新型氮杂多肽酰肼类衍生物的设计、合成和抗肿瘤活性研究

目的:新型氮杂多肽酰肼类衍生物的设计和合成及其抗肿瘤活性研究。方法:以脯氨酸甲酯盐酸盐为原料,通过与苄氧羰基丙氨酸反应,在肼中肼解,得到所需中间体,进而与富马酸单酯反应得到目标化合物;和溴乙酸叔丁酯反应,三氟乙酸中脱去叔丁氧基,再与取代胺或氨水反应得到目标化合物。用MTT法测试合成的氮杂多肽酰肼类衍生物对肿瘤细胞的抑制活性。结果:合成了10个氮杂多肽酰肼类衍生物,其中有6个化合物对肿瘤细胞表现出抑制活性。结论:初步建立了氮杂多肽酰肼类衍生物的合成方法及其对肿瘤细胞抑制活性的构效关系。

Design, Synthesis and Antitumor Research of Aza-Peptide Michael Acceptors

Objective:To design and synthesize new Aza-Peptide Michael Acceptor derivatives and antitumor activity study.Methods:L-Prolinemethylesterhydrochloride was applied as starting material, reacting with Cba-AlaOH, then the intermediate was obtained under a hydrazinolysis proce- dure, which reacted with fumaric acid mono ester to give the designed compounds, or reacted with BrCH2COOtBu and fumaric acid mono ester successively. After deprotection in TFA, the acid was coupled to a series of amines to give the final products.Results:10 new Aza-Peptide Michael Acceptor derivatives were prepared and 6 compounds among them exhibited antitumor activity.Conclusion:Synthetic method and preliminary SAR has been built for the new Aza-Peptide Michael Acceptor derivatives against tumor cell lines.