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-HT(7), 5-HT(6), 5-HT(2C), Adrenergic alpha(2) and H(1) receptors. The general affinity rank order towards the studied receptors was Z-3(2) >= 4(2) P4(3) >> dimebolin, all of them having highest affinities to 5-HT7 receptors. (C) 2009 Elsevier Ltd. All rights reserved.