Design, synthesis and evaluation of novel non-ATP competitive CHK1 inhibitors as chemotherapy sensitizing agents  

新型非ATP竞争型细胞周期检查点激酶1(CHK1)抑制剂的设计、合成及活性评估（英文）

作　　者：李远新[1] 韩子飞 田超[1] 张志丽[1] 刘俊义[1] 

机构地区：[1]北京大学医学部药学院化学生物学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2016年第10期726-736,共11页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.21302007)

摘　　要：A series of urea-based compounds containing purine moieties were designed and synthesized as novel non-ATP competitive CHK1 inhibitors. The biological evaluation showed that several target compounds exhibited more potent inhibitory effects against CHK1 than the lead compound. In addition, one particular compound displayed synergistic effects with gemcitabine against HT29 cells.本文根据已报道的非ATP竞争型CHK1抑制剂,设计并合成了分别具有吡咯并嘧啶和嘌呤结构的两类脲类化合物作为新型非ATP竞争型CHK1抑制剂,并进行了初步的生物活性测试。结果显示,大部分化合物尤其是嘌呤系列化合物17f不仅对CHK1的抑制活性高于先导化合物,而且展现出一定的抗肿瘤增强作用。

关 键 词：CHK1 inhibitors Non-ATP competitive Anti-cancer synergistic effect 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]