BIPHENYL(THIO)AMIDE AND BIPHENYLETHAN(THI)ONE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS 5-HT1D RECEPTOR ANTAGONISTS

摘要

The invention relates to novel heterocyclic compounds of formula (I) or a salt or N-oxide thereof, in which R is a group of formulae (i), (ii) or (iii), where R1 is hydrogen, halogen, C¿1-6?alkyl, C3-6cycloalkyl, COC1-6alkyl, C1-6alkoxy, hydroxy, hydroxyC1-6alkyl, hydroxyC1-6alkoxy, C1-6alkoxyC1-6alkoxy, acyle, nitro, trifluoromethyl, cyano, SR?9, SOR9, SO¿2R?9, NR9CONR10R11, NR10SO¿2R11, SO2NR?10R11, CO¿2R?10, CONR10R11, CO¿2NR?10R11, CONR10(CH¿2)aCO2R11, (CH2)aNR?10R11, (CH¿2)aCONR?10R11, (CH¿2)aNR?10COR11, (CH¿2)aCO2C1-6alkyl, CO2(CH2)aOR?10, NR10R11, N=CNR9NR10R11, NR10CO(CH¿2)aNR?10R11, NR10CO¿2R11, CONHNR?10R11, CR10=NOR11, CNR10=NOR11¿, where R?9, R10 and R11¿ are independently hydrogen or C¿1-6?alkyl and a is 1 to 4; or R?1¿ is a group -X-R12 where R12 is an optionally substituted 5- to 7-membered heterocyclic ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulphur and X is a bond, O, S, CH¿2?, C=O, NR?13¿CO or NR13 where R13 is hydrogen or C¿1-6?alkyl; R?4 and R5¿ are independently hydrogen, halogen, C¿1-6?alkyl, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6alkoxy, hydroxyC1-6alkyl, C1-6alkylOC1-6alkyl, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO2R?10, CONR10R11, NR10R11¿ where R?10 and R11¿ are independently hydrogen or C¿1-6?alkyl, or R?4 and R5¿ together form a group -(CH¿2?)r-R?14-(CH¿2)s- where R14 is O, S, CH¿2? or NR?15¿ where R15 is hydrogen or C¿1-6?alkyl and r and s are independently 0, 1 or 2; R?2¿ is hydrogen, C¿1-6?alkyl, optionally substituted aryl or optionally substituted heteroaryl; R?3¿ is hydrogen or C¿1-6?alkyl or together with R?8¿ forms a group (CH¿2?)q where q is 2, 3 or 4; Z is oxygen or sulphur; p is 1 or 2; P is an optionally substituted bicyclic ring optionally containing one to four heteroatoms; or P is an optionally substituted 5- to 7-membered saturated or partially saturated ring optionally containing one to three heteroatoms; and B is oxygen or sulphur; D is nitrogen, carbon or a CH group; R?6¿ is hydrogen or C¿1-6?alkyl and R?7¿ is C¿1-6?alkyl, C1-6alkoxy or halogen, or R?6¿ together with R7 forms a group -A- where A is (CR16R17)t where t is 1, 2 or 3 and R?16 and R17¿ are independently hydrogen or C¿1-6?alkyl or A is (CR?16R17)¿u-J where u is 0, 1 or 2 and J is oxygen, sulphur, CR?16=CR17, CR16=N, CR16NR17¿ or N=N; R?18 and R19¿ are independently hydrogen or C¿1-6?alkyl; R?20 and R21¿ are independently hydrogen, C¿1-6?alkyl, aralkyl, or together with the nitrogen atom to which they are attached form an optionally substituted 5- to 7-membered heterocyclic ring containing one or two heteroatoms selected from oxygen, nitrogen or sulphur; m is 0 to 4; and Q is an optionally substituted 5- to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur, processes for their preparation, and their use as 5-HT1D receptor antagonists.