1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents

  • Bioorg Med Chem. 2011 Oct 1;19(19):5794-802. doi: 10.1016/j.bmc.2011.08.025.
Mikhail S Novikov  1 ,  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
Affiliations
  • 1. Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Paversushikh Bortsov Sq., 1, Volgograd 400131, Russia.
PMID: 21903401 DOI: 10.1016/j.bmc.2011.08.025
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.