Patent GB-0226724-D0 (GB)
Title: Therapeutic agents
IPC: C07D471/04
Filed: 2002-11-15
Abstract: The present invention provides a compound of formula (I): wherein V represents NR<SUP>5</SUP>, O, S, SO or S(O)<SUB>2</SUB>; W and X each independently represent CH or N; Y represents N, CH or C-Ar<SUB>2</SUB>, with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C-Ar<SUB>2</SUB>, with the proviso that when Y is N or CH then Z is C-Ar<SUB>2</SUB>, and with the further proviso that when Y is C-Ar<SUB>2 </SUB>then Z is CH; Ar<SUB>1 </SUB>represents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Ar<SUB>2 </SUB>represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R<SUP>1 </SUP>represents halogen, hydroxy, oxo, C<SUB>1-6</SUB>alkyl, C<SUB>2-6</SUB>alkenyl, C<SUB>2-6</SUB>alkynyl, haloC<SUB>1-6</SUB>alkyl, hydroxyC<SUB>1-6</SUB>alkyl, C<SUB>1-6</SUB>alkoxy, haloC<SUB>1-6</SUB>alkoxy, hydroxyC<SUB>1-6</SUB>alkoxy, C<SUB>3-7</SUB>cycloalkyl, C<SUB>3-7</SUB>cycloalkoxy, C<SUB>3-5</SUB>cycloalkylC<SUB>1-4</SUB>alkyl, cyano, nitro, SR<SUP>6</SUP>, SOR<SUP>6</SUP>, SO<SUB>2</SUB>R<SUP>6</SUP>, COR<SUP>6</SUP>, NR<SUP>3</SUP>COR<SUP>6</SUP>, CONR<SUP>3</SUP>R<SUP>4</SUP>, NR<SUP>3</SUP>SO<SUB>2</SUB>R<SUP>6</SUP>, SO<SUB>2</SUB>NR<SUP>3</SUP>R<SUP>4</SUP>, -(CH<SUB>2</SUB>)<SUB>m</SUB>carboxy, esterified -(CH<SUB>2</SUB>)<SUB>m</SUB>carboxy or -(CH<SUB>2</SUB>)<SUB>m</SUB>NR<SUP>3</SUP>R<SUP>4</SUP>; R<SUP>2 </SUP>represents hydrogen, halogen, hydroxy, C<SUB>1-6</SUB>alkyl, haloC<SUB>1-6</SUB>alkyl, C<SUB>3-7</SUB>cycloalkyl, C<SUB>1-6</SUB>alkoxy, haloC<SUB>1-6</SUB>alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C<SUB>1-6</SUB>alkyl, haloC<SUB>1-6</SUB>alkyl, C<SUB>3-7</SUB>cycloalkyl, C<SUB>1-6</SUB>alkoxy or haloC<SUB>1-6</SUB>alkoxy; R<SUP>3 </SUP>and R<SUP>4 </SUP>are each independently hydrogen, C<SUB>1-6</SUB>alkyl, C<SUB>2-6</SUB>alkenyl, C<SUB>2-6</SUB>alkynyl, C<SUB>3-7</SUB>cycloalkyl or fluoroC<SUB>1-6</SUB>alkyl; or R<SUP>3 </SUP>and R<SUP>4 </SUP>and the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or C<SUB>1-4</SUB>alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O)<SUB>2</SUB>, or NR<SUP>5</SUP>; R<SUP>5 </SUP>represents hydrogen, C<SUB>1-4</SUB>alkyl, hydroxyC<SUB>1-4</SUB>alkyl or C<SUB>1-4</SUB>alkoxyC<SUB>1-4</SUB>alkyl; R<SUP>6 </SUP>represents hydrogen, C<SUB>1-6</SUB>alkyl, fluoroC<SUB>1-6</SUB>alkyl, C<SUB>3-7</SUB>cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C<SUB>1-6</SUB>alkyl, haloC<SUB>1-6</SUB>alkyl, C<SUB>3-7</SUB>cycloalkyl, C<SUB>1-6</SUB>alkoxy or haloC<SUB>1-6</SUB>alkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it.