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

doi:10.3390/molecules21091198

	Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives
	Liu, Guan-Nan 1,2; Luo, Rong-Hua 3,4; Zhou, Yu1 ; Zhang, Xing-Jie 3,4; Li, Jian 1; Yang, Liu-Meng 3,4; Zheng, Yong-Tang 3,4; Liu, Hong1
刊名	MOLECULES
	2016-09
卷号	21 期号:9
关键词	anti-HIV-1 integrase synthesis SAR AIDS
ISSN号	1420-3049
DOI	10.3390/molecules21091198
文献子类	Article
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 M) 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.
资助项目	Zhejiang Provincial Natural Science Foundation[LQ14B020004] ; National Natural Science Foundation of China[81220108025] ; National Natural Science Foundation of China[81302633] ; National Natural Science Foundation of China[2147220] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81102483] ; SA-SIBS Scholarship Program[00000000] ; National Health and Family Planning Commission[2012ZX09304-011] ; National Health and Family Planning Commission[2013ZX09401003-005] ; National Health and Family Planning Commission[2013ZX09507001] ; National Health and Family Planning Commission[2013ZX09507-002] ; National Health and Family Planning Commission[2014ZX09507002-001] ; Shanghai Science and Technology Development Fund[15DZ2291600] ; Thousand Talents Program in China[00000000] ; National Science and Technology Major Project[2009ZX09501-029] ; Yunnan Province[2007BC006] ; Knowledge Innovation Program of the Chinese Academy of Sciences[KFJ-EW-STS-026]
WOS关键词	RESISTANT INTEGRASE MUTANTS ; INHIBITORS ; RALTEGRAVIR ; HIV-1 ; DOLUTEGRAVIR ; ELVITEGRAVIR ; GENERATION ; INFECTION ; COMPLEXES ; POTENCY
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI AG
WOS记录号	WOS:000385479800095
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275907]
专题	药物化学研究室
通讯作者	Zheng, Yong-Tang; Liu, Hong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.China Jiliang Univ, Coll Life Sci, Hangzhou 310018, Zhejiang, Peoples R China; 3.Chinese Acad Sci, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China 4.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China;
推荐引用方式 GB/T 7714	Liu, Guan-Nan,Luo, Rong-Hua,Zhou, Yu,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).
APA	Liu, Guan-Nan.,Luo, Rong-Hua.,Zhou, Yu.,Zhang, Xing-Jie.,Li, Jian.,...&Liu, Hong.(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).
MLA	Liu, Guan-Nan,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).