Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors.: Part 2:: Parallel synthesis, molecular modelling and structure-activity relationship studies on analogues of O-(2-phenylethyl)-N-phenylthiocarbamate

被引：12

作者：

Cesarini, Sara ^{[1
]}

Spallarossa, Andrea ^{[1
]}

Ranise, Angelo ^{[1
]}

Bruno, Olga ^{[1
]}

La Colla, Paolo ^{[2
]}

Secci, Barbara ^{[2
]}

Collu, Gabriella ^{[2
]}

Loddo, Roberta ^{[2
]}

机构：

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

[2] Univ Cagliari, Dipartimento Sci & Technol Biomed, I-09042 Cagliari, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 07期

关键词：

thiocarbamates; HIV-1; non-nucleoside reverse transcriptase inhibitors; parallel synthesis;

D O I：

10.1016/j.bmc.2007.12.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To acquire further insight into the structure-activity relationship (SAR) of the thiocarbamates (TCs) described in the preceding work, 57 analogues of the lead compound O-(2-phenylethyl)-N-phenylthiocarbamate I were prepared by parallel solution-phase synthesis. We varied the 2-phenylethyl moiety (mono-substitution on the phenyl ring and modi. cation of the ethyl linker), keeping constant the N-phenyl ring substitutions which have given the best results in the previous series. Most of the new TCs inhibited wild-type HIV-1 at micro-and nanomolar concentrations in MT-4 cell-based assays. Some TCs were also active at micromolar concentrations against the Y181C and/or K103N/Y181C resistant mutants. The SARs were rationalized by docking simulations. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：4173 / 4185

页数：13

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