Optimization of Orally Bioavailable Antileishmanial 2,4,5-Trisubstituted Benzamides.

ABSTRACT: Leishmaniasis, a neglected tropical disease caused by Leishmania species parasites, annually affects over 1 million individuals worldwide. Treatment options for leishmaniasis are limited due to high cost, severe adverse effects, poor efficacy, difficulty of use, and emerging drug resistance to all approved therapies. We discovered 2,4,5-trisubstituted benzamides (4) that possess potent antileishmanial activity but poor aqueous solubility. Herein, we disclose our optimization of the physicochemical and metabolic properties of 2,4,5-trisubstituted benzamide that retains potency. Extensive structure-activity and structure-property relationship studies allowed selection of early leads with suitable potency, microsomal stability, and improved solubility for progression. Early lead

SUBMITTER: Kim HS 

PROVIDER: S-EPMC10259451 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature