title: Computer-assisted design, synthesis and biological evaluation of novel pyrrolyl heteroaryl sulfones targeted at HIV-1 reverse transcriptase as non-nucleoside inhibitors.
abstract: Three pyrrolyl heteroaryl sulfones (ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxyla te, ethyl 1-[(1H-benzimidazol-5(6)-yl)sulfonyl]-1H-pyrrole-2-carboxylate and ethyl 1-[(1H-benzotriazol-5(6)-yl)sulfonyl]-1H-pyrrole-2-carboxylate) were designed as novel HIV-1 reverse transcriptase non-nucleoside inhibitors using structure-based computational methods. Although these compounds were inactive in the cell-based assay, they inhibited the target enzyme with micromolar potency (IC50s = 2 microM, 3 microM and 9 microM, respectively).
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università degli Studi di Roma, La Sapienza, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Silvestri
authors.forename: M
authors.initials: M
authors.lastname: Artico
authors.forename: G
authors.initials: G
authors.lastname: De Martino
authors.forename: E
authors.initials: E
authors.lastname: Novellino
authors.forename: G
authors.initials: G
authors.lastname: Greco
authors.forename: A
authors.initials: A
authors.lastname: Lavecchia
authors.forename: S
authors.initials: S
authors.lastname: Massa
authors.forename: A G
authors.initials: AG
authors.lastname: Loi
authors.forename: S
authors.initials: S
authors.lastname: Doratiotto
authors.forename: P
authors.initials: P
authors.lastname: La Colla
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017076:Computer-Aided Design; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D020128:Inhibitory Concentration 50; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects*; D013450:Sulfones / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D013450:Sulfones; C002986:2-pyrrolecarboxylic acid; D011392:Proline; D012194:RNA-Directed DNA Polymerase