Amino-heterocycles as vr-1 antagonists for treating pain

Abstract

The present invention provides a compound of formula (I): wherein V represents NR, O, S, SO or S(O); W and X each independently represent CH or N; Y represents N, CH or C—Ar, 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, with the proviso that when Y is N or CH then Z is C—Ar, and with the further proviso that when Y is C—Arthen Z is CH; Arrepresents 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; Arrepresents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; Rrepresents halogen, hydroxy, oxo, Calkyl, Calkenyl, Calkynyl, haloCalkyl, hydroxyCalkyl, Calkoxy, haloCalkoxy, hydroxyCalkoxy, Ccycloalkyl, Ccycloalkoxy, CcycloalkylCalkyl, cyano, nitro, SR, SOR, SOR, COR, NRCOR, CONRR, NRSOR, SONRR, —(CH)carboxy, esterified —(CH)carboxy or —(CH)NRR; Rrepresents hydrogen, halogen, hydroxy, Calkyl, haloCalkyl, Ccycloalkyl, Calkoxy, haloCalkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, Calkyl, haloCalkyl, Ccycloalkyl, Calkoxy or haloCalkoxy; Rand Rare each independently hydrogen, Calkyl, Calkenyl, Calkynyl, Ccycloalkyl or fluoroCalkyl; or Rand Rand 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 Calkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O), or NR; Rrepresents hydrogen, Calkyl, hydroxyCalkyl or CalkoxyCalkyl; Rrepresents hydrogen, Calkyl, fluoroCalkyl, Ccycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, Calkyl, haloCalkyl, Ccycloalkyl, Calkoxy or haloCalkoxy; 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.