Nitric oxide donating anilinopyrimidines: Synthesis and biological evaluation as EGFR inhibitors

	Nitric oxide donating anilinopyrimidines: Synthesis and biological evaluation as EGFR inhibitors
	Han, C; Huang, ZJ; Zheng, C; Wan, LD; Lai, YS; Peng, SX; Ding, K; Ji, HB; Zhang, YH
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2013
卷号	66 期号:1 页码:82-90
关键词	Nitric oxide EGFR inhibitor Anilinopyrimidine Antiproliferative activity WZ4002
通讯作者	Zhang, YH (reprint author), China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Jiangsu, Peoples R China.,ding_ke@gibh.ac.cn ; hbji@sibs.accn ; zyhtgd@163.com
英文摘要	To search for potent nitric oxide (NO) donating epidermal growth factor receptor (EGFR) inhibitors, a series of phenylsulfonylfuroxan-based anilinopyrimidines 10a-h were synthesized and biologically evaluated. Compounds 10f-h exhibited potent inhibitory activity against EGFR L858R/T790M and were as potent as WZ4002 in inhibition of H1975 cells harboring EGFR L858R/T790M. Additionally, 10h produced high levels of NO in H1975 cells but not in normal human cells, and its antiproliferative activity was diminished by hemoglobin, an NO scavenger. Furthermore, 10h inhibited EGFR activation and downstream signaling in H1975 cells. These results suggest that the strong antiproliferative activity of 10h could be attributed to the synergic effects of high levels of NO production and inhibition of EGFR and downstream signaling in the cancer cells. (C) 2013 Elsevier Masson SAS. All rights reserved.
学科主题	Pharmacology & Pharmacy
类目[WOS]	Chemistry, Medicinal
关键词[WOS]	GROWTH-FACTOR RECEPTOR ; CELL LUNG-CANCER ; ANTIHEPATOCELLULAR CARCINOMA ACTIVITY ; TYROSINE KINASE INHIBITOR ; PAN-ERBB INHIBITOR ; PHASE-II TRIAL ; DRUG-RESISTANCE ; DERIVATIVES ; GEFITINIB ; FUROXANS
收录类别	SCI
语种	英语
WOS记录号	WOS:000323628500008
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/510]
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,Huang, ZJ,Zheng, C,et al. Nitric oxide donating anilinopyrimidines: Synthesis and biological evaluation as EGFR inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2013,66(1):82-90.
APA	Han, C.,Huang, ZJ.,Zheng, C.,Wan, LD.,Lai, YS.,...&Zhang, YH.(2013).Nitric oxide donating anilinopyrimidines: Synthesis and biological evaluation as EGFR inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,66(1),82-90.
MLA	Han, C,et al."Nitric oxide donating anilinopyrimidines: Synthesis and biological evaluation as EGFR inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 66.1(2013):82-90.