期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 27, 期 23, 页码 5190-5196出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2017.10.042
关键词
Bedaquiline; Bedaquiline analogues; Tuberculosis; Drug development
资金
- Bill and Melinda Gates Foundation, Seattle, United States [OPP1017459]
- U.S. Agency for International Development ( USAID), Ronald Reagan Building Washington, DC, United States [GHS-A-00-08-00012-00]
- U.K. Department for International Development (DFID), Whitehall, London, England
- Irish Aid, Henry Street, Limerick, Eire
- Bill and Melinda Gates Foundation [OPP1017459] Funding Source: Bill and Melinda Gates Foundation
Analogues of bedaquiline where the phenyl B-unit was replaced with monocyclic heterocycles of widely differing lipophilicity (thiophenes, furans, pyridines) were synthesised and evaluated. While there was an expected broad positive correlation between lipophilicity and anti-TB activity, the 4-pyridyl derivatives appeared to have an additional contribution to antibacterial potency. The majority of the compounds were (desirably) more polar and had higher rates of clearance than bedaquiline, and showed acceptable oral bioavailability, but there was only limited (and unpredictable) improvement in their hERG liability. (C) 2017 The Authors. Published by Elsevier Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据