Discovery of dipiperidines as new antitubercular agents |
| |
Authors: | Elena Bogatcheva Colleen Hanrahan Ping Chen Jacqueline Gearhart Katherine Sacksteder Leo Einck Carol Nacy Marina Protopopova |
| |
Affiliation: | Sequella, Inc., 9610 Medical center Drive, Suite 200, Rockville, MD 20850, USA |
| |
Abstract: | 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 μM, 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 μM, and log P values less than 4. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|