Indole derivatives having combined 5ht1a, 5ht1b and 5ht1d receptor antagonist activity

摘要

Compounds of formula (I), processes for their preparation and their use as CNS agents are disclosed, in which R is a group of formula (i), in which P<1> is phenyl, bicyclic aryl, a 5- to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur, or a bicyclic heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur; R<1> is hydrogen, halogen, C1-6alkyl, C3-6cycloalkyl, COC1-6alkyl, C1-6alkoxy, hydroxy, hydroxyC1-6alkyl, hydroxyC1-6alkoxy, C1-6alkoxyC1-6alkoxy, C1-6alkanoyl, nitro, trifluoromethyl, cyano, SR<9>, SOR<9>, SO2R<9>, SO2NR<1O>R<11>, CO2R<10>, CONR<10>R<11>, CO2NR<10>R<11>, CONR<10>(CH2)cCO2R<11>, (CH2)cNR<10>R<11>, (CH2)cCONR<10>R<11>, (CH2)cNR<10>COR<11>, (CH2)cCO2C1-6alkyl, CO2(CH2)cOR<10>, NR<10>R<11>, NR<10>CO2R<11>, NR<10>CONR<10>R<11>, CR<10>=NOR<11>, NR<10>COOR<11>, CNR<10>=NOR<11>, where R<10> and R<11> are independently hydrogen or C1-6alkyl and c is 1 to 4; R<2> is hydrogen, halogen, C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6alkoxy, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO2R<10>, CONR<10>R<11>, NR<10>R<11> where R<10> and R<11> are as defined for R<1>; a is 1, 2 or 3; or R is a group of formula (ii), wherein P<2> and P<3> are independently phenyl, bicyclic aryl, a 5- to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur, or a bicyclic heterocyclic group containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; A is a bond or oxygen, S(O)m where m is 0 to 2, carbonyl, CH2 or NR<4> where R<4> is hydrogen or C1-6alkyl; R<1> is as defined above for formula (I) 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 R<3> are independently hydrogen, halogen, C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6alkoxy, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO2R<10>, CONR<10>R<11>, NR<10>R<11> where R<10> and R<11> are as defined for R<1>; and a and b are independently 1, 2 or 3; Y is -NH-, NR<5> where R<5> is C1-6alkyl, or Y is -CH2- or -O-; V is oxygen or sulphur; D is nitrogen, carbon or a CH group; W is (CR<16>R<17>)t where t is 2, 3 or 4 and R<16> and R<17> are independently hydrogen or C1-6alkyl or W is (CR<16>R<17>)u-J where u is 0, 1, 2 or 3 and J is oxygen, sulphur, CR<16>=CR<17>, CR<16>=N, =CR<16>O, =CR<16>S or =CR<16>-NR<17>; X is nitrogen or carbon; R is hydrogen, halogen, hydroxy, C1-6alkyl, trifluoromethyl, C1-6alkoxy, C2-6alkenyl, C3-7cycloalkyl optionally substituted by C1-4alkyl, or aryl; R is hydrogen or C1-6alkyl; and ..... is a single bond when X is nitrogen or a single or double bond when X is carbon.