A new chemotype with promise against Trypanosoma cruzi. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: Wang, Xiaofang; Cal, Monica; Kaiser, Marcel; Buckner, Frederick S.; Lepesheva, Galina I.; Sanford, Austin G.; Wallick, Alexander I.; Davis, Paul H.; Vennerstrom, Jonathan L.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 1(2020)
• Publication Date: 2020-01-01
• Subjects: Chagas disease -- Trypanosoma cruzi -- SAR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.126778
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure–activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N -methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi . Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.