Imidazopyridine derivatives as modulators of TNF activity

A compound represented by formula (IIB) or a pharmaceutically acceptable salt thereof:

• wherein
• E represents —N(R5), —CH2—, —CH(OH)—, —CH(OCH3)—, —CH(OCH2CO2H)—, —CH(NH2)—, —CH(NHCOCH3)—, —CH(CO2H)—, —CH(CO2benzyl)—, —CH(CH3)— or -C(CH3)(OH)—;
• Q represents a covalent bond;
• or Q represents —CH2—, —CH(CN)—, —CH(OH)—, —CH(OCH3)—, —CH2O—,—CH2N(R6)— or —H2OCH2—;
• Z represents hydrogen, halogen or trifluoromethyl;
• or Z represents C1-6 alkyl, C3-7 cycloalkyl, aryl, C3-7 heterocycloalkyl, C3-7 heterocycloalkenyl or heteroaryl, any of which groups is optionally substituted by one or more substituents;
• or Z represents —Z1—Z2 or —Z1—C(O)—Z2, either of which moieties is optionally substituted by one or more halogen, cyano, nitro, C1-6 alkyl, trifluoromethyl, oxo, hydroxy, hydroxy(C1-6)alkyl, C1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C1-3 alkylenedioxy, C1-6 alkylsulfonyl, amino, di(C1-6)alkylamino, di(C1-6)alkylamino(C1-6)alkyl, C2-6 alkylcarbonylamino, C1-6 alkyl-sulfonylamino, formyl, carboxy, C2-6 alkoxycarbonyl, aminocarbonyl, C1-6 alkylamino-carbonyl, di(C1-6)alkylaminocarbonyl, aminocarbonylamino, and hydrazinocarbonyl;
• Z1 represents a divalent radical derived from an aryl, C3-7 heterocycloalkyl or heteroaryl group;
• Z2 represents aryl, C3-7 heterocycloalkyl, C3-7 heterocycloalkenyl or heteroaryl;
• V represents C—R22 or N;
• R5 and R6 independently represent hydrogen or C1-6 alkyl;
• R12 represents hydrogen, halogen, trifluoromethyl or C1-6 alkyl optionally substituted with C2-6 alkoxycarbonyl;
• R15 and R16 independently represent hydrogen, halogen, cyano, nitro, C1-6 alkyl, trifluoromethyl, hydroxy, C1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, amino, C1-6 alkylamino, di(C1-6)alkylamino, arylamino, C2-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, formyl, C2-6 alkylcarbonyl, C3-6 cycloalkylcarbonyl, C3-6 heterocycloalkylcarbonyl, carboxy, C2-6 alkoxycarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di(C1-6)alkylaminocarbonyl, aminosulfonyl, C1-6 alkylaminosulfonyl or di(C1-6alkylaminosufonyl;
• R21 represents hydrogen, halogen, halo(C1-6)alkyl, cyano, C1-6 alkyl, trifluoro-methyl, C2-6 alkenyl, C2-6 alkynyl, hydroxy, hydroxy(C1-6)alkyl, C1-6 alkoxy,(C1-6)alkoxy-(C1-6)alkyl, difluoromethoxy, trifluoromethoxy, trifluoroethoxy, carboxy(C3-7)cycloalkyloxy, C1-6 alkylthio, C1-6 alkylsulphonyl, (C1-6)alkylsulphonyl(C1-6)alkyl, amino, amino-(C1-6)alkyl, C1-6 alkylamino, di(C1-6)alkylamino, (C1-6)alkoxy(C1-6)alkylamino, N-[(C1-6) -alkyl]-N-[hydroxy(C1-6)alkyl]amino, C2-6 alkylcarbonylamino, (C2-6)alkylcarbonylamino-(C1-6)alkyl, C2-6 alkoxycarbonylamino, N-[(C1-6)alkyl]-N-[carboxy(C1-6)alkyl]amino, carboxy(C3-7)cycloalkylamino, carboxy(C3-7)cycloalkyl(C1-6)alkylamino, C1-6 alkyl-sulphonylamino, C1-6 alkylsulphonylamino(C1-6)alkyl, formyl, C2-6 alkylcarbonyl, (C2-6)alkylcarbonyloxy(C1-6)alkyl, carboxy, carboxy(C1-6)alkyl, C2-6 alkoxycarbonyl, morpholinyl(C 1-6)alkoxycarbonyl, C2-6 alkoxycarbonyl(C 1-6)alkyl, C2-6 alkoxycarbonyl-methylidenyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di(C1-6)alkylaminocarbonyl, aminosulphonyl, C1-6 alkylaminosulphonyl or di(C1-6)alkylaminosulphonyl;
• or R21 represents (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-6)alkyl, (C4-7)cycloalkenyl, (C4-9)bicycloalkyl, (C3-7)heterocycloalkyl, (C3-7)heterocycloalkenyl, (C4-9)heterobicycloalkyl or (C4-9)spiroheterocycloalkyl, any of which groups is optionally substituted by one, two or three substituents independently selected from C1-6 alkyl, oxo, carboxy, carboxy(C1-6)alkyl, C2-6 alkoxycarbonyl, tetrazolyl, tetrazolyl(C1-6)alkyl, halogen, halo(C1-6)alkyl, cyano, nitro(C1-6)alkyl, trifluoromethyl, hydroxy, hydroxy(C1-6)alkyl, C1-6 alkoxy, C1-6 alkylsulphonyl, amino, (C2-6)alkylcarbonylamino(C1-6)alkyl, formyl, morpholinyl(C1-6)alkoxycarbonyl, C2-6 alkoxycarbonylmethylidenyl, hydroxyoxadiazolyl, C1-6 alkoxyaminocarbonyl, C1-6 alkylsulphonylaminocarbonyl, aminosulphonyl and C2-6 alkylcarbonylaminosulphonyl;
• R22 represents hydrogen, halogen or C1-6 alkyl;
• and
• R23 represents hydrogen, C1-6 alkyl, trifluoromethyl or C1-6 alkoxy.