N-取代苯基-2-(4-取代苯基)环丙烷-1-甲酸乙酯-1-酰胺的设计、合成及抗肿瘤活性
投稿时间:2012-04-16  最后修改时间:2012-06-08  点此下载全文
引用本文:陈焕,耿冬平,李科.N-取代苯基-2-(4-取代苯基)环丙烷-1-甲酸乙酯-1-酰胺的设计、合成及抗肿瘤活性[J].药学实践杂志,2012,30(6):422~426,461
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作者单位E-mail
陈焕 第二军医大学药学院药物化学教研室, 上海 200433  
耿冬平 第二军医大学药学院药物化学教研室, 上海 200433  
李科 第二军医大学药学院药物化学教研室, 上海 200433 proflike@sina.com 
基金项目:国家自然基金(21172259).
中文摘要:目的 设计、合成N-取代苯基-2-(4-取代苯基)环丙烷-1-甲酸乙酯-1-酰胺类化合物,并进行抗肿瘤活性研究。方法 采用微波反应,经缩合、环化、水解以及酰胺化等反应合成目标化合物。所合成化合物经1H NMR谱图和质谱进行确证,并对其进行体外抗肿瘤活性筛选。结果 设计、合成了20个环丙烷酰胺类化合物。体外药理活性实验显示,所合成的目标化合物具有较好的抗肿瘤活性,其中5b对A549细胞的IC50值为6.8 μM, 具有进一步研究的价值。结论 对氯苯基取代化合物比对三氟甲基苯基取代化合物有更好的抗肿瘤活性;酰胺芳香环吸电子基团化合物活性优于供电子基团化合物。
中文关键词:环丙烷酰胺  抗肿瘤活性  构效关系
 
Design, synthesis and anti-tumor activity of N-Phenyl-2-(4-phenyl)-cyclo-propane-1-carboxylic acid-1-amide
Abstract:Objective To design, synthesize and study the anti-tumor activity in vitro of N-Phenyl-2-(4-phenyl)-cyclopropane-1-carboxylic acid-1-amide compounds. Methods The target compounds were obtained through knoevenagel condensation, cyclization, hydrolysis and amidation reaction, microwave reaction equipment contributed to improve efficiency. Structure of the target compounds were determined by 1H NMR and LC-MS.Results Design, synthesis of 20 novel cyclopropyl-amide compounds and anti-tumor assay showed all of the target compounds had significant anticancer activity in vitro. Compound 5b had the best activity in A549 cell with IC50 6.8 μM. Conclusion 4-trifluoromethyl substituted phenyl compounds had better anticancer activity than 4-chlorine substituted phenyl compounds.Electron-withdrawing group made more contributed than electron-donating group for anticancer activity in vitro.
keywords:cyclopropyl-amide  anti-tumor activity  structure-activity relationships
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