Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y(1) receptor antagonists

doi:10.1016/j.ejmech.2018.09.014

	Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y(1) receptor antagonists
	Peng, Jingjing 2,3; Zhao, Lifen 2; Wang, Lanlan 1; Chen, Hui 2,3; Qiu, Yunguang 2,3; Wang, Jiang2,3 ; Yang, Huaiyu 4; Liu, Jun 1; Liu, Hong2,3
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2018-10-05
卷号	158 页码:302-310
关键词	P2Y(1) receptor antagonist 2-(phenoxyaryl)-3-urea derivatives Anti-Platelet
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2018.09.014
文献子类	Article
英文摘要	A novel series of 2-(phenoxyaryl)-3-urea derivatives were designed, synthesized, and biologically evaluated for their anti-thrombotic activity. Most of compounds exhibited good inhibition against P2Y(1) receptor. Among them, three compounds 11, 12, and 13 demonstrated good P2Y(1) receptor antagonistic potency in vitro (IC50 = 0.62 mu M, 0.82 mu M, and 0.21 mu M, respectively). In antiplatelet aggregation study, four compounds 2, 3, 9, and 13 showed good antiplatelet activity. The possible binding modes of compounds with P2Y(1) receptor were also explored by molecular docking simulation. The docking studies demonstrated that compound 13 interacted well with Phe119 through hydrophobic interaction and modestly improved the P2Y(1) receptor antagonistic activity, making it justifiable for further investigation. (C) 2018 Published by Elsevier Masson SAS.
资助项目	National Natural Science Foundation of China[81620108027] ; National Natural Science Foundation of China[21632008] ; National Natural Science Foundation of China[21672231] ; National Natural Science Foundation of China[21472209] ; Major Project of Chinese National Programs for Fundamental Research and Development[2015CB910304]
WOS关键词	PLATELET-AGGREGATION ; ANTIPLATELET AGENTS ; HIGH-AFFINITY ; DIARYL UREAS ; THROMBOSIS ; DISCOVERY ; POTENT ; MICE ; PHARMACOKINETICS ; CLOPIDOGREL
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000448094000022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279537]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Jun; Liu, Hong
作者单位	1.China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing 210009, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 4.East China Normal Univ, Sch Life Sci, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China
推荐引用方式 GB/T 7714	Peng, Jingjing,Zhao, Lifen,Wang, Lanlan,et al. Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y(1) receptor antagonists[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,158:302-310.
APA	Peng, Jingjing.,Zhao, Lifen.,Wang, Lanlan.,Chen, Hui.,Qiu, Yunguang.,...&Liu, Hong.(2018).Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y(1) receptor antagonists.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,158,302-310.
MLA	Peng, Jingjing,et al."Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y(1) receptor antagonists".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 158(2018):302-310.