Discovery and Crystallography of Bicyclic Arylaminoazines As Potent Inhibitors of HIV-1 Reverse Transcriptase

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2015 Jul 14

PMID 26166629

Citations 8

Authors

Won-Gil Lee

Kathleen M Frey

Ricardo Gallardo-Macias

Krasimir A Spasov

Albert H Chan

Karen S Anderson

William L Jorgensen

Affiliations

Soon will be listed here.

Abstract

Non-nucleoside inhibitors of HIV-1 reverse transcriptase (HIV-RT) are reported that incorporate a 7-indolizinylamino or 2-naphthylamino substituent on a pyrimidine or 1,3,5-triazine core. The most potent compounds show below 10 nanomolar activity towards wild-type HIV-1 and variants bearing Tyr181Cys and Lys103Asn/Tyr181Cys resistance mutations. The compounds also feature good aqueous solubility. Crystal structures for two complexes enhance the analysis of the structure-activity data.

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