Structure-activity relationship of new anti-tuberculosis agents derived from oxazoline and oxazole benzyl esters.

ABSTRACT: During the syntheses and studies of natural iron chelators (mycobactins), we serendipitously discovered that a simple, small molecule, oxazoline-containing intermediate 3 displayed surprising anti-tuberculosis activity (MIC of 7.7 microM, average). Herein we report elaboration of SAR around this hit as well as the syntheses and evaluation of a hundred oxazoline- and oxazole-containing compounds derived from an efficient three step process: 1) formation of beta-hydroxy amides with serine or threonine; 2) cyclization to afford oxazolines; and 3) dehydration to give the corresponding oxazoles. A number of compounds prepared by this method were shown to possess impressive activity against Mycobacterium tuberculosis, extremely low toxicity and therefore high therapeutic indexes, as well as acti

SUBMITTER: Moraski GC 

PROVIDER: S-EPMC2843756 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature