Generation and exploration of new classes of antitubercular agents: The optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2-a]pyridines and isomeric 5,6-fused scaffolds.

Garrett C Moraski, Lowell D Markley, Mayland Chang, Sanghyun Cho, Scott G Franzblau, Chang Hwa Hwang, Helena Boshoff, Marvin J Miller

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46656, USA.

Bioorganic & medicinal chemistry 2012 Apr 1

filter terms:

Tuberculosis (TB) is a devastating disease resulting in a death every 20s. Thus, new drugs are urgently needed. Herein we report ten classes of compounds-oxazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole, imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine and imidazo[1,2-c]pyrimidine-which have good (micromolar) to excellent (sub-micromolar) antitubercular potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC's as low as <0.195 μM (9 and 11). Overall, the imidazo[1,2-a]pyridine class was determined to be most promising, with potency similar to isoniazid and PA-824 against replicating Mtb H(37)Rv, clinically relevant drug sensitive, multi- and extensively resistant Mtb strains as well as having good in vitro metabolic stability. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Garrett C Moraski, Lowell D Markley, Mayland Chang, Sanghyun Cho, Scott G Franzblau, Chang Hwa Hwang, Helena Boshoff, Marvin J Miller. Generation and exploration of new classes of antitubercular agents: The optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2-a]pyridines and isomeric 5,6-fused scaffolds. Bioorganic & medicinal chemistry. 2012 Apr 1;20(7):2214-20