Design, synthesis and biological activity evaluation of three types of kinase inhibitors with nitrogen-containing skeletons

Abstract

蛋白激酶是人类生命活动中重要的信号传递使者,小分子蛋白激酶抑制剂是以蛋白激酶信号通路功能为基础,结合蛋白激酶结构进行设计合成的小分子药物。自2001年,第一个激酶抑制剂类药物Imatinib获得FDA批准,成为本领域发展的里程碑后,小分子激酶抑制剂发展迅速,大量的小分子激酶抑制剂类化合物进入临床使用。在众多蛋白激酶中,RET融合基因被鉴定为NSCLC(非小细胞性肺癌)亚型中的新致癌基因,即RET重排的存在与肺腺癌亚型相关,所以开发针对RET激酶的抑制剂有望用于相关非小细胞肺癌的治疗。 本论文以三类含氮双环母核为基础,以KQF-04-013-01为先导化合物(leadcompound),辅助以...Protein kinase is an important signaling messenger in human life. Small molecule protein kinase inhibitor can be designed on the basis of protein kinase structure. In 2001, Imatinib was the first kinase inhibitor, approved by FDA, serving as a milestone in the field of targeted cancer theraphy. Until now, 32 small molecule kinase inhibitors have been approved by FDA and achieved great success in c...学位:理学硕士院系专业:生命科学学院_生物化学与分子生物学学号:2162014115257

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