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

Giuseppe La Regina (1) , Antonio Coluccia (1) , Andrea Brancale (2) , Francesco Piscitelli (1) , Valeria Famiglini (1) , Sandro Cosconati (3) , Giovanni Maga (4) , Alberta Samuele , Emmanuel Gonzalez , Bonaventura Clotet (1, 5) , Dominique Schols (6) , José A Esté , Ettore Novellino (7) , Romano Silvestri (1)

1 Department of Medicinal Chemistry and Technologies
2 Welsh School of Pharmacy
3 Department of Pharmaceutical Chemistry and Toxicology
4 DNA Enzymology and Molecular Virology Section
5 IrsiCaixa (Institut de Recerca de la Sida)
6 Rega Institute for Medical Research [Leuven, België]
7 Department of Pharmacy Naples

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.

Domaines: Sciences pharmaceutiques

Giuseppe La Regina, Antonio Coluccia, Andrea Brancale, Francesco Piscitelli, Valeria Famiglini, et al.. New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors.. Journal of Medicinal Chemistry, 2012, 55 (14), pp.6634-8. ⟨10.1021/jm300477h⟩. ⟨pasteur-00969585⟩