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

• Published in: Journal of medicinal chemistry Vol. 47; no. 15; pp. 3892 - 3896
• Main Authors: Silvestri, Romano, Artico, Marino, De Martino, Gabriella, La Regina, Giuseppe, Loddo, Roberta, La Colla, Massimiliano, La Colla, Paolo
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15-07-2004
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Cell Line; Drug Resistance, Viral; HIV-1 - drug effects; HIV-1 - genetics; Humans; Indoles - chemical synthesis; Indoles - pharmacology; Indoles - toxicity; Medical sciences; Mutation; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - toxicity; Sulfones - chemical synthesis; Sulfones - pharmacology; Sulfones - toxicity; Organic hydrazide; Peptides; Sulfone; HIV-1 virus; Aminoamide; Nitrogen heterocycle; Tripeptide; Retroviridae; Lentivirus; Efavirenz; In vitro; Virus; Resistance; Structure activity relation; Chlorine Organic compounds; Bicyclic compound; Dipeptides; Antiviral; Aromatic compound; Human immunodeficiency virus; Mutation; Chemical synthesis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm031147e

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.