The synthesis and evaluation of triazolopyrimidines as anti-tubercular agents

Publication date: Available online 19 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Edison S. Zuniga, Aaron Korkegian, Steven Mullen, Erik J. Hembre, Paul L. Ornstein, Guillermo Cortez, Kallolmay Biswas, Naresh Kumar, Jeffrey Cramer, Thierry Masquelin, Philip A. Hipskind, Joshua Odingo, Tanya Parish
We identified a di-substituted triazolopyrimidine with anti-tubercular activity against Mycobacterium tuberculosis. Three segments of the scaffold were examined rationally to establish a structure-activity relationship with the goal of improving potency and maintaining good physicochemical properties. A number of compounds displayed sub-micromolar activity against Mycobacterium tuberculosis with no cytotoxicity against eukaryotic cells. Non-substituted aromatic rings at C5 and a two-carbon chain connecting a terminal aromatic at C7 were preferred features; the presence of NH at C7 and a lack of substituent at C2 were essential for potency. We identified compounds with acceptable metabolic stability in rodent and human liver microsomes. Our findings suggest that the easily-synthesized triazolopyrimidines are a promising class of potent anti-tubercular agents and warrant further investigation in our search for new drugs to fight tuberculosis.

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