Picomolar Inhibitors of HIV-1 Reverse Transcriptase: Design and Crystallography of Naphthyl Phenyl Ethers

被引：36

作者：

Lee, Won-Gil ^{[1
]}

Frey, Kathleen M. ^{[2
]}

Gallardo-Macias, Ricardo ^{[1
]}

Spasov, Krasimir A. ^{[2
]}

Bollini, Mariela ^{[1
]}

Anderson, Karen S. ^{[2
]}

Jorgensen, William L. ^{[1
]}

机构：

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

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

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2014年 / 5卷 / 11期

基金：

美国国家卫生研究院;

关键词：

Anti-HIV agents; NNRTIs; protein crystallography; DRUG; OPTIMIZATION; SOLUBILITY; DISCOVERY; SEARCH; NNRTIS; AGENTS;

D O I：

10.1021/ml5003713

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Catechol diethers that incorporate a 6-cyano-1-naphthyl substituent have been explored as non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Promising compounds are reported that show midpicomolar activity against the wild-type virus and sub-20 nM activity against viral variants bearing Tyr181Cys and Lys103Asn mutations in HIV-RT. An X-ray crystal structure at 2.49 angstrom resolution is also reported for the key compound 6e with HIV-RT.

引用

收藏

页码：1259 / 1262

页数：4

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