Davood Asghar, Nematollahi Ali Reza, Iman Maryam, Shafiee Abbas
Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
Arch Pharm Res. 2009 Apr;32(4):481-7. doi: 10.1007/s12272-009-1401-0. Epub 2009 Apr 29.
1,4-Dihydropyridines have been recognized as calcium channel agonist. Three new analogues of Bay K8644 in which the ortho trifluromethyl phenyl group at position 4 is replaced by the 4-(5)-Chloro-2-ethyl-5-(4)-imidazolyl substituent, were designed and synthesized as calcium channel agonist. For this propose, the structures of designed compounds were drawn by HYPERCHEM program. Conformations of the compounds were optimized through semi-empirical method followed by PM3 calculation. Then the crystalin stucture of L-type calcium channel was obtained from the Protein Data Bank (PDB) server. Docking calculations were carried out using Auto-Dock.4 program. The good interaction of our 1,4-DHP derivatives showed that they can be as possible calcium channel agonist agents. Finally compounds were synthesized according to a modified Hantzsch condensation procedure.
1,4 - 二氢吡啶已被公认为钙通道激动剂。设计并合成了三种新型的Bay K8644类似物,其中4位的邻三氟甲基苯基被4 - (5) - 氯 - 2 - 乙基 - 5 - (4) - 咪唑基取代基所取代,作为钙通道激动剂。为此,通过HYPERCHEM程序绘制了设计化合物的结构。通过半经验方法并随后进行PM3计算对化合物的构象进行了优化。然后从蛋白质数据库(PDB)服务器获得L型钙通道的晶体结构。使用Auto - Dock.4程序进行对接计算。我们的1,4 - DHP衍生物的良好相互作用表明它们有可能成为钙通道激动剂。最后,根据改进的汉茨希缩合程序合成了化合物。