Rationally designed dual inhibitors of HIV reverse transcriptase and integrase

Zhengqiang Wang; Eric M. Bennett; Daniel J. Wilson; Christine Salomon; Robert Vince

doi:10.1021/jm070512p

Rationally designed dual inhibitors of HIV reverse transcriptase and integrase

Zhengqiang Wang, Eric M. Bennett, Daniel J. Wilson, Christine Salomon, Robert Vince

Center for Drug Design

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90 Scopus citations

Abstract

Bifunctional inhibitors were designed and synthesized based on 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)^a1 non-nucleoside reverse transcriptase (RT) inhibitors and diketoacid (DKA) integrase (IN) inhibitors. Biochemical studies revealed activity against RT and IN at low nanomolar and low micromolar concentrations, respectively. Exceptionally low IC₅₀ values from a cell-based assay were achieved along with remarkably high therapeutic indices. Compound 7 was identified as the best compound of the series (IC₅₀: 24 nM against RT, 4.4 μM against IN, and 10 nM against HIV-1).

Original language	English (US)
Pages (from-to)	3416-3419
Number of pages	4
Journal	Journal of medicinal chemistry
Volume	50
Issue number	15
DOIs	https://doi.org/10.1021/jm070512p
State	Published - Jul 26 2007

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AU - Salomon, Christine

AU - Vince, Robert

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Rationally designed dual inhibitors of HIV reverse transcriptase and integrase

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