title: Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance mutations: synthesis and SAR studies.
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.
authors.affiliation: Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università di Roma La Sapienza, Piazzale A. Moro 5, Italy. romano.silvestri@uniroma1.it
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
authors.forename: Gabriella
authors.initials: G
authors.lastname: De Martino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.forename: Marino
authors.initials: M
authors.lastname: Artico
authors.forename: Silvio
authors.initials: S
authors.lastname: Massa
authors.forename: Laura
authors.initials: L
authors.lastname: Vargiu
authors.forename: Massimo
authors.initials: M
authors.lastname: Mura
authors.forename: Anna Giulia
authors.initials: AG
authors.lastname: Loi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Marceddu
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D024882:Drug Resistance, Viral / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; D013450:Sulfones