A new chemotype with promise against Trypanosoma cruzi

[Display omitted] 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...

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Published inBioorganic & medicinal chemistry letters Vol. 30; no. 1; p. 126778
Main 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.
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier Ltd 01.01.2020
Elsevier
Subjects
Animals
Chagas disease
Chagas Disease - drug therapy
Chemistry
Chemistry, Medicinal
Chemistry, Organic
Humans
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Physical Sciences
SAR
Science & Technology
Structure-Activity Relationship
Trypanocidal Agents - pharmacology
Trypanocidal Agents - therapeutic use
Trypanosoma cruzi
Trypanosoma cruzi - drug effects
Chagas disease
SAR
Trypanosoma cruzi
SUBSTRATE
DRUG DISCOVERY
CYP51
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Summary:[Display omitted] 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2019.126778