6-(4-Methyl-piperazin-1-yl)-1H-indole derivatives useful as 5HT1A, 5HT1B and 5HT1D receptor antagonists

摘要

An indole derivative of formula (I) or a salt thereof is disclosed wherein: Ra is a group of formula (i) or (ii) P1 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; R1 is hydrogen, halogen, alkyl, cycloalkyl, CO-alkyl, alkoxy, hydroxy, hydroxyalkyl, hydroxyalkoxy, alkoxyalkoxy, acyl, nitro, trifluoromethyl, cyano, SR9, SOR9, SO2R9, SO2NR10R11, CO2R10, CONR10R11, CO2NR10R11, CONR10(CH2)cCO2R11, (CH2)cNR10R11, (CH2)cCONR10R11, (CH2)cNR10COR11, (CH2)cCO2alkyl, CO2(CH2)cOR10, NR10R11, NR10CO2R11, NR10CONR10R11, CR10=NOR11, NR10COOR11 CNR10=NOR11; R10 and R11 are independently hydrogen or alkyl; c is 1 to 4; R2 is hydrogen, halogen, alkyl, cycloalkyl, cycloalkenyl, alkoxy, alkanoyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO2R10, CONR10R11, NR10R11; a is 1, 2 or 3; P2 and P3 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, carbonyl, CH2, -CH2CH2- or NR4; R4 is hydrogen or alkyl; m is 0 to 2; for formula (ii) R1 can also be an optionally substituted 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; R2 and R3 are independently hydrogen, halogen, alkyl, cycloalkyl, cycloalkenyl, alkoxy, alkanoyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO2R10, CONR10R11, NR10R11; b is 1, 2 or 3; Y is -NH-, -NR5-, -CH2- or -O-; R5 is alkyl; V is oxygen or sulphur; D is nitrogen, carbon or a CH group; W is (CR16R17)t or (CR16R17)u-J t is 2, 3 or 4; R16 and R17 are independently hydrogen or alkyl; u is 0, 1, 2 or 3; J is oxygen, sulphur, CR16=CR17, CR16=N, =CR16O, =CR16S or =CR16-NR17; X is nitrogen or carbon; Rb is hydrogen, halogen, hydroxy, alkyl, trifluoromethyl, alkoxy, alkenyl, cycloalkyl optionally substituted by alkyl, or aryl; Re is hydrogen or alkyl; the dotted line is a single bond when X is nitrogen or a single or double bond when X is carbon. A pharmaceutical composition thereof is useful for treating CNS disorders.