Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors

doi:10.1016/j.ejmech.2018.01.008

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	Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors
	Lu, Dong 1,2; Liu, Jianan 1,2; Zhang, Yunzhe 3; Liu, Feifei 1,2; Zeng, Limin 1; Peng, Runze 1,2; Yang, Li 1; Ying, Huazhou 3; Tang, Wei1 ; Chen, Wuhong 1
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2018-02-10
卷号	145 页码:328-337
关键词	Phthalazinone Dengue virus Inhibitor Optimization SAR
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2018.01.008
文献子类	Article
英文摘要	Using a dengue replicon cell line-based screening, we identified 3-(dimethylamino)propyl(3-((4-(4-fluorophenyl)-1-oxophthalazin-2(1H)-yl)methypphenyl)carbamate (10a) as a potent DENV-2 inhibitor, with an IC50 value of 0.64 mu M. A series of novel phthalazinone derivatives based on hit 10a were synthesized and evaluated for their in vitro anti-DENV activity and cytotoxicity. The subsequent SAR study and optimization led to the discovery of the most promising compound 141, which displayed potent anti-DENV-2 activity, with low IC50 value against DENV-2 RNA replication of 0.13 mu M and high selectivity (SI = 89.2) with acceptable pharmacokinetics profiles. (C) 2018 Elsevier Masson SAS. All rights reserved.
资助项目	National Key Research and Development Program of China[2016YFC1200400] ; Defense Technology Innovation Fund, Chinese Academy of Sciences[CXJJ-17-Q147] ; National Natural Science Foundation of China[00000000]
WOS关键词	INFECTION ; PERSPECTIVE ; PROSPECTS ; PROGRESS
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:000425198200026
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279906]
专题	药理学第一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药物发现与设计中心药物化学研究室
通讯作者	Tong, Xiankun; Liu, Tao; Hu, Youhong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Lu, Dong,Liu, Jianan,Zhang, Yunzhe,et al. Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,145:328-337.
APA	Lu, Dong.,Liu, Jianan.,Zhang, Yunzhe.,Liu, Feifei.,Zeng, Limin.,...&Hu, Youhong.(2018).Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,145,328-337.
MLA	Lu, Dong,et al."Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 145(2018):328-337.