Bioorganic & Medicinal Chemistry Letters 2012-06-15

Development of a series of 3-hydroxyquinolin-2(1H)-ones as selective inhibitors of HIV-1 reverse transcriptase associated RNase H activity

Virginie Suchaud, Fabrice Bailly, Cédric Lion, Enzo Tramontano, Francesca Esposito, Angela Corona, Frauke Christ, Zeger Debyser, Philippe Cotelle

Index: Bioorg. Med. Chem. Lett. 22(12) , 3988-92, (2012)

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Abstract

We report herein the synthesis of a series of 3-hydroxyquinolin-2(1H)-one derivatives. Esters and amide groups were introduced at position 4 of the basis scaffold and some modulations of the benzenic moiety were performed. Most compounds presented selective inhibitory properties in the 10-20 μM range against HIV-1 reverse transcriptase associated ribonuclease H activity, without affecting the integrase and reverse transcriptase DNA polymerase activities. Unfortunately all tested compounds exhibited high cellular cytotoxicity in cell culture which limited their applications as antiviral agents.Copyright © 2012 Elsevier Ltd. All rights reserved.