×

Substituted piperidine compounds useful as modulators of chemokine receptor activity

  • US 20050250792A1
  • Filed: 03/16/2005
  • Published: 11/10/2005
  • Est. Priority Date: 08/24/1999
  • Status: Abandoned Application
0
Associated Cases
0
Associated Defendants
0
Product Citations
0
Petitions
12
Forward Citations
3
Assignments
First Claim
Patent Images

1. A compound of formula (I):

  • embedded image wherein Z is CR4R5, C(O) or CR4R5-Z1;

    Z1 is C1-4 alkylene, C2-4 alkenylene or C(O)NH;

    R1 represents a C1-C12 alkyl group optionally substituted by one or more substituents independently selected from cyano, hydroxyl, C1-C6 alkoxy, C1-C6 alkylthio, C3-7 cycloalkyl, C1-C6 alkoxycarbonyl and phenyl (itself optionally substituted by one or more of halogen, nitro, cyano, C1-C6 alkyl, C1-C6 haloalkyl, phenyl(C1-C6 alkyl), C1-C6 alkoxy, C1-C6 haloalkoxy, S(O)2(C1-C6 alkyl), C(O)NH2, carboxy or C1-C6 alkoxycarbonyl);

    or R1 represents C2-C6 alkenyl optionally substituted by phenyl (itself optionally substituted by one or more of halogen, nitro, cyano, C1-C6 alkyl, C1-C6 haloalkyl, phenyl(C1-C6 alkyl), C1-C6 alkoxy, C1-C6 haloalkoxy, S(O)2(C1-C6 alkyl), C(O)NH2, carboxy or C1-C6 alkoxycarbonyl);

    or R1 represents a 3- to 14-membered saturated or unsaturated ring system which optionally comprises up to two ring carbon atoms that form carbonyl groups and which optionally further comprises up to 4 ring heteroatoms independently selected from nitrogen, oxygen and sulphur, wherein the ring system is optionally substituted by one or more substituents independently selected from;

    halogen, cyano, nitro, oxo, hydroxyl, C1-C8 alkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-6 alkoxy(C1-C6 alkyl), C3-C7 cycloalkyl(C1-C6 alkyl), C1-C6 alkylthio(C1-C6 alkyl), C1-C6 alkylcarbonyloxy(C1-C6 alkyl), C1-C6 alkylS(O)2(C1-C6 alkyl), aryl(C1-C6 alkyl), heterocyclyl(C1-C6 alkyl), arylS(O)2(C1-C6 alkyl), heterocyclylS(O)2(C1-C6 alkyl), aryl(C1-C6 alkyl)S(O)2, heterocyclyl(C1-C6 alkyl)S(O)2, C2-C6 alkenyl, C1-C6 alkoxy, carboxy-substituted C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkoxy, C1-C6 alkylcarboxy-substituted C1-C6 alkoxy, aryloxy, heterocyclyloxy, C1-C6 alkylthio, C3-C7 cycloalkyl(C1-C6 alkylthio), C3-C6 alkynylthio, C1-C6 alkylcarbonylamino, C1-C6 haloalkylcarbonylamino, SO3H, —

    NR7R8, —

    C(O)NR23R24, S(O)2NR18R19, S(O)2R20, R25C(O), carboxyl, C1-C6 alkoxycarbonyl, aryl and heterocyclyl;

    wherein the foregoing aryl and heterocyclyl moieties are optionally substituted by one or more of halogen, oxo, hydroxy, nitro, cyano, C1-C6 alkyl, C1-C6 haloalkyl, phenyl(C1-C6 alkyl), C1-C6 alkoxy, C1-C6 haloalkoxy, S(O)2(C1-C6 alkyl), C(O)NH2, carboxy or C1-C6 alkoxycarbonyl;

    m is 0 or 1;

    Q represents an oxygen or sulphur atom or a group NR9, C(O), C(O)NR9, NR9C(O) or CH═

    CH;

    n is 0, 1, 2, 3, 4, 5 or 6 provided that when n is 0, then m is 0;

    each R2 and R3 independently represents a hydrogen atom or a C1-C4 alkyl group, or (CR2R3)n represents C3-C7 cycloalkyl optionally substituted by C1-C4 alkyl;

    T represents a group NR10, C(O)NR10, NR11C(O)NR10 or C(O)NR10NR11;

    X1, X2, X3 and X4 are, independently, CH2, CHR12 {wherein each R12 is, independently, C1-C4 alkyl or C3-C7 cycloalkyl(C1-C4 alkyl)} or C═

    O;

    or, when they are CHR12, the R12 groups of X1 and X3 or X4, or, X2 and X3 or X4 join to form a two or three atom chain which is CH2CH2, CH2CH2CH2, CH2OCH2 or CH2SCH2;

    provided always that at least two of X1, X2, X3 and X4 are CH2;

    R4 and R5 each independently represent a hydrogen atom or a C1-C4 alkyl group;

    R6 is aryl or heterocyclyl, both optionally substituted by one or more of;

    halogen, cyano, nitro, oxo, hydroxyl, C1-C8 alkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-6 alkoxy(C1-C6 alkyl), C3-C7 cycloalkyl(C1-C6 alkyl), C1-C6 alkylthio(C1-C6 alkyl), C1-C6 alkylcarbonyloxy(C1-C6 alkyl), C1-C6 alkylS(O)2(C1-C6 alkyl), aryl(C1-C6 alkyl), heterocyclyl(C1-C6 alkyl), arylS(O)2(C1-C6 alkyl), heterocyclylS(O)2(C1-C6 alkyl), aryl(C1-C6 alkyl)S(O)2, heterocyclyl(C1-C6 alkyl)S(O)2, C2-C6 alkenyl, C1-C6 alkoxy, carboxy-substituted C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkoxy, C1-C6 alkylcarboxy-substituted C1-C6 alkoxy, aryloxy, heterocyclyloxy, C1-C6 alkylthio, C3-C7 cycloalkyl(C1-C6 alkylthio), C3-C6 alkynylthio, C1-C6 alkylcarbonylamino, C1-C6 C6 haloalkylcarbonylamino, SO3H, —

    NR16R17, —

    C(O)NR21R22, S(O)2NR13R14, S(O)2R15, R26C(O), carboxyl, C1-C6 alkoxycarbonyl, aryl and heterocyclyl;

    wherein the foregoing aryl and heterocyclyl moieties are optionally substituted by one or more of halogen, nitro, cyano, C1-C6 alkyl, C1-C6 haloalkyl, phenyl(C1-C6 alkyl), C1-C6 alkoxy, C1-C6 haloalkoxy, S(O)2(C1-C6 alkyl), C(O)NH2, carboxy or C1-C6 alkoxycarbonyl;

    R7, R8, R9, R10, R11, R13, R14, R16, R17, R18, R19, R21, R22, R23 and R24 are, independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl) or phenyl(C1-C6 alkyl); and

    , R15 and R20 are, independently, C1-C6 alkyl, C1-C6 hydroxyalkyl, C3-C6 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl) or C1-C6 alkyl optionally substituted by phenyl;

    R25 and R26 are, independently, C1-C6 alkyl or phenyl (optionally substituted by one or more of halogen, nitro, cyano, C1-C6 alkyl, C1-C6 haloalkyl, phenyl(C1-C6 alkyl), C1-C6 alkoxy, C1-C6 haloalkoxy, S(O)2(C1-C6 alkyl), C(O)NH2, carboxy or C1-C6 alkoxycarbonyl);

    or a pharmaceutically acceptable salt thereof, or solvate thereof, or a solvate of a salt thereof;

    provided that when T is C(O)NR10 and R1 is optionally substituted phenyl then n is not 0.

View all claims
  • 3 Assignments
Timeline View
Assignment View
    ×
    ×