Benzotriazole derivatives as modulators of TNF activity

1. A compound of formula (IIB) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof,

wherein

V is C—R 22 or N;

R 21 is hydroxy(C 1-6 )alkyl: or R 21 is (C 3-7 )heterocyclo-alkyl, which group may be optionally substituted by one, two or three substituents independently selected from C 1-6 alkylsulphonyl, oxo and carboxy;

R 22 is hydrogen, halogen or C 1-6 alkyl;

R 23 is hydrogen, C 1-6 alkyl, trifluoromethyl or C 1-6 alkoxy;

E is —CH 2 ; and

R 12 is hydrogen, fluoro, chloro, trifluoromethyl, methyl or ethoxycarbonylethyl;

R 15 is hydrogen, halogen, C 1-6 alkyl, trifluoromethyl, C 1-6 alkoxy, difluoromethoxy or trifluoromethoxy; and

R 16 is hydrogen, halogen, cyano, C 1-6 alkyl, trifluoro-methyl, difluoromethoxy or amino.

2. The compound as claimed in claim 1 represented by formula (IIC), or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof:

wherein

T is —CH 2 or —CH 2 CH 2 —;

U is C(O) or S(O) 2 ;

W is O, N(R 31 ) or C(R 32 )(R 33 );

R 31 is hydrogen or C 1-6 alkylsulphonyl;

R 32 is carboxy;

R 33 is hydrogen.

3. The compound as claimed in claim 1 wherein R 15 is difluoromethoxy.

4. A compound that is,

4-[5-(1-{[2-(Difluoromethoxy)phenyl]methyl}benzotriazol-6-yl)pyrimidin-2-yl]-morpholine,

1-[5-(1-{[2-(Difluoromethoxy)phenyl]methyl}benzotriazol-6-yl)pyrimidin-2-yl]-piperidine-4-carboxylic acid,

4-[5-(1-{[2-(Difluoromethoxy)phenyl]methyl}benzotriazol-6-yl)pyrimidin-2-yl]-piperazin-2-one,

1-{[2-(Difluoromethoxy)phenyl]methyl}-6-[2-(piperazin-1-yl)pyrimidin-5-yl]-benzotriazole, or

1-{[2-(Difluoromethoxy)phenyl]methyl}-6-{2-[4-(methylsulfonyl)piperazin-1-yl]-pyrimidin-5-yl}benzotriazole.

5. A pharmaceutical composition comprising a compound of formula (IIB) as defined in claim 1 or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, in combination with a pharmaceutically acceptable carrier.

6. A pharmaceutical composition as claimed in claim 5 further comprising an additional pharmaceutically active ingredient.

7. A method for the treatment of an inflammatory or autoimmune disorder, which comprises administering to a patient in need of such treatment an effective amount of a compound of formula (IIB) as defined in claim 1 or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, wherein the inflammatory or autoimmune disorder is selected from the group consisting of rheumatoid arthritis and Crohn's disease.

8. The method according to claim 7 , wherein said method further comprises the administration of an additional pharmaceutically active agent.