Department of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Reg, Russia.
Bioorg Med Chem Lett. 2010 Jan 1;20(1):78-82. doi: 10.1016/j.bmcl.2009.11.037. Epub 2009 Nov 14.
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)4(3)>>dimebolin, all of them having highest affinities to 5-HT(7) receptors.
本文报道了一系列新型 5-取代乙烯基和 5-取代苯乙基二美辛啉类似物的合成、生物评价和构效关系。这些新型衍生物与二美辛啉具有广泛的针对治疗相关靶点的活性。在所有合成的衍生物中，2,8-二甲基-5-[(Z)-2-苯基乙烯基]-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚及其 5-苯乙基类似物是 5-HT(7)、5-HT(6)、5-HT(2C)、肾上腺素能α(2)和 H(1)受体的最强阻断剂。它们对研究受体的一般亲和力顺序为 Z-3(2)>4(2)4(3)>二美辛啉，所有这些化合物对 5-HT(7)受体都具有最高的亲和力。
