Computational strategies in discovering novel non-nucleoside inhibitors of HIV-1 RT

被引：64

作者：

Barreca, ML

Rao, A

De Luca, L

Zappalà, L

Monforte, AM

Maga, G

Pannecouque, C

Balzarini, J

De Clercq, E

Chimirri, A

Monforte, P

机构：

[1] Univ Messina, Dipartimento Farm Chim, I-98168 Messina, Italy

[2] CNR, Ist Genet Mol, IGM, I-27100 Pavia, Italy

[3] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 09期

关键词：

D O I：

10.1021/jm049279a

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a scaffold. Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs.

引用

页码：3433 / 3437

页数：5

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