N-取代苯甲酰胺类衍生物的合成与抗肿瘤活性  

Synthesis and anti-tumor activities of N-substituted benzamide derivatives

作　　者：冯娟[1] 解鹏[1] 翁志洁[1] 闫征[2] 王楠[2] 李建其[1] 

机构地区：[1]上海医药工业研究院,上海200040 [2]中国医学科学院、北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2009年第6期603-608,共6页Acta Pharmaceutica Sinica

摘　　要：为寻找新型具有抗肿瘤活性的组蛋白去乙酰化酶(HDACs)抑制剂,合成了HDACs抑制剂MS-275,并以其为先导结构设计合成了11个N-取代苯甲酰胺类目标化合物,测定体外抗肿瘤及抑酶活性。MS-275及目标化合物的结构经1HNMR及HR-MS分析确证。体外抑HDAC活性研究表明,化合物9d的抑酶活性与阳性对照药MS-275相当,值得进一步深入研究;化合物5c、5d和9c表现出明显量效关系,具有一定抑酶活性。在对各细胞株的体外抗增殖作用研究中,发现除9e外,其他10个化合物显示了对Hut78的不同抑制活性,并表现出对Hut78细胞株具有一定的选择性。To explore novel histone deacetylase （HDACs） inhibitors with anti-tumor activity, MS-275, a HDACs inhibitor, was prepared and used as a lead compound to design new N-substituted benzamide derivatives. MS-275 and eleven target compounds were obtained, and their structures were confirmed by ^1H NMR and HR-MS individually. The results showed that the activity of compound 9d was equal to MS-275 in HDACs inhibition tests in vitro and worthy of further investigation. Compound 5c, 5d and 9c displayed obvious dose-effect relationship, which possessed moderate HDACs inhibitory activities. Ten compounds except 9c had selective inhibitory activities on Hut78.

关 键 词：组蛋白去乙酰化酶 N-取代苯甲酰胺类化合物 合成 抗肿瘤活性 

分 类 号：R916[医药卫生—药学]