Design, synthesis, and SAR studies of novel and highly active tri-cyclic HIV integrase inhibitors

被引：41

作者：

Jin, Haolun

Cai, Ruby Z.

Schacherer, Laura

Jabri, Salman

Tsiang, Manuel

Fardis, Maria

Chen, Xiaowu

Chen, James M.

Kim, Choung U.

机构：

[1] Gilead Sci Inc, Foster City, CA 94404 USA

[2] Yale Univ, Dept Chem, New Haven, CT 06520 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 15期

关键词：

HIV; integrase; inhibitors; tri-cyclic; pyrolloquinoline; modeling;

D O I：

10.1016/j.bmcl.2006.05.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of tri-cyclic HIV integrase inhibitors were designed based on conformational analysis of 1,6-naphthyridine carboxamide compound L-870810 and docking the designed inhibitor into the active site of our integrase enzyme model. The efficient syntheses of pyrroloquinoline tri-cyclic analogs are described. The SAR studies resulted in the identification of a lead compound that is more potent and more soluble than L-870810. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：3989 / 3992

页数：4

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