【摘要】 对Ｔｏｐｌｉｓ寻搜法加以改进合成５个化合物，找到６氨基１，２双（对氯苯）己烯１化合物氨基上不同取代基的“合成终点”。用分子图形学的方法对其结构与活性的关系进行研究，结果表明药物的亲脂部分处于ＣａＭ活性部位的疏水“口袋”中，而亲水部分处于“口袋”的外部，氨基上的取代基对于药物与ＣａＭ的结合影响不大。更多还原

【Abstract】 The “end of synthesis” of 6 substituted amino 1,2 bis( p chlorophenyl) hex 1 enes was found by only synthesizing five compounds according to modified Topliss operation scheme in side chain. The derivatives with hydrogen, methyl, ethyl, isopropyl and cyclopentyl groups were synthesized. The compound substituted with ethyl group showed the most potent activity in inhibiting calmodulin. The result of molecular modeling indicated that the hydrophobic part of the inhibitor is located in the hydrophobic pocket of the active site of calmodulin, and the hydrophilic part is outside the pocket. The amino substituent does not obviously affect the interaction of inhibitor and calmodulin.更多还原