Substituted benzo[b][1,4]oxazines and pyrido[3,2-b][1,4]oxazines as modulators of tumor necrosis factor activity

1. A compound of formula (I):

or an N-oxide or a pharmaceutically acceptable salt thereof,

wherein:

A represents C—R 0 or N;

B represents C—R 1 ;

D represents C—R 2 ;

E represents —CH 2 — or —CH(CH 3 )—;

Q represents —O—;

X represents —C(R 6a )(R 6b )—;

Y represents pyrazolyl, isoxazolyl, imidazolyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyrazinyl, triazolyl, pyridinyl, pyridazinyl or pyrimidinyl, any of which groups may be optionally substituted by one, two or three substituents independently selected from halogen, C 1-6 alkyl, halo(C 1-6 )alkyl, C 1-6 alkoxy, (C 1-6 )alkoxy(C 1-6 )alkoxy(C 1-6 )alkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylsulfonylphenyl, hydroxy(C 1-6 )alkyl, cyano, oxetanyloxy(C 1-6 )alkyl, (C 1-6 )alkylheteroaryl, (C 1-6 )alkoxyheteroaryl, hydroxy(C 1-6 )alkylheteroaryl and morpholinylheteroaryloxy(C 1-6 )alkyl;

Z represents phenyl, pyrrolidinyl, dihydrobenzoisothiazolyl, piperidinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydro-isoquinolinyl, 1,2,3,6-tetrahydropyridinyl, 4,5,6,7-tetrahydro-benzothienyl, 4,5,6,7,8-pentahydrothieno[3,2-c]azepinyl, indolyl, pyrrolo[2,1-f][1,2,4]triazinyl, pyrazolyl, indazolyl, pyrazolo[4,3-b]pyridinyl, 4,5,6,7,8-pentahydrothiazolo[4,5-c]-azepinyl, 4,5,6,7,8-pentahydrothiazolo[5,4-c]azepinyl, pyridinyl, quinolinyl, phthalazinyl or pyrimidinyl, any of which groups may be optionally substituted by one, two or three substituents independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, difluoromethoxy, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkyl-sulfonyl, cyclopropylthio, cyclopropylsulfinyl, cyclopropyl-sulfonyl, hydroxy(C 1-6 )alkyl, oxo, C 2-6 alkylcarbonyl, C 2-6 alkoxycarbonyl, aminocarbonyl, aminosulfonyl, (C 1-6 )alkyl-sulphoximinyl, benzyl, morpholinyl and heteroaryl;

R 0 represents hydrogen, halogen or C 1-6 alkyl;

R 1 and R 2 independently represent hydrogen, halogen, cyano, C 1-6 alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxy, hydroxy(C 1-6 )alkyl, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, pentafluorothio, C 1-6 alkylthio, C 1-6 alkylsulphinyl, C 1-6 alkylsulphonyl, amino, amino(C 1-6 )alkyl, C 1-6 alkylamino, di(C 1-6 )alkylamino, formyl, C 2-6 alkylcarbonyl, carboxy, C 2-6 alkoxycarbonyl, aminocarbonyl, C 1-6 alkyl-aminocarbonyl, di(C 1-6 )alkylaminocarbonyl, aminosulphonyl, C 1-6 alkylaminosulphonyl, di(C 1-6 )alkylaminosulphonyl, (C 1-6 )alkylsulphoximinyl or [(C 1-6 )alkyl][N—(C 1-6 )alkyl]-sulphoximinyl;

R 6a represents hydrogen, halogen, trifluoromethyl or methyl; and

R 6b represents hydrogen, fluoro or methyl.

2. The compound as claimed in claim 1 , wherein the compound is represented by formula (IIA):

or an N-oxide or a pharmaceutically acceptable salt thereof,

wherein:

R 11 represents hydrogen, halogen or C 1-6 alkyl; and

R 16 represents hydrogen, halogen or methyl.

3. A pharmaceutical composition comprising a compound as claimed in claim 1 , or an N-oxide or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable carrier.

4. The pharmaceutical composition as claimed in claim 3 , wherein the pharmaceutical composition further comprises an additional pharmaceutically active ingredient.

5. A method for modulating tumor necrosis factor alpha activity in a patient, which comprises administering to a patient in need of such treatment an effective amount of a compound as claimed in claim 1 , or an N-oxide or a pharmaceutically acceptable salt thereof.

6. The method as claimed in claim 5 , wherein the patient has a disorder selected from the group consisting of an inflammatory disorder, an autoimmune disorder, a neurological disorder, a neurodegenerative disorder, pain, a nociceptive disorder, a cardiovascular disorder, a metabolic disorder, an ocular disorder and an oncological disorder.