Design, synthesis and anti-tumor activity of N-Phenyl-2-(4-phenyl)-cyclo-propane-1-carboxylic acid-1-amide
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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。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.
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Key words:
- cyclopropyl-amide /
- anti-tumor activity /
- structure-activity relationships
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[1] 王甜甜, 李科. 四氢呋喃木脂素、四氢呋喃并[3,4-c]吡喃-4-酮、2,5-二氢呋喃以及呋喃衍生物的设计、合成和抗肿瘤活性研究[D]. 第二军医大学博士论文, 2011. [2] 姜殿君, 赵丽妮, 崔晶. 抗肿瘤药物治疗的研究进展[J]. 中国现代医药杂志, 2009, 11(4):8. [3] 周大铮, 易杨华, 毛士龙. 香榧假种皮中的木脂素成分[J]. 药学学报, 2004, 39(4):269. [4] 周大铮, 易杨华. 香榧中抗艾滋病病毒活性先导化合物的研究和结构修饰[D]. 第二军医大学博士论文, 2004. [5] Wang TT, Liu J, Li K, et al. Efficient and mild synthesis of highly substituted 2,5-dihydrofuran and furan derivatves via stepwise reaction[J]. Tetrahedron,2011, 67(7):3476. [6] Sun HL, Wang TT, Li K, et al. Synthesis, chiral resolution, and determination of novel furan lignan derivatives with potent anti-tumor activity[J]. Bioorg Med Chem Lett, 2010, 20(11):1961. [7] Wang TT, Liu J, Li K, et al. Synthesis and anti-tumor activity of novel ethyl 3-aryl-4-oxo-3, 3a, 4, 6-tetrahydro-1H-furo[3, 4-c] pyran-3a-carboxylates[J]. Bioorg Med Chem Lett, 2011, 21(9):3381. [8] He XR, Qiu GP, Yang J, et al. Synthesis and anticonvulsant activity of new 6-methyl-1-substituted-4, 6-diazaspiro[2.4] heptane-5, 7-diones[J]. Eur J Med Chem, 2010, 45(6):3818. -
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