1,1-二苯基取代丁烯类化合物的设计合成及其对BK通道的开放活性

Design and synthesis of 1,1-diphenyl substitu ted butene derivatives and their opening activities on BK channel

目的设计合成新的大流量钙激活钾离子通道开放剂。方法以他莫希芬为先导化合物,采取分子间McMurry偶联反应合成15个新化合物,采用荧光分析法,利用高表达鼠的α和β1亚基的HEK293细胞对目标化合物进行活性筛选。结果与结论目标化合物结构经质谱、高分辨质谱及氢谱确证,与对照药他莫希芬相比,具有类似的大流量钙激活钾离子通道开放活性。

Aim To design and synthesize a new type of BK channel openers and to test their opening abilities on BK channel by fluorescence method. Methods Fifteen target compounds were designed by choosing tamoxifen as the lead compounds and were synthesized by inter-molecular McMurry coupling reaction. Preliminary assay by using the fluorescent dye method with DiBAC4（3） was applied with rat rSlo α and β1 stably expressing human embryonic kidney （HEK 293） cell lines, Result and conclusion The target compounds were synthesized and characterized by FAB-MS, high-resolution FAB-MS and ^1H-NMR. According to the dye-assay result, most of them show similar activities as tamoxifen,