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

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• 作者：Garrett C. Moraski^a ; Lowell D. Markley^a ; Mayland Chang^a ; Sanghyun Cho^b ; Scott G. Franzblau^b ; Chang Hwa Hwang^b ; Helena Boshoff^c ; Marvin J. Miller^a ; ^{mmiller1@nd.edu}
• 关键词：Mycobacterium tuberculosis ; MDR-TB ; XDR-TB ; 5 ; 6-Fused heteroaromatics ; Imidazo[1 ; 2-a]pyridine
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 April, 2012
• 卷：20
• 期：7
• 页码：2214-2220
• 文件大小：584 K

摘要

Tuberculosis (TB) is a devastating disease resulting in a death every 20 s. Thus, new drugs are urgently needed. Herein we report ten classes of compounds鈥攐xazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole, imidazo[1,2-m>am>]pyridine, imidazo[1,2-m>am>]pyrimidine and imidazo[1,2-m>cm>]pyrimidine鈥攚hich have good (micromolar) to excellent (sub-micromolar) antitubercular potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC鈥檚 as low as <0.195 渭M (dFont">9 and dFont">11). Overall, the imidazo[1,2-m>am>]pyridine class was determined to be most promising, with potency similar to isoniazid and PA-824 against replicating m>Mtbm> H₃₇Rv, clinically relevant drug sensitive, multi- and extensively resistant m>Mtbm> strains as well as having good in vitro metabolic stability.