Structure-activity relationships of 1,5-dihydro-2<i>H</i>-benzo[<i>b</i>][1,4]diazepine-2,4(3<i>H</i>)-diones as inhibitors of <i>Trypanosoma cruzi</i>.

ABSTRACT: Chagas disease, caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi), is responsible for a large health burden with around 6-8 million people infected globally. The current drug development pipeline is sparsely populated and there is an urgent need for new treatments. In this paper we describe the identification of a series of benzodiazepinediones with antiparasitic activity, and the platform we utilised to demonstrate that they act via a novel mechanism of action. Two distinct sub-series were identified, and the medicinal chemistry program identified compounds from both with pIC₅₀'s >6.4 which were progressed to a T. cruzi washout assay. This assay showed that neither sub-series was suitable for further development. This work

SUBMITTER: Thomas MG 

PROVIDER: S-EPMC12208134 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature