A refined pharmacophore model for HIV-1 integrase inhibitors: Optimization of potency in the 1H-benzylindole series

被引:33
作者
De Luca, Laura [1 ]
Barreca, Maria Letizia [2 ]
Ferro, Stefania [1 ]
Iraci, Nunzio [1 ]
Michiels, Martine [3 ,4 ]
Christ, Frauke [3 ,4 ]
Debyser, Zeger [3 ,4 ]
Witvrouw, Myriam [3 ,4 ]
Chimirri, Alba [1 ]
机构
[1] Univ Messina, Dipartimento Farmaco Chim, I-98168 Messina, Italy
[2] Dipartiment Chim & Technol Farmaco, I-06123 Perugia, Italy
[3] Katholieke Univ Leuven, B-3000 Louvain, Belgium
[4] IRC KULAK, B-3000 Louvain, Belgium
关键词
integrase; HIV; DKAs; pharmacophore model; synthesis of indole derivatives;
D O I
10.1016/j.bmcl.2008.03.089
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
We report herein the development of a new three-dimensional pharmacophore model for HIV-1 integrase inhibitors which led to the discovery of some 4-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acids that are able to specifically inhibit the strand transfer step of integration at nanomolar concentration. The synthesis of the new designed molecules is also described. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2891 / 2895
页数:5
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