苯甲酰胺类组蛋白去乙酰化酶抑制剂的合成及 抗肿瘤细胞增殖活性

目的 针对组蛋白去乙酰化酶（HDAC）的结构特点，设计合成一系列化合物并进行体外抗肿瘤活性评价，为进一步优化设计提供指导。方法 以 2-羟基-4-硝基苯甲醛为原料，经环合、还原、与芳醛衍生物反应、水解后，在N,N-碳酰二咪唑存在下经缩合反应合成目标化合物。结果与结论 共合成了11个新苯甲酰胺类衍生物，化合物的结构经质谱、核磁共振氢谱确证；体外抗肿瘤活性评价结果表明，其中 4 个化合物（4b、4c、4d、4h）对肿瘤细胞具有显著的增殖抑制活性，化合物4h的活性最好，它对 HL60、MCF-7、A549 肿瘤细胞的 IC₅₀值分别为2.81、＞50、4.79 μmol·L^-1。

Synthesis and antitumor activities of benzamide derivatives as novel histone deacetylase inhibitors

It is known that HDAC is studied as an important target in the area of tumor inhibition.As a result,it is necessary to find a kind of small molecule HDAC inhibitor.Based on the good antitumor activities of MS-275 and CI-994,eleven novel benzamide derivatives were designed and synthesized.Ethyl 6-aminobenzofuran-2-carboxylate was prepared from 2-hydroxy-4-nitro-benzaldehyde by two steps including cyclization and reduction,and it was converted to the target compounds through reductive amination,hydrolysis and...