Imidazopyridine derivatives as modulators of TNF activity
A series of substituted 3H-imidazo[4,5-c]pyridine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
1. A compound represented by formula (IIA) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof,
wherein
E represents —CH 2 —;
Q represents —CH 2 — or —CH 2 O—;
Z represents hydrogen; or Z represents C 1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one, two or three substituents independently selected from C 1-6 alkoxy and aminocarbonyl;
R 11 represents hydrogen or halogen
R 15 represents halogen or difluoromethoxy, and
R 16 represents hydrogen or halogen.
2. A compound that is
3-[(2,5-Dichlorophenyl)methyl]-2-methylimidazo[4,5-c]pyridine;
{3-[(2,5-Dichlorophenyl)methyl]imidazo[4,5-c]pyridin-2-yl}methanol;
3-[(2,5-Dichlorophenyl)methyl]-2-(pyridin-3-yloxymethyl)imidazo[4,5-c]pyridine;
3-[(2,5-Dichlorophenyl)methyl]-2-[(6-methoxypyridin-3-yl)oxymethyl]imidazo[4,5-c]-pyridine; or
4-({3-[(2,5-Dichlorophenyl)methyl]imidazo[4,5-c]pyridin-2-yl}methoxy)benzamide.
3. A pharmaceutical composition comprising a compound of formula (IIA) as defined in claim 1 or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, in association with a pharmaceutically acceptable carrier.
4. The pharmaceutical composition as claimed in claim 3 further comprising an additional pharmaceutically active ingredient.
5. The compound as claimed in claim 1 wherein Z represents hydrogen; or Z represents methyl, phenyl or pyridinyl, any of which groups may be optionally substituted by one, two or three substituents independently selected from methoxy and aminocarbonyl.