N-(氨基吡啶)苯甲酰胺类衍生物的合成与抗肿瘤活性

Synthesis and anti-tumor activities of N-(aminopyridine) benzamide derivaties

为寻找具有抗肿瘤活性的新型组蛋白去乙酰化酶(HDAC)抑制剂,在前期研究发现活性结构A和B的基础上,设计合成了N-(2-氨基-4-吡啶)苯甲酰胺类(A类)化合物和N-(2-氨基-3-吡啶)苯甲酰胺类(B类)化合物各16个。32个目标化合物的结构经1HNMR及HR-MS分析确证。体外抑HDACs活性研究表明,除Ⅴ-20、Ⅴ-21外,其余30个化合物在200μmol·L-1下均表现出一定的抑酶活性。对各肿瘤细胞株的体外抗增殖作用研究表明,化合物Ⅴ-30、Ⅴ-31、Ⅴ-32对Hut78、Jurkat E6-1、A549、K562及MDA-MB-435s5种肿瘤细胞具有良好的抑制活性。

To explore novel histone deacetylase （HDAC） inhibitors with anti-tumor activity, on the basis of preliminary studies, sixteen N-（2-amino-4-pyridine） benzamide derivaties （class A） and sixteen N-（2-amino-3- pyridine） benzamide derivaties （class B） were designed and prepared, and their structures were confirmed by ^1H NMR and HR-MS individually. The results showed that 30 target compounds except V-20 and V-21 had HDACs inhibitory activity and V-13, V-14, V-16 were equal to CI-994 at 200 μmol.L^-1 in vitro. Compounds V-30, V-31 and V-32 exhibited potent inhibitory activities on Hut78, Jurkat E6-1. A549, K562 and MDA-MB-435s.