MORPHOLINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS

摘要

The present invention relates to compounds of formula (I) wherein X is a 5- or 6-membered C-linked heteroaromatic ring containing 1 to 4 nitrogen atoms and optionally containing in the ring one oxygen or sulphur atom; Y is a group of the formula -(CH2)nNR<6>R<7>, or a methylene- or ethylene-linked imidazolyl group; Z is hydrogen or C1-4alkyl optionally substituted by a hydroxy group; R<1>, R<2>, R<3>, R<4>, R<5>, R<9a> and R<9b> are a variety of substituents; R<6> is hydrogen, C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, phenyl, or C2-4alkyl substituted by C1-4alkoxy or hydroxy; R<7> is hydrogen, C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, phenyl, or C2-4alkyl substituted by one or two substituents selected from C1-4alkoxy, hydroxy or a 4-, 5- or 6-membered heteroaliphatic ring containing one or two heteroatoms selected from N, O and S; or R<6> and R<7>, together with the nitrogen atom to which they are attached, form a saturated or partially saturated heterocyclic ring or a non-aromatic azabicyclic ring system; and n is zero, 1 or 2; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of pain, inflammation, migraine, emesis and postherapeutic neuralgia.