Tetrahydroimidazopyridine derivatives as modulators of TNF activity
A series of substituted 5,6,7,8-tetrahydroimidazo[1,2-α]pyridine derivatives, being potent modulators of human TNFα 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, or a glucuronide derivative thereof, or a co-crystal thereof:
wherein
R 11 represents hydrogen or halogen;
R 12 represents hydrogen or halogen; and
R 15 represents C 1-6 alkyl or difluoromethoxy;
R 16 represents hydrogen or C 1-6 alkyl;
E represents —CH 2 ;
Q represents —CH 2 — or —CH 2 O—;
Z represents (oxo)oxazolidinylphenyl.
2. The compound as claimed in claim 1 wherein R 11 represents hydrogen.
3. The compound as claimed in claim 1 wherein R 12 represents hydrogen or fluoro.
4. The compound as claimed in claim 1 wherein R 15 represents difluoromethoxy.
5. The compound of claim 1 that is
3-{3-[(3-{[2-(Difluoromethoxy)phenyl]methyl}-5,6,7,8-tetrahydroimidazo[1,2-α]pyridin-2-yl)methoxy]phenyl}oxazolidin-2-one; or
3-{3-[(3-{[2-(Difluoromethoxy)phenyl]methyl}-7-floro-5,6,7,8-tetrahydroimidazo[1,2-α]pyridin-2-yl)methoxy]phenyl}oxazolidin-2-one.
6. A pharmaceutical composition comprising a compound according to claim 1 or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, or a glucuronide derivative thereof, or a co-crystal thereof, in association with a pharmaceutically acceptable carrier.
7. The pharmaceutical composition as claimed in claim 6 further comprising an additional pharmaceutically active ingredient.