7 substituted 2 Nitro-5,6-dihydroimidazo[2,1 b][1,3]oxazines: novel antitubercular agents lead to a new preclinical candidate for visceral leishmaniasis

by Thompson A, O’Connor PD, Marshall AJ, Yardley V,  Maes L, Gupta S, Launay D, Braillard S, Chatelain E, Franzblau SG, Wan B, Wang Y, Ma Z, Cooper CB, Denny WA. Journal of Medicinal Chemistry 2017, doi: 10.1371/journal.pntd.0005635.

Summary: Within a backup program for the clinical investigational agent pretomanid, scaffold hopping from delamanid inspired the discovery of a novel class of potent antitubercular agents that unexpectedly possessed notable utility against the kinetoplastid disease visceral leishmaniasis (VL). Following the identification of delamanid analogue DNDI-VL-2098 as a VL preclinical candidate, this structurally related 7- substituted 2-nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazine class was further explored, seeking efficacious backup compounds with improved solubility and safety. This investigation has revealed that the 7-substituted 2-nitroimidazooxazine class has exciting potential to treat up to three neglected diseases and can deliver drug candidates that are worthy of examination in ongoing studies.

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