BIPHENYLCARBOXAMIDES USEFUL AS 5-HT1D ANTAGONISTS

摘要

Compounds of formula (I), processes for their preparation and their use as CNS agents through 5HT1D receptor antagonism are disclosed, in which A is CONR where R is hydrogen or C1-6alkyl; B is oxygen, S(O)q where q is 0, 1 or 2, or B is NR10 where R10 is hydrogen or C¿1-6?alkyl or B is CH2 when R?7¿ and R form a group D; R1 is hydrogen, halogen, C¿1-6?alkyl, C3-6cycloalkyl, COC1-6alkyl, C1-6alkoxy, hydroxy, hydroxyC1-6alkyl, hydroxyC1-6alkoxy, C1-6alkoxyC1-6alkoxy, acyl, nitro, trifluoromethyl, cyano, SR?9, SOR9, SO¿2R9, 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, NR10CO¿2R?11, NR10CONR10R11, CR10=NOR11, CNR10=NOR11¿, where R?10 and R11¿ are independently hydrogen or C¿1-6?alkyl and a is 1 to 4 or R?1¿ is an optionally substituted 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; R?2 and R3¿ are independently hydrogen, halogen, C¿1-6?alkyl, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6alkoxy, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO2R?11, CONR12R13, NR12R13¿ where R?11, R12 and R13¿ are independently hydrogen or C¿1-6?alkyl; R?4 and R5¿ are independently hydrogen or C¿1-6?alkyl; R?6¿ is hydrogen, halogen, hydroxy, C¿1-6?alkyl or C1-6alkoxy; R?7¿ is hydrogen or together with R forms a group D where D is CR?14=CR15, CR14=CR15CR14R15 or (CR14R15)¿b where b is 2 or 3 and R?14 and R15¿ are independently hydrogen or C¿1-6?alkyl; m is 0, 1, 2, or 3; n is 1 or 2; and R?8¿ is a group of formula (i) where p, q and r are independently integers having the value 1, 2 or 3; or R8 is a group of formula (ii) where s is 0, 1, 2 or 3 and R16 is hydrogen or C¿1-6?alkyl.