Parallel synthesis, molecular modelling and further structure–activity relationship studies of new acylthiocarbamates as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

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• 作者：Andrea Spallarossa ; Sara Cesarini ; Angelo Ranise ; Silvia Schenone ; Olga Bruno ; Alberto Borassi ; Paolo La Colla ; Margherita Pezzullo ; Giuseppina Sanna ; Gabriella Collu ; Barbara Secci ; Roberta Loddo
• 关键词：Acylthiocarbamates ; HIV-1 ; Non-nucleoside reverse transcriptase inhibitors ; Parallel synthesis
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：May 2009
• 年：2009
• 卷：44
• 期：5
• 页码：2190-2201
• 全文大小：468 K

文摘

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 (EC₅₀ = 1.5 nM). 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.