1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyluracils as potent anti-HIV-1 agents

Mikhail S. Novikov, Olga N. Ivanova, Alexander V. Ivanov, Alexander A. Ozerov, Vladimir T. Valuev-Elliston, Kartik Temburnikar, Galina V. Gurskaya, Sergey N. Kochetkov, Christophe Pannecouque, Jan Balzarini, Katherine L. Seley-Radtke

Research output: Contribution to journalArticlepeer-review

Abstract

Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1. Herein we present the synthesis for a series of N1-alkylated uracil derivatives bearing ω-(2-benzyl- and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. Further evaluation revealed that the inhibitors were active against most nevirapine-resistant mono- and di-substituted RTs with the exception of the V106A RT. Thus, the candidate compounds can be regarded as potential lead compounds against the wild-type virus and drug-resistant forms.

Original languageEnglish (US)
Pages (from-to)5794-5802
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number19
DOIs
StatePublished - Oct 1 2011

Keywords

  • Benzophenone
  • HIV-1
  • Non-nucleoside reverse transcriptase inhibitors
  • Reverse transcriptase
  • Uracil

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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