EP1019410A1 — Spiro-piperidine derivatives and their use as tachykinin antagonists

USPTO Abstract

The present invention relates to compounds of formula (I), wherein R1 represents halogen, hydroxy, C¿1-6?alkyl group optionally substituted by one to three fluorine atoms, C1-6alkoxy group optionally substituted by one to three fluorine atoms, or C1-6alkylthio optionally substituted by one to three fluorine atoms; R?2¿ 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; R?4, R5, R9 and R10¿ are a variety of substituents; R6 represents hydrogen, CORa, CO2Ra, COCONRaRb, COCO¿2R?a, C1-6alkyl optionally substituted by a group selected from (CO2R?a, CONRaRb¿, hydroxy, CN, COR?a, NRaRb¿, C(NOH)NRaRb, CONHphenyl(C¿1-4?alkyl), COCO2R?a¿, CONHNRaRb, C(S)NR?aRb, CONRaC¿1-6alkylR?12, CONR13C¿2-6alkenyl, CONR13C2-6alkynyl, COCONR?aRb, CONRaC(NRb)NRaRb, CONRa¿heteroaryl, and optionally substituted phenyl) or -CH¿2?C CCH2NR?7R8¿ or C¿1-6?alkyl, optionally substituted by oxo, substituted by an optionally substituted 5-membered or 6-membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms; m is 0-3 and n is 0-3, with the proviso that the sum total of m+n is 2 or 3; p is zero or 1; q is 1 or 2; and when m is 1 and n is 1 or 2, the broken line represents an optional double bond; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.