Simple, short peptide derivatives of a sulfonylindolecarboxamide (L-737,126) active in vitro against HIV-1 wild type and variants carrying non-nucleoside reverse transcriptase inhibitor resistance mutations

  • J Med Chem. 2004 Jul 15;47(15):3892-6. doi: 10.1021/jm031147e.
Romano Silvestri  1 ,  Marino Artico ,  Gabriella De Martino ,  Giuseppe La Regina ,  Roberta Loddo ,  Massimiliano La Colla ,  Massimo Mura ,  Paolo La Colla
Affiliations
  • 1. Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università di Roma La Sapienza, Piazzale A. Moro 5, I-00185 Rome, Italy. [email protected]
PMID: 15239667 DOI: 10.1021/jm031147e
Abstract

Non-nucleoside Reverse Transcriptase inhibitors (NNRTIs) active against NNRTI-resistant mutants were obtained by introducing two methyl groups at positions 3 and 5 of the benzenesulfonyl moiety of L-737,126 (1) and coupling one to three glycinamide/alaninamide units to its carboxyamide function. In cell-based assays, the new derivatives showed activities against HIV-1 wild type and NNRTI-resistant mutants [Y181C, K103N-Y181C, and triple mutant (K103R, V179D, P225H) highly resistant to efavirenz] superior to that of the parent indole derivative 1.