5-SUBSTITUTED-3-(1,2,3,6-TETRAHYDROPYRIDIN-4-YL)- AND 3-(PIPERIDIN-4-YL)-1H-INDOLES; PREPARATION AND MEDICAMENTS

摘要

This invention provides novel 5-HT1F agonists which are useful for the treatment of migraine and associated disorders. The compounds have the formula in which A-B is -CH-CH2- or -C=CH-; R is H or C1-C6 alkyl; R<1> is H or C1-C4 alkyl; X is -S-R<2>, -C(O)R<3>, -C(O)NR<4>R<15>, -NR<5>R<6>, -NR<7>SO2R<8>, -NHC(Q)NR<10>R<11>, -NHC(O)OR<12> or -NR<13>C(O)R<14>; where Q is O, or S; R<2> is phenyl, substituted phenyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, or pyridinyl; R<3> is C1-C6 alkyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, naphthyl, N-methyl-N-methoxyamino, heteroaryl, substituted heteroaryl, heteroaryl(C1-C4 alkyl), or substituted heteroaryl(C1-C4 alkyl); R<4> is heteroaryl, substituted heteroaryl, heteroaryl(C1-C4 alkyl), or substituted heteroaryl(C1-C4 alkyl); R<4> and R<15> taken together with the nitrogen atom form a pyrrolidine, piperidine, substituted piperidine, piperazine, 4-substituted piperazine, morpholine or thiomorpholine ring; R<5> and R<6> are both trifluoromethanesulfonyl; R<7> is H or C1-C4 alkyl; R<8> is C1-C4 alkyl, phenyl, substituted phenyl, or di(C1-C4 alkyl)amino; R<10> and R<11> are independently selected from the group consisting of C1-C6 alkyl, C3-C6 alkenyl, C3-C8 cycloalkyl, phenyl, substituted phenyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted in the phenyl ring, ((C1-C4 alkyl or C1-C4 alkoxycarbonyl substituted)C1-C4 alkyl)phenyl, C1-C4 alkyl alpha -substituted with C1-C4 alkoxycarbonyl; or R<10> and R<11> taken together with the nitrogen atom form a pyrrolidine, piperidine, piperazine, 4-substituted piperazine, morpholine or thiomorpholine ring; R<12> is C1-C6 alkyl, C3-C6 alkenyl, phenyl, substituted phenyl, C3-C8 cycloalkyl, C1-C4 alkyl omega -substituted with C1-C4 alkoxy; R<13> is H or C1-C4 alkyl; R<14> is C1-C10 alkyl substituted with up to three substituents selected from the group consisting of hydroxy, C1-C4 alkoxy, halo, aryloxy, C1-C4 alkoxycarbonyl and heteroaryloxy, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, phenyl, substituted phenyl, naphthyl, phenyl(C1-C4 alkylene), phenyl(C1-C4 alkylene) substituted on the phenyl ring, 2-phenylethylen-1-yl, diphenylmethyl, benzofused C4-C8 cycloalkyl, C1-C4 alkylene omega -substituted with C3-C6 cycloalkyl, or a heterocycle; R<15> is H or C1-C6 alkyl; subject to the proviso that when R<7> is H, R<8> is not C1-C4 alkyl; and pharmaceutically acceptable acid addition salts and solvates thereof.