New Class of Antitrypanosomal Agents Based on Imidazopyridines.

ABSTRACT: The present work describes the synthesis of 22 new imidazopyridine analogues arising from medicinal chemistry optimization at different sites on the molecule. Seven and 12 compounds exhibited an in vitro EC₅₀ ≤ 1 μM against Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) parasites, respectively. Based on promising results of in vitro activity (EC₅₀ < 100 nM), cytotoxicity, metabolic stability, protein binding, and pharmacokinetics (PK) properties, compound 20 was selected as a candidate for in vivo efficacy studies. This compound was screened in an acute mouse model against T.cruzi (Tulahuen strain). After established infection, mice were dosed twice a day for 5 days, and then monitored for

SUBMITTER: Silva DG 

PROVIDER: S-EPMC5512129 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature