期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 140, 期 -, 页码 212-228出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.08.060
关键词
c-Met; tyrosine kinase; Diazepine derivatives; Synthesis; Antitumor
资金
- National Natural Science Foundation of China [81273373]
- Science and Technology Commission of Shanghai Municipality [12431901101, 14YF1412800]
Over expression of c-Met tyrosine kinase is known to promote tumorigenesis and metastasis, as well as to cause therapeutic resistance. Herein a series of novel 6,11-dihydro-5H-benzo[e]pyrimido[5,4-b][1,4] diazepine derivatives were designed, synthesised and evaluated for their c-Met kinase inhibition. Compounds 17e, 17f, 18a, and 18b were further examined for their anti-proliferative activities against four typical cancer cell lines (PC-3, Panc-1, HepG2, and Caki-1). The promising compound 17f was identified as a multi-target receptor tyrosine kinase inhibitor, which also displayed favourable pharmacokinetic properties in rats, had an acceptable safety profile in preclinical studies, and significant anti tumour activity in the Caki-1 tumour xenograft model. (C) 2017 Published by Elsevier Masson SAS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据