SPIRO-AZACYCLIC DERIVATIVES, THEIR PREPARATION AND THEIR USE AS TACHYKININ ANTAGONISTS

摘要

Substituted spiro-azacyclic derivatives of structural formula (I), wherein R1 represents hydrogen, hydroxy, C¿1-6?alkyl, C2-6alkenyl, C3-7cycloalkyl optionally substituted alkyl, optionally substituted alkoxy, C2-6alkenyloxy, C3-7cycloalkoxy, phenoxy, benzyloxy, cyano, halogen, NR?11COR14, NRaRb, SRa, SORa, SO¿2Ra or OSO¿2R?a; R2 represents hydrogen, halogen, C¿1-6?alkyl or C1-6alkoxy; or when R?2¿ is adjacent to R1, they may be joined together such that there is formed a 5- or 6-membered saturated or unsaturated ring containing one or two oxygen atoms; R3 represents an optionally substituted 5- or 6-membered aromatic heterocyclic group containing 1, 2, 3 or 4 heteroatoms, selected from nitrogen, oxygen and sulphur; R4 represents hydrogen, halogen, C¿1-6?alkyl, C1-6alkoxy, trifluoromethyl, trifluoromethoxy, nitro, cyano, SR?a, SORa, SO¿2Ra, CO2R?a, CONRaRb, C¿2-6alkenyl, C2-6alkynyl or C1-4alkyl substituted by C1-4alkoxy; R5 represents hydrogen, halogen, C¿1-6?alkyl, trifluoromethyl or C1-6alkoxy substituted by C1-4alkoxy; R?6¿ represents hydrogen, CORa, CO2Ra, COCONRaRb, COCO¿2R?a, optionally substituted C¿1-6?alkyl; or R?6¿ represents a group of the formula -CH¿2?C CCH2NR?7R8; or R6¿ represents C¿1-6?alkyl, optionally substituted by oxo, substituted by a 5-membered or 6-membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms optionally substituted by =O or =S and optionally substituted by a group of the formula ZNR?7R8; R9 and R10¿ each independently represents hydrogen, halogen, C¿1-6?alkyl, CH2OR?d¿, oxo, CO¿2R?a or CONRaRb; p is zero or 1; q is 1 or 2; and X represents -CH¿2?- or -CH2CH2-; Y represents -CH=, -CH2-, -CH2CH= or -CH2CH2-, with the proviso that the sum total of carbon atoms in X+Y is 2 or 3; and when X is -CH2- and Y is -CH= or -CH2CH=, the broken line represents a double bond; or a pharmaceutically acceptable salt thereof, are tachykinin receptor antagonists of use, for example, in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.