Hosseini Maryam, Miri Ramin, Amini Mohsen, Mirkhani Hossein, Hemmateenejad Bahram, Ghodsi Shahram, Alipour Eskandar, Shafiee Abbas
Faculty of Chemistry, Islamic Azad University, North Tehran Branch, Tehran, Iran.
Arch Pharm (Weinheim). 2007 Oct;340(10):549-56. doi: 10.1002/ardp.200600211.
A group of dialkyl and diarylester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 was replaced by a 1-methyl-4,5-dichloroimidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the high K(+)concentration of guinea-pig ileum longitudinal smooth muscle. The structure of all compounds was confirmed by IR,(1)H-NMR, and mass spectra. The calcium-channel antagonist activity of compounds 10a-f demonstrated that compound 10b was the most active and 10f the least active one. With unsymmetrical diesters 12a-k, the most active compound was the ethyl, phenethyl derivative. Structural parameters on the calcium-channel antagonist activity were evaluated by QSAR analysis and a linear correlation was found between the -log IC(50) values of these compounds and their constitutional and topological properties.
合成了一组硝苯地平的二烷基和二芳基酯类似物，其中4位的邻硝基苯基被1-甲基-4,5-二氯咪唑基取代基取代，并使用豚鼠回肠纵行平滑肌的高钾浓度作为钙通道拮抗剂进行了评估。所有化合物的结构均通过红外光谱、¹H-NMR和质谱得到证实。化合物10a-f的钙通道拮抗剂活性表明，化合物10b活性最高，10f活性最低。对于不对称二酯12a-k，活性最高的化合物是乙基苯乙基衍生物。通过定量构效关系（QSAR）分析评估了钙通道拮抗剂活性的结构参数，发现这些化合物的-log IC₅₀值与其结构和拓扑性质之间存在线性相关性。
