EP0741704A1 — Aralkylamino substituted azacyclic therapeutic agents

USPTO Abstract

The present invention relates to compounds of formula (I) wherein n is 1, 2 or 3 and where any carbon atom of (CH2)n may be substituted by R4 and/or R5; R1 represents (CH¿2?)qphenyl, wherein q is zero, 1, 2 or 3, which may be optionally substituted in the phenyl ring; R?2¿ represents aryl selected from phenyl and naphthyl; heteroaryl selected from indazolyl, thienyl, furyl, pyridyl, thiazolyl, tetrazolyl and quinolyl; benzhydryl; or benzyl; wherein each aryl or heteroaryl moiety may be substituted; R3 represents H or C¿1-6?alkyl; R?4 and R5¿ each independently represent H, halo, C¿1-6?alkyl, oxo, CO2R?a¿ or CONRaRb; R6 represents H or C¿1-6?alkyl; R?7¿ represents H, C¿1-6?alkyl optionally substituted by a hydroxy group, or (CH2)pNR?9R10, CO¿2R?16, CONR9R10, (CH¿2)pCO2R16, (CH2)pCONR?9R10, (CH¿2)pNR?9COR16, (CH¿2)pNHSO2R11, (CH2)pOR16, (CH2)pOC(O)R9, (CH2)pOC1-4alkylCOR17, or optionally substituted phenyl; R8 represents H, CORa, CO2Ra, COCONRaRb, COCO¿2R?a, C1-6alkyl optionally substituted by a group selected from (CO2R?a, CONRaRb¿, hydroxy, cyano, COR?a, NRaRb¿, C(NOH)NRaRb, CONHphenyl(C¿1-4?alkyl), COCO2R?a¿, CONHNRaRb, C(S)NR?aRb, CONRaC¿1-6alkylR?12, CONR13C¿2-6alkynyl, CONR13C2-6alkenyl, COCONR?aRb, CONRaC(NRb)NRaRb, CONRa¿heteroaryl, and optionally substituted phenyl) or C¿1-6?alkyl, optionally substituted by oxo, substituted by an optionally substituted aromatic heterocycle; with the proviso that when R?6 and R7¿ both represent H, R8 represents C¿1-6?alkyl optionally substituted by oxo, substituted by an optionally substituted aromatic heterocycle selected from pyrrolyl, pyrazolyl, pyrazinyl, pyridazinyl, oxadiazolyl, thiadiazolyl, imidazolyl, benzimidazolyl, benzoxazolyl, benzthiophenyl, benzofuranyl and indolyl, or a substituted aromatic heterocycle selected from thienyl, furyl, pyridyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, quinolyl, isoxazolyl and isothiazolyl; and R?a and Rb¿ each independently represent H, C¿1-6?alkyl, trifluoromethyl or phenyl optionally substituted by C1-6alkyl, halo or trifluoromethyl. The compounds are of particular use in the treatment of pain, inflammation, migraine and emesis.