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以邻氨基苯甲酸、芳醛和甘氨酸乙酯为原料,利用亚胺和亚胺烯酮的加成反应,芳构化合成了系列含氨基酸链的C-2和N-3双取代的喹唑啉-4-酮衍生物5.酸性条件下脱除羧甲基,设计合成了连有氨基侧链的喹唑啉酮衍生物9,并评价了化合物的抗肿瘤细胞增殖活性.化合物9ba和9bc具有较好的抗Hela细胞增殖活性,IC_(50)值分别为8.16和7.47μmol/L,而9bc和9bd具有较好的抗A549细胞增殖活性,IC_(50)值分别为5.62和9.54μmol/L.构效关系表明,C-2位香豆素(较大的π平面芳环)取代以及氨基侧链的引入有利于化合物的抗肿瘤活性.
Using anthranilic acid, aromatic aldehyde and glycine ethyl ester as raw materials, a series of C-2 and N-3 substituted quinazolines with amino acid chains were synthesized by aromatization of imine and imine enone. 4-one derivatives 5. The carboxymethyl groups were removed under acidic conditions, and the quinazolinone derivatives with amino side chains 9 were designed and synthesized, and the anti-tumor cell proliferation activity of the compounds was evaluated. Compounds 9ba and 9bc The IC50 values were 8.16 and 7.47μmol / L, respectively. However, 9bc and 9bd had better antiproliferative activity against A549 cells with IC50 values of 5.62 and 9.54μmol / L. Structure-activity relationship shows that C-2 coumarin (larger π-plane aromatic ring) substitution and the introduction of amino side chain is conducive to the anti-tumor activity of the compound.