Piperidinyl-morpholinyl derivatives as modulators of chemokine receptor activity

A compound of general formula

• 5
• wherein
• m is 0, 1, 2 or 3;
• each R1 independently represents halogen, cyano, nitro, carboxyl, hydroxyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, —NR6R7, C3-C6 cycloalkylamino, C1-C6 alkylthio, C1-C6 alkylcarbonyl, C1-C6 alkylcarbonylamino, sulphonamido, C1-C6 alkylsulphonyl, —C(O)NR8R9, —NR10C(O)—(NH)pR11, phenyl, or C1-C6 alkyl optionally substituted by at least one substituent selected from carboxyl and C1-C6 alkoxycarbonyl;
• Z1 represents a bond or a group (CH2)q where q is 1 or 2;
• Z2 represents a bond or a group CH2, with the proviso that Z and Z do not both simultaneously represent a bond;
• Q represents an oxygen or sulphur atom or a group CH2 or NH;
• R2 represents an unsaturated 5- to 10-membered ring system which may comprise at least one ring heteroatom selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by at least one substituent selected from halogen, cyano, oxo, nitro, carboxyl, hydroxyl, C2-C6 alkenyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, —NR12R13, C3-C6 cycloalkylamino, C1-C6 alkylthio, C1-C6 alkylcarbonyl, phenylcarbonyl, C1-C6 alkylcarbonylamino, sulphonamido, C1-C6alkylsulphonyl, —C(O)NR14R15. C1-C6alkoxycarbonylC1-C6alkyl, phenyl, methyltetrazolyl, —NHSO2CH3, —NHC(O)NR16R17, —OC(O)NR18R19, —OCH2C(O)NR20R21-NHC(O)OR22, —NHC(O)R23, and C1-C6 alkyl itself optionally substituted by at least one substituent selected from carboxyl and C1-C6 alkoxycarbonyl;
• n is 0, 1 or 2;
• each R3 independently represents a C1-C6 alkyl, C1-C6 alkoxycarbonyl, —CH2OH or carboxyl group;
• R4 and R5 each independently represent a hydrogen atom or a C1-C6 alkyl group;
• R6 and R7 each independently represent a hydrogen atom or a C1-C6 alkyl group, or R6 and R7 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocycle;
• R8 and R9 each independently represent a hydrogen atom or a C1-C6 alkyl group optionally substituted by at least one C1-C6 alkoxycarbonyl;
• p is 0 or 1;
• R10 represents a hydrogen atom or a C1-C6 alkyl group;
• R11 represents a hydrogen atom, or a C1-C6 alkyl group optionally substituted by at least one substituent selected from carboxyl, C1-C6 alkoxy and C1-C6 alkoxycarbonyl;
• R12 and R13 each independently represent a hydrogen atom, a phenyl group, or a C1-C6 alkyl group optionally substituted by at least one substituent selected from carboxyl and C1-C6 alkoxycarbonyl, or R12 and R13 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocycle;
• R14 and R15 each independently represent a hydrogen atom, a phenyl group, a C3-C6 cycloalkyl group, or a C1-C6 alkyl group optionally substituted by at least one substituent selected from carboxyl and C1-C6 alkoxycarbonyl, or R14 and R15 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocycle;
• R16 and R17 each independently represent a hydrogen atom, or a C1-C6 alkyl group optionally substituted by at least one substituent selected from carboxyl and C1--C6 alkoxycarbonyl, or R16 and R17 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocycle;
• R18 and R19 each independently represent a hydrogen atom, or a C1-C6 alkyl group optionally substituted by at least one substituent selected from carboxyl and C1-C6 alkoxycarbonyl, or R18 and R19 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocycle;
• R20 and R21 each independently represent a hydrogen atom, or a C1-C6 alkyl group optionally substituted by at least one substituent selected from carboxyl and C1-C6 alkoxycarbonyl, or R20 and R21 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocycle;
• R22 represents a hydrogen atom, or a C1-C6 alkyl group optionally substituted by at least one substituent selected from carboxyl and C1-C6 alkoxycarbonyl;
• R23 represents a group C1-C6 alkyl, C2-C6 alkenyl, C3-C6 cycloalkyl, adamantyl, C5-C6 cycloalkenyl, phenyl or a saturated or unsaturated 5- to 10-membered heterocyclic ring system comprising at least one ring heteroatom selected from nitrogen, oxygen and sulphur, each group being optionally substituted by at least one substituent selected from nitro, hydroxyl, oxo, halogen, carboxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, phenyl and —NHC(O)—R24;
• and
• R24 represents a C1-C6 alkyl, amino (—NH2) or phenyl group;
• or a pharmaceutically acceptable salt or solvate thereof.