Synthesis of 11-phenyl-2,3,4,5-tetrahydro-1H-(1,4)diazepino(1,2-a)indoles and 1-(3-aminopropyl)-2-hydroxymethyl-3-phenylindoles as 5-hydroxytryptamine antagonists.
A series of novel 11-phenyl-2,3,4,5-tetrahydro-1H-(1,4)diazepino(1,2-a) indoles (5a-f) and 1-(3-aminopropyl)-2-hydroxymethyl-3-phenylindoles (6a-f) are reported. The compounds (5a-f) were prepared by the lithium aluminum hydride (LAH) reduction of corresponding 11-phenyl-1H-1-oxo-2,3,4,5-tetrahydro(1,4)diazepino(1,2-a)indoles (4a-f). The precursors (4a-f) were, in turn, prepared by the catalytic reduction of 1-(2-cyanoethyl)-3-phenylindole-2-carboxylates (2a-f) and cyclization of the resulting 1-(3-aminopropyl)-3-phenylindole-2-carboxylates (3a-f) with sodium hydride in xylene. The LAH reduction of 2a-f gave exclusively 1-(3-aminopropyl)-2-hydroxymethyl-3-phenylindoles (6a-f) and not the diazepinoindoles (5a-f) which were expected. The title compounds and the intermediates have been screened for their anti-5-hydroxytryptamine (anti-5-HT) activity. The most potent anti-5-HT compounds of this series, 6a and 6e, were found to be weak compared with cyproheptadiene, a standard anti-5-HT drug.
Rajur
S B
SB
Department of Chemistry, Karnatak University, Dharwad, India.
Merwade
A Y
AY
Basanagoudar
L D
LD
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D012702:Serotonin Antagonists / Q000138:chemical synthesis*
D001381:Azepines; D007211:Indoles; D012702:Serotonin Antagonists