Synthesis and antiviral activity of new dimeric inhibitors against HIV-1

被引：21

作者：

Danel, Krzysztof ^{[1
]}

Larsen, Louise M. ^{[1
]}

Pedersen, Erik B. ^{[1
]}

Sanna, Giuseppina

La Colla, Paolo

Loddo, Roberta

机构：

[1] Univ So Denmark, Nucl Acid Ctr, Dept Phys & Chem, DK-5230 Odense, Denmark

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 01期

关键词：

HIV-1; NNRTI; synthesis; AZT; TNK-651; MKC-442; Sonogashira reaction; click chemistry; NRTI; nucleobase; reverse transcriptase; acetylene; D-norgestrel; mutant; virus; drug-resistant; efavirenz; anti-viral activity; uracil;

D O I：

10.1016/j.bmc.2007.09.015

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：

This paper describes the synthesis and the antiviral activities of dimeric compounds derived from homo and asymmetric combinations of N-1 propynyloxymethyl analogues 1a,b of MKC-442, an N-1 4-iodobenzyloxymethyl analogue of TNK-651 5, potent contraceptive norgestrel and AZT. They were obtained by Sonogashira reaction, 'click' chemistry or Pd-catalyzed oxidative coupling. The iodo precursor 5 turned out as a potent compound against wild type and mutated HIV-1 virus. All dimeric compounds showed lower activity against HIV-1 than MKC-442, except the asymmetric dimer of AZT and 1a which showed an activity comparable to MKC-442. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：511 / 517

页数：7

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