文献类型：期刊文献

英文题名：Discovery of novel 4-arylamino-quinazoline derivatives as EGFRL858R/T790M inhibitors with the potential to inhibit the non-small cell lung cancers

作者：Gan, Wenhui[1];Wang, Caolin[1,2,3];Pan, Qingshan[1];Li, Yuzhen[1];Guo, Yuping[1];Fan, Dang[1];Peng, Yuting[1];Rao, Zixuan[1];Xu, Shan[1];Zheng, Pengwu[1];Zhu, Wufu[1,3]

机构：[1]Jiangxi Sci & Technol Normal Univ, Sch Pharm, Jiangxi Prov Key Lab Drug Design & Evaluat, 605 Fenglin Rd, Nanchang 330013, Jiangxi, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[3]Jiangxi Sci & Technol Normal Univ, Sch Pharm, Jiangxi Prov Key Lab Drug Design & Evaluat, 605 Fenglin Rd, Nanchang 330013, Jiangxi, Peoples R China

年份：2022

卷号：127

外文期刊名：BIOORGANIC CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000826737200003)】；

基金：We gratefully acknowledge the generous support provided by National Natural Science Foundation of China (82160659) , Natural Science Foundation of Jiangxi, China (20202BABL216076, 20192BAB215061) , Practical Innovation Training Program for College Students in Jiangxi Province, China (20211504112) , Youth Top Talent Support Program of Jiangxi Science & Technology Normal University (2019QNBJRC008) , Nanchang Key Laboratory of Molecular Targeted Anticancer Drug Design and Evaluation (2019-NCZDSY-007) .

语种：英文

外文关键词：Quinazoline derivatives; NSCLC; EGFRL(858R/T790M); EGFR inhibitors

摘要：Three series of quinazoline derivatives (7a-j, 8a-o, 9a-l) were designed and synthesized as EGFRL858R/T790M inhibitors. Series 7a-j and 8a-o are urea and thiourea derivatives while category 9a-l contain the Michael re-ceptor active warhead. Most of the compounds exhibited excellent anti-proliferative activity in vitro against several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines A549 and H1975, among which 14 compounds had strong antiproliferative activity against A549 and H1975 cancer cells. What's more, they also showed moderate to excellent kinase inhibitory activity against EGFR(WT) and EGFRL(858R/T790M). 8o exhibited the best kinase inhibitory activity with IC(50 )values of 0.8, 2.7 nM against EGFR(WT) and EGFRL(858R/T790M), respectively. Moreover, AO single staining and Annexin V-FITC/PI staining results also indicated that both 8o and 9b significantly induced apoptosis in A549 cells. 8o arrested the cell cycle at S phase and 9b arrested the cell cycle at G1 phase.