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The synthesis and evaluation of triazolopyrimidines as anti-tubercular agents

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 propertie...

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Detalles Bibliográficos
Autores principales: Zuniga, Edison S., Korkegian, Aaron, Mullen, Steven, Hembre, Erik J., Ornstein, Paul L., Cortez, Guillermo, Biswas, Kallolmay, Kumar, Naresh, Cramer, Jeffrey, Masquelin, Thierry, Hipskind, Philip A., Odingo, Joshua, Parish, Tanya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513444/
https://www.ncbi.nlm.nih.gov/pubmed/28576632
http://dx.doi.org/10.1016/j.bmc.2017.05.030
Descripción
Sumario: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.