Repositioning antitubercular 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for neglected tropical diseases: Structure-activity studies on a preclinical candidate for visceral leishmaniasis

by Thompson AM, O’Connor PD, Blaser A, Yardley V, Maes L, Gupta S, Launay D, Martin D, Franzblau SG, Wan B, Wang Y, Ma Z, Denny WA. Journal of Medicinal Chemistry 2016. 24;59(6):2530-50. doi:10.1021/acs.jmedchem.5b01699.

Summary: 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole derivatives were initially studied for tuberculosis within a backup program for the clinical trial agent pretomanid (PA-824). Phenotypic screening of representative examples against kinetoplastid diseases unexpectedly led to the identification of DNDI-VL-2098 as a potential first-in-class drug candidate for visceral leishmaniasis (VL). Additional work was then conducted to delineate its essential structural features, aiming to improve solubility and safety without compromising activity against VL.

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