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

被引：21

作者：

Spallarossa, Andrea ^{[1
]}

Cesarini, Sara ^{[1
]}

Ranise, Angelo ^{[1
]}

Schenone, Silvia ^{[1
]}

Bruno, Olga ^{[1
]}

Borassi, Alberto ^{[2
]}

La Colla, Paolo ^{[3
]}

Pezzullo, Margherita ^{[3
]}

Sanna, Giuseppina ^{[3
]}

Collu, Gabriella ^{[3
]}

Secci, Barbara ^{[3
]}

Loddo, Roberta ^{[3
]}

机构：

[1] Univ Genoa, Dipartimento Sci Farmaceut, I-16132 Genoa, Italy

[2] Univ Genoa, Dipartimento Chim & Chim Ind, I-16146 Genoa, Italy

[3] Univ Cagliari, Dipartimento Sci & Tecnol Biomed, I-09042 Cagliari, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 05期

关键词：

Acylthiocarbamates; HIV-1; Non-nucleoside reverse transcriptase inhibitors; Parallel synthesis; PETT COMPOUNDS; THIOUREA COMPOUNDS; BINDING; NNRTIS; STEREOCHEMISTRY; RESISTANCE; MOLSCRIPT; DESIGN; SERIES;

D O I：

10.1016/j.ejmech.2008.10.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：2190 / 2201

页数：12

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