Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors

	Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors
	Han, C; Wan, LD; Ji, HB; Ding, K; Huang, ZJ; Lai, YS; Peng, SX; Zhang, YH
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2014
卷号	77 期号:1 页码:75-83
关键词	EGER inhibitor Nitric oxide Antiproliferadve effects 3-Aminopropamides Acrylamide Anilinopyrimidine
通讯作者	Huang, ZJ (reprint author), China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Jiangsu, Peoples R China.,cpudahuang@163.com ; lcpu333@yahoo.com.cn ; zyhtgd@163.com
英文摘要	Novel compounds 12a-i were synthesized and biologically evaluated. Several ones exhibited stronger inhibitory activity than gefitinib against EGFR L858R/T790M and antiproliferative effects on H1975 and HCC827 cells. The 3-aminopropamide in compounds like 12h could be converted to the active acrylamide in the presence of arginine. Importantly, 12h showed improved stability relative to compound 1 whose structure is same to 12h excepting an acrylamide moiety. Interestingly, 12i, a NO donating compound of 12h, showed more potent and selective inhibition than 12h on H1975 cells. Significantly, 12i produced high levels of NO in H1975 cells but not in non-tumorous 16HBE cells, and its inhibition was diminished by NO scavenger. Furthermore, 12i dose-dependently produced inhibitory effects on EGFR downstream signaling in H1975 cells. (c) 2014 Elsevier Masson SAS. All rights reserved.
学科主题	Pharmacology & Pharmacy
类目[WOS]	Chemistry, Medicinal
关键词[WOS]	CELL LUNG-CANCER ; ANTIHEPATOCELLULAR CARCINOMA ACTIVITY ; OXIDE-RELEASING DERIVATIVES ; PAN-ERBB INHIBITOR ; PHASE-II TRIAL ; NITRIC-OXIDE ; TYROSINE KINASE ; BIOLOGICAL EVALUATION ; EGFR ; RESISTANCE
收录类别	SCI
语种	英语
WOS记录号	WOS:000335874800008
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/302]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Han, C,Wan, LD,Ji, HB,et al. Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2014,77(1):75-83.
APA	Han, C.,Wan, LD.,Ji, HB.,Ding, K.,Huang, ZJ.,...&Zhang, YH.(2014).Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,77(1),75-83.
MLA	Han, C,et al."Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 77.1(2014):75-83.