Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 分子免疫药理学

	Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives
	Liu GN 1,2; Luo RH 3; Yang LM 3; Zheng YT[]3; Liu H[]2; Zhou Y 2; Zhang XJ 3; Li J 2
刊名	Molecules
	2016
卷号	21 期号:9 页码:e1198
关键词	AIDS SAR anti-HIV-1 integrase synthesis
通讯作者	zhengyt@mail.kiz.ac.cn ; hliu@mail.shcnc.ac.cn
合作状况	其它
英文摘要	The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN) inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenyl)ethyl]-pyrrole-2,5-dione scaffolds to design 35 novel compounds with improved biological activities against HIV-1. These new compounds show single-digit micromolar antiviral potencies against HIV-1 and low toxicity. Among of them, compound 9g and 15i had potent anti-HIV-1 activities (EC50 < 5 μM) and excellent therapeutic index (TI, CC50/EC50 > 100). These two compounds have potential as lead compounds for further optimization into clinical anti-HIV-1 agents.
收录类别	SCI
资助信息	We gratefully acknowledge financial support from the Zhejiang Provincial Natural Science Foundation (LQ14B020004), the National Natural Science Foundation of China (81220108025, 81302633, 2147220 and 91229204), SA-SIBS scholarship program, the National Health and Family Planning Commission (2012ZX09304-011, 2013ZX09401003-005, 2013ZX09507001, 2013ZX09507-002 and 2014ZX09507002-001), Shanghai Science and Technology Development Fund (15DZ2291600), the Thousand Talents Program in China, the National Natural Science Foundation of China (81102483), the National Science and Technology Major Project (2009ZX09501-029), Yunnan Province (2007BC006) and the Knowledge Innovation Program of the Chinese Academy of Sciences (KFJ-EW-STS-026).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/10468]
专题	昆明动物研究所_分子免疫药理学昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.College of Life Sciences, China Jiliang University, Hangzhou 310018, Zhejiang, China 2.CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China 3.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
推荐引用方式 GB/T 7714	Liu GN,Luo RH,Yang LM,et al. Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives[J]. Molecules,2016,21(9):e1198.
APA	Liu GN.,Luo RH.,Yang LM.,Zheng YT[].,Liu H[].,...&Li J.(2016).Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives.Molecules,21(9),e1198.
MLA	Liu GN,et al."Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives".Molecules 21.9(2016):e1198.