Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

被引：47

作者：

Thakur, Vinay V.

Kim, Joseph T.

Hamilton, Andrew D.

Bailey, Christopher M.

Domaoal, Robert A.

Wang, Ligong

Anderson, Karen S. ^{[1
]}

Jorgensen, William L.

机构：

[1] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 21期

关键词：

NNRTI; anti-HIV; structure-based drug design; triazinylamine; 2-pyrimidinylamine; free energy perturbation;

D O I：

10.1016/j.bmcl.2006.08.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het = 2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5664 / 5667

页数：4

共 10 条

[1] Synthetic study of substituted arylsulfonylphenylbenzamides [J].