Structure-Property Optimization of a Series of Imidazopyridines for Visceral Leishmaniasis

Leishmaniasis is a collection of diseases caused by morethan 20 Leishmania parasite speciesthat manifest as eithervisceral, cutaneous, or mucocutaneous leishmaniasis. Despite the significantmortality and morbidity associated with leishmaniasis, it remainsa neglected tropical disease. Existing treatments have variable efficacy,significant toxicity, rising resistance, and limited oral bioavailability,which necessitates the development of novel and affordable therapeutics.Here, we report on the continued optimization of a series of imidazopyridinesfor visceral leishmaniasis and a scaffold hop to a series of substituted2-(pyridin-2-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles with improved absorption, distribution, metabolism,and elimination properties.

Automated summary

Leishmaniasis is a group of diseases caused by Leishmania parasites, with visceral, cutaneous, or mucocutaneous manifestations. It is a neglected tropical disease, despite its significant mortality and morbidity. Current treatments have limitations, such as variable efficacy, toxicity, resistance, and limited bioavailability, highlighting the need for novel and affordable therapeutics.