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 EC(50) 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.

Novel Indolyl Aryl Sulfones Active against HIV-1 Carrying NNRTI Resistance Mutations: Synthesis and SAR Studies / Silvestri, Romano; DE MARTINO, G.; LA REGINA, Giuseppe; Artico, Marino; Massa, S.; Vargiu, L.; Mura, M.; Loi, A. G.; Marceddu, T.; LA COLLA, P.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 46(2003), pp. 2482-2493. [10.1021/jm0211063]

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

SILVESTRI, Romano;LA REGINA, GIUSEPPE;ARTICO, Marino;
2003

Abstract

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 EC(50) 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/249931
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