Novel piperidine derivatives for use in the treatment of chemokine medicated disease states

A compound of formula (I):

• wherein:
• X is CH2, C(O), O, S, S(O), S(O)2 or NR3;
• Y is a bond, C1-6 alkylene optionally substituted by C1-4 alkyl or phenyl, phenylene optionally substituted by halogen, hydroxy, C1-4 alkyl or C1-4 alkoxy, or heterocyclylene optionally substituted by halogen, hydroxy, C1-4 alkyl or C1-4 alkoxy;
• Z is CO2Rb, NHS(O)2CF3, S(O)2OH, OCH2CO2Rb or tetrazolyl;
• R1 is hydrogen, C1-6 alkyl, aryl or heterocyclyl;
• R2 is hydrogen, C1-6 alkyl, aryl or heterocyclyl;
• Ra and Rb are, independently, hydrogen or C1-4 alkyl;
• or when R2 is aryl or heterocyclyl;
• Ra may be C2-3 alkylene forming a ring with an ortho position on R2;
• Rc is hydrogen or hydroxy;
• wherein, unless stated otherwise, the foregoing aryl and heterocyclyl moieties are optionally substituted by:
• halogen, cyano, nitro, hydroxy, oxo, S(O)pR4, OC(O)NR5R6, NR7R8, NR9C(O)R10, NR11C(O)NR12R13, S(O)2NR14R15, NR16S(O)2R17, C(O)NR18R19, C(O)R20, CO2R2′, NR22CO2R23, 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, heterocyclyl, heterocyclyl(C1-4)alkyl, heterocyclyloxy or heterocyclyl(C1-4)alkoxy;
• wherein any of the immediately foregoing phenyl and heterocyclyl moieties are optionally substituted with halogen, hydroxy, nitro, S(O)q(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 R5 and R6 below), 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 R5 and R6 below), 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;
• R3, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R18, R19, R20, R21 and R21 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 and these alkyl groups may join to form a ring as described for R5 and R6 below, 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 groups may join to form a ring as described for R5 and R6 below, 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 R5 and R6 below, 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 R5 and R6 below, 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 groups may join to form a ring as described for R5 and R6 below, 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 R5 and R6 below, 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 NR5R6, NR7R8, NR12R13, NR14R15, NR18R19, may, independently, form a 4-7 membered heterocyclic ring, azetidine, pyrrolidine, piperidine, azepine, morpholine or piperazine, the latter optionally substituted by C1-4 alkyl on the distal nitrogen;
• R4, R17 and R23 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 R5 and R6 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 groups may join to form a ring as described for R5 and R6 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 R5 and R6 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 R5 and R6 above, S(O)2(C1-4 alkyl), S(O)2NH2, S(O)2NH(C1-4alkyl), S(O)2N(C1-4 alkyl)2 and these alkyl groups may join to form a ring as described for R5 and R6 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 R5 and R6 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.