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

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

  • Eur J Med Chem. 2009 May;44(5):2190-201. doi: 10.1016/j.ejmech.2008.10.032.
Andrea Spallarossa 1,  Sara Cesarini,  Angelo Ranise,  Silvia Schenone,  Olga Bruno,  Alberto Borassi,  Paolo La Colla,  Margherita Pezzullo,  Giuseppina Sanna,  Gabriella Collu,  Barbara Secci,  Roberta Loddo
Affiliations

Affiliation

  • 1 Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy.
PMID: 19058881 DOI: 10.1016/j.ejmech.2008.10.032
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.

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