The design of 8-hydroxyquinoline tetracyclic lactams as HIV-1 integrase strand transfer inhibitors

被引：24
作者：
Velthuisen, Emile J. [1 ]
Johns, Brian A. [1 ]
Temelkoff, David P. [1 ]
Brown, Kevin W. [1 ]
Danehower, Susan C. [1 ]
机构：
[1] GlaxoSmithKline Res & Dev Ltd, Infect Dis Therapeut Area Unit, 5 Moore Dr, Res Triangle Pk, NC 27709 USA
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 117卷
关键词：
HIV; AIDS; Integrase; Integrase inhibitor; Strand transfer inhibitor; Quinoline; TREATMENT-EXPERIENCED PATIENTS; DERIVATIVES; RALTEGRAVIR; RESISTANT; POTENT; ELVITEGRAVIR; ALKALOIDS; MECHANISM; EFFICACY; INTASOME;
D O I：
10.1016/j.ejmech.2016.03.038
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A novel series of HIV-1 integrase strand transfer inhibitors were designed using the venerable two-metal binding pharmacophore model and incorporating structural elements from two different literature scaffolds. This manuscript describes a number of 8-hydroxyquinoline tetracyclic lactams with exceptional antiviral activity against HIV-1 and little loss of potency against the IN signature resistance mutations Q148K and G140S/Q148H. (C) 2016 Elsevier Masson SAS. All rights reserved.
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收藏
页码：99 / 112
页数：14
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