1-4 alkyl), C(O)N(C1-4 alkyl)2 (and these alkyl groups may join to form a ring as described for R13 and R14 above), CO2H, CO2(C1-4 alkyl), NHC(O)(C1-4 alkyl), NHS(O)2(C1-4 alkyl), C(O)(C1-4 alkyl), CF3 or OCF3);
• or an N-oxide thereof;
• or a pharmaceutically acceptable 'salt thereof;
• or a solvate thereof.