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

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Dichiara, Maria ; Simpson, Quillon J. ; Quotadamo, Antonio ; Jalani, Hitesh B. ; Huang, Anson X. ; Millard, Caroline C. ; Klug, Dana M. ; Tse, Edwin G. ; Todd, Matthew H. ; Silva, Daniel Gedder ; Emery, Flavio da Silva ; Carlson, J. Eric ; Zheng, Shao-Liang ; Vleminckx, Margot ; Matheeussen, An ; Caljon, Guy ; Pollastri, Michael P. ; Sjo, Peter ; Perry, Benjamin ; Ferrins, Lori

• Document type: Journal article
• Source: ACS INFECTIOUS DISEASES; v. 9, n. 8, p. 18-pg., 2023-07-07.

Abstract

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. (AU)

• FAPESP's process: 21/11899-0 - Development of novel series of potent and selective heterocyclic compounds as anti-infectives agents
• Grantee: Daniel Gedder Silva
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 17/21146-4 - Heterocyclic chemistry and epigenetic for the development of library of compounds for medicinal chemistry purposes.
• Grantee: Flavio da Silva Emery
• Support Opportunities: Regular Research Grants