New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors

  • J Med Chem. 2012 Jul 26;55(14):6634-8. doi: 10.1021/jm300477h.
Giuseppe La Regina  1 ,  Antonio Coluccia ,  Andrea Brancale ,  Francesco Piscitelli ,  Valeria Famiglini ,  Sandro Cosconati ,  Giovanni Maga ,  Alberta Samuele ,  Emmanuel Gonzalez ,  Bonaventura Clotet ,  Dominique Schols ,  José A Esté ,  Ettore Novellino ,  Romano Silvestri
Affiliations
  • 1. Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
PMID: 22712652 DOI: 10.1021/jm300477h
Abstract

New indolylarylsulfone (IAS) derivatives bearing nitrogen containing substituents at the indole-2-carboxamide inhibited the HIV-1 WT in MT-4 cells at low nanomolar concentrations. In particular, compound 9 was uniformly effective against the mutant Y181C, Y188L, and K103N HIV-1 strains; it was highly active against the multidrug resistant mutant IRLL98 HIV-1 strain bearing the K101Q, Y181C, and G190A mutations conferring resistance to NVP, DLV, and EFV and several HIV-1 clades A in PBMC.