title: Parallel synthesis, molecular modelling and further structure-activity relationship studies of new acylthiocarbamates as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
abstract: The structure-activity relationships (SARs) of acylthiocarbamates (ATCs), a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors, have been expanded. Sixty-six new analogues were prepared by parallel solution-phase synthesis. In general, the potency of new ATCs was better than that of the first series and O-[2-phthalimidoethyl] 4-chlorophenyl(3-nitrobenzoyl) thiocarbamate turned out to be the most potent ATC so far synthesized (EC(50)=1.5nM). Several ATCs were active at micromolar concentrations against HIV-1 strains carrying the RT Y181C mutation and one of them was also moderately active against the K103R variant. Docking simulations were carried out to rationalize the most relevant SARs.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Spallarossa
authors.forename: Sara
authors.initials: S
authors.lastname: Cesarini
authors.forename: Angelo
authors.initials: A
authors.lastname: Ranise
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.forename: Olga
authors.initials: O
authors.lastname: Bruno
authors.forename: Alberto
authors.initials: A
authors.lastname: Borassi
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
authors.forename: Margherita
authors.initials: M
authors.lastname: Pezzullo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sanna
authors.forename: Gabriella
authors.initials: G
authors.lastname: Collu
authors.forename: Barbara
authors.initials: B
authors.lastname: Secci
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
mesh_terms: D003198:Computer Simulation; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D020125:Mutation, Missense; D011485:Protein Binding; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D018894:Reverse Transcriptase Inhibitors; D013859:Thiocarbamates; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase