新型二氢吡啶类钙拮抗剂化合物的合成与生物活性有机化学.pdfVIP

2010 年第 30 卷 有 机 化 学 Vol. 30, 2010 第 7 期, 997～1004 Chinese Journal of Organic Chemistry No. 7, 997～1004 ·研究论文· 新型二氢吡啶类钙拮抗剂化合物的合成与生物活性 陈国华*,a 王 丽a 姚秀梅a 张明亮a 吴斐华b (a 中国药科大学药物化学教研室 南京 210009) (b 中国药科大学中药药理教研室 南京 210009) 摘要 以 1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸单甲酯(1)或双乙烯酮为原料, 设计合成了 16 个未见文献 报道的二氢吡啶类钙拮抗剂化合物 4a～4l 及 9a～9d, 利用 IR, 1H NMR, ESI-MS 和元素分析对目标化合物的结构进行 表征. 离体大鼠胸主动脉血管环收缩实验表明, 化合物 4e, 4g～4j 对 KCl 所致的血管环收缩有明显的舒张作用, 其生物 活性均强于阳性对照苯磺酸左旋氨氯地平. 关键词 二氢吡啶类钙拮抗剂; 合成; 生物活性 Synthesis and Biological Activity of Dihydropyridine Calcium Antagonists Chen, Guohua*,a Wang, Lia Yao, Xiumeia Zhang, Minglianga Wu, Feihuab a ( Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009) (b Department of Pharmacology for Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009) Abstract Sixteen new dihydropyridine calcium antagonists 4a～4l and 9a～9d were designed and synthe- sized based on 5-(methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 1 (1) or diketene. The structures of the target compounds were confirmed by IR, H NMR, ESI-MS techniques and elemental analysis. The results of preliminary pharmacological test showed that compounds 4e, 4g, 4h, 4i and 4j had obvious relaxation effect on the contraction of vascular ring of aorta induced by KCl, which were better than positive con