Novel Indolyl Aryl Sulfones Active against HIV-1 Carrying NNRTI Resistance Mutations:  Synthesis and SAR Studies

The potent anti-HIV-1 activities of L-737,126 (2) and PAS sulfones prompted us to design and test against HIV-1 in acutely infected MT-4 cells a number of novel 1- and 3-benzenesulfonylindoles. Indoles belonging to the 1-benzenesulfonyl series were found poorly or totally inactive. On the contrary,...

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Veröffentlicht in:Journal of medicinal chemistry 2003-06, Vol.46 (12), p.2482-2493
Hauptverfasser: Silvestri, Romano, De Martino, Gabriella, La Regina, Giuseppe, Artico, Marino, Massa, Silvio, Vargiu, Laura, Mura, Massimo, Loi, Anna Giulia, Marceddu, Tiziana, La Colla, Paolo
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Sprache:eng
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Zusammenfassung:The potent anti-HIV-1 activities of L-737,126 (2) and PAS sulfones prompted us to design and test against HIV-1 in acutely infected MT-4 cells a number of novel 1- and 3-benzenesulfonylindoles. Indoles belonging to the 1-benzenesulfonyl series were found poorly or totally inactive. On the contrary, some of the 3-benzenesulfonyl derivatives turned out to be as potent as 2, being endowed with potencies in the low nanomolar concentration range. In particular, (2-methylphenyl)sulfonyl (72) and (3-methylphenyl)sulfonyl (73) derivatives showed EC50 values of 1 nM. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of 2 furnished derivatives (80 and 83) which showed very potent and selective anti-HIV-1 activity not only against the wt strain, but also against mutants carrying NNRTI-resistant mutations at positions 103 and 181 of the reverse transcriptase gene.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm0211063