Novel indole sulfides as potent HIV-1 NNRTIs

被引：22

作者：

Brigg, Siobhan ^{[1
]}

Pribut, Nicole ^{[1
]}

Basson, Adriaan E. ^{[2
]}

Avgenikos, Moscos ^{[1
]}

Venter, Reinhardt ^{[1
]}

Blackie, Margaret A. ^{[1
]}

van Otterlo, Willem A. L. ^{[1
]}

Pelly, Stephen C. ^{[1
]}

机构：

[1] Univ Stellenbosch, Dept Chem & Polymer Sci, Private Bag X1, ZA-7602 Matieland, Western Cape, South Africa

[2] Natl Inst Communicable Dis, Ctr HIV & STI, HIV Virol Sect, Private Bag X4, ZA-2131 Johannesburg, South Africa

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 06期

基金：

英国医学研究理事会; 新加坡国家研究基金会;

关键词：

HIV; NNRTI; Indole; Sulfides; TRANSCRIPTASE INHIBITORS NNRTIS; REVERSE-TRANSCRIPTASE; ARYL SULFONES; RESISTANCE MUTATIONS; WILD-TYPE; IN-VITRO; DERIVATIVES; DESIGN; SUSCEPTIBILITY; DISCOVERY;

D O I：

10.1016/j.bmcl.2016.02.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted S(N)1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1580 / 1584

页数：5

共 24 条

[1]

[Anonymous], J MED CHEM, DOI 10.10-763321/acs.jmedchem.5b00229

[2] Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV [J].