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2
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本文引用的文献

1
Structure-Activity Relationship Studies of HIV-1 Integrase Oligonucleotide Inhibitors.HIV-1整合酶寡核苷酸抑制剂的构效关系研究
ACS Med Chem Lett. 2011 Apr 19;2(7):532-7. doi: 10.1021/ml200066k. eCollection 2011 Jul 14.
2
2-Hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs), novel inhibitors of HIV integrase with a high barrier to resistance.2-羟基异喹啉-1,3(2H,4H)-二酮（HIDs），新型 HIV 整合酶抑制剂，具有高耐药屏障。
ACS Chem Biol. 2013;8(6):1187-94. doi: 10.1021/cb4000426. Epub 2013 Apr 2.
3
3'-processing and strand transfer catalysed by retroviral integrase in crystallo.在晶体中通过逆转录病毒整合酶进行 3'-加工和链转移。
EMBO J. 2012 Jun 29;31(13):3020-8. doi: 10.1038/emboj.2012.118. Epub 2012 May 11.
4
The elvitegravir Quad pill: the first once-daily dual-target anti-HIV tablet.艾维雷韦 Quad 片：首款每日一次的双靶抗 HIV 片剂。
Expert Opin Investig Drugs. 2012 Jul;21(7):901-4. doi: 10.1517/13543784.2012.685653. Epub 2012 May 10.
5
Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir.使用从拉替拉韦治疗失败的患者中筛选出的克隆病毒变异株评估新型整合酶抑制剂多替拉韦（S/GSK1349572）的交叉耐药谱。
J Infect Dis. 2011 Dec 1;204(11):1811-5. doi: 10.1093/infdis/jir636. Epub 2011 Oct 7.
6
MK-0536 inhibits HIV-1 integrases resistant to raltegravir.MK-0536 抑制对拉替拉韦耐药的 HIV-1 整合酶。
Antimicrob Agents Chemother. 2011 Nov;55(11):5127-33. doi: 10.1128/AAC.05288-11. Epub 2011 Aug 29.
7
Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572).第二代整合酶链转移抑制剂多替拉韦（S/GSK1349572）的结构和功能分析。
Mol Pharmacol. 2011 Oct;80(4):565-72. doi: 10.1124/mol.111.073189. Epub 2011 Jun 30.
8
N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase.嘧啶-2,4-二酮的N-3羟基化产生HIV逆转录酶和整合酶的双重抑制剂。
ACS Med Chem Lett. 2011 Jan;2(1):63-67. doi: 10.1021/ml1002162.
9
S/GSK1349572, a new integrase inhibitor for the treatment of HIV: promises and challenges.S/GSK1349572，一种新型整合酶抑制剂，用于治疗 HIV：前景与挑战。
Expert Opin Investig Drugs. 2011 Apr;20(4):537-48. doi: 10.1517/13543784.2011.562189. Epub 2011 Mar 8.
10
Magnesium chelating 2-hydroxyisoquinoline-1,3(2H,4H)-diones, as inhibitors of HIV-1 integrase and/or the HIV-1 reverse transcriptase ribonuclease H domain: discovery of a novel selective inhibitor of the ribonuclease H function.螯合 2-羟基异喹啉-1,3(2H,4H)-二酮的镁，作为 HIV-1 整合酶和/或 HIV-1 逆转录酶核糖核酸酶 H 结构域的抑制剂：新型核糖核酸酶 H 功能选择性抑制剂的发现。
J Med Chem. 2011 Mar 24;54(6):1812-24. doi: 10.1021/jm1014692. Epub 2011 Mar 2.

4-取代的2-羟基异喹啉-1,3(2H,4H)-二酮作为一类新型HIV-1整合酶抑制剂

4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors.

作者信息

Billamboz Muriel, Suchaud Virginie, Bailly Fabrice, Lion Cedric, Demeulemeester Jonas, Calmels Christina, Andréola Marie-Line, Christ Frauke, Debyser Zeger, Cotelle Philippe

机构信息

Université Lille Nord de France , F-59000 Lille, France ; Université Lille 1 Sciences & Technologies , EA 4478 Chimie Moléculaire et Formulation, F-59655 Villeneuve d'Ascq, France.

KU Leuven , Molecular Virology and Gene Therapy (VCTB+5), Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.

出版信息

ACS Med Chem Lett. 2013 May 17;4(7):606-11. doi: 10.1021/ml400009t. eCollection 2013 Jul 11.

DOI:10.1021/ml400009t
PMID:24900718
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4027527/
Abstract

A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at position 4 by carboxamido chains was beneficial for antiviral activity since reproducible low micromolar anti-HIV activities were obtained for the first time within this scaffold.

摘要

对一系列具有N-羟基酰亚胺螯合功能的2-羟基-1,3-二氧代异喹啉-4-甲酰胺进行了抗人免疫缺陷病毒1型整合酶（HIV-1 IN）抑制特性的评估。几种衍生物显示出低纳摩尔的IC50值，与临床使用的拉替拉韦相当。一种化合物对主要的IN催化反应，即链转移（ST）和3'加工（3'-P）均有显著作用，强调了一种新的IN抑制机制，使其成为一种潜在的新一代IN抑制剂。在4位用羧酰胺链取代2-羟基异喹啉-1,3-二酮骨架有利于抗病毒活性，因为首次在该骨架内获得了可重复的低微摩尔抗HIV活性。