N-(2,3-二甲基-2H-吲唑-6-基)-2-甲基嘧啶二胺衍生物的合成及活性研究  

Synthesis and Biological Evaluation of N-(2,3-Dimethyl-2H-Indazol-6-yl)-2-Methylpyrimidinediamine Derivatives

作　　者：杨照[1] 方正[2] 王志祥[1] 郭凯[2] 

机构地区：[1]中国药科大学药学院,南京210009 [2]南京工业大学药学院,南京211816

出　　处：《中国药学杂志》2013年第21期1870-1874,共5页Chinese Pharmaceutical Journal

基　　金：国家重点基础研究发展973计划(2012CB721104);高等学校博士学科点专项科研基金(20113221120008)

摘　　要：目的合成N-(2,3-二甲基-2H-吲唑-6-基)-2-甲基嘧啶二胺衍生物,测试所合成化合物的体外抗肿瘤活性。方法在已上市的多靶点小分子抗肿瘤药pazopanib的构效关系基础上,采用基于片段的药物设计方法设计合成目标化合物;采用四氮唑盐(MTT)法测试所合成化合物的体外抗肿瘤活性。结果合成了14个N-(2,3-二甲基-2H-吲唑-6-基)-2-甲基嘧啶二胺衍生物,目标化合物的结构经1H-NMR、MS及元素分析确证。结论大多数合成的化合物表现出一定的抗肿瘤活性,其中化合物B1和B2的抗肿瘤活性优于阳性对照。OBJECTIVE To synthesize N-（2,3-dimethyl-2H-indazol-6-yl）-2-methylpyrimidinediamine derivatives and determine their antitumor activities in vitro. METHODS Basing on the marketed multi-target antitumor agent, pazopanib, the objective sub- stances were designed and synthesized according to the principle of fragment-based drug discovery. The antitumor activities in vitro of the synthesized compounds were evaluated by MTI＇ method. RESULTS Fourteen derivatives were synthesized. Their structures were identified by i H-NMR, MS and elemental analysis. CONCLUSION It is shown that most of the synthesized compounds have antitu- mor activities, among which compound B1 and B2 show better antitumor activity than the positive control.

关 键 词：嘧啶二胺 吲唑 PAZOPANIB 合成 生物活性 

分 类 号：R914.5[医药卫生—药物化学]