Synthesis and biological activity of 5-styryl and 5-phenethyl-substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles

Syntheses, biological evaluation, and structure–activity relationships for a series of novel 5-styryl and 5-phenethyl analogs of dimebolin are disclosed. The novel derivatives and dimebolin share a broad spectrum of activities against therapeutically relevant targets. Among all synthesized derivatives, 2,8-dimethyl-5-[(Z)-2-phenylvinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and its 5-phenethyl analog are the most potent blockers of 5-HT7, 5-HT6, 5-HT2C, Adrenergic α2 and H1 receptors. The general affinity rank order towards the studied receptors was Z-3(2) > 4(2) ⩾ 4(3) ≫ dimebolin, all of them having highest affinities to 5-HT7 receptors.

Graphical abstractThe syntheses, biological evaluations, and structure–activity relationships for a series of novel Z-5-styryl, E-5-styryl and 5-phenethyl analogs of 2,3,4,5-tetrahydro-1H-γ-carbolines as potent blockers of serotonin, histamine, and adrenergic receptors are disclosed.Figure optionsDownload full-size imageDownload as PowerPoint slide