Discovery of dipiperidines as new antitubercular agents

被引：37

作者：

Bogatcheva, Elena ^{[1
]}

Hanrahan, Colleen ^{[1
]}

Chen, Ping ^{[1
]}

Gearhart, Jacqueline ^{[1
]}

Sacksteder, Katherine ^{[1
]}

Einck, Leo ^{[1
]}

Nacy, Carol ^{[1
]}

Protopopova, Marina ^{[1
]}

机构：

[1] Sequella Inc, Rockville, MD 20850 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 01期

关键词：

Tuberculosis; Antitubercular drugs; Dipiperidines; COMBINATORIAL LEAD OPTIMIZATION; TUBERCULOSIS; ETHAMBUTOL; SQ109; IDENTIFICATION; DRUGS;

D O I：

10.1016/j.bmcl.2009.10.135

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

As part of our ongoing research effort to develop new therapeutics for treatment of tuberculosis (TB), we synthesized a combinatorial library of 10,358 compounds on solid support using a pool-and-split technique and tested the resulting compounds for activity against Mycobacterium tuberculosis. Structure activity relationship (SAR) evaluation identified new compounds with antitubercular activity, including a novel hit series that is structurally unrelated to any existing antitubercular drugs, dipiperidines. Dipiperidine representatives exhibited MIC values as low as 7.8 mu M, the ability to induce promoter Rv0341 activated in response to cell wall biosynthesis inhibition, relatively low nonspecific cellular toxicity in the range of 30-162 mu M, and log P values less than 4. (C) 2009 Elsevier Ltd. All rights reserved.

引用

收藏

页码：201 / 205

页数：5

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