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SAR of a new antischistosomal urea carboxylic acid

Wu, Jianbo and Wang, Chunkai and Häberli, Cécile and White, Karen L. and Shackleford, David M. and Chen, Gong and Dong, Yuxiang and Charman, Susan A. and Keiser, Jennifer and Vennerstrom, Jonathan L.. (2018) SAR of a new antischistosomal urea carboxylic acid. Bioorganic & medicinal chemistry letters, 28 (23-24). pp. 3648-3651.

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Official URL: https://edoc.unibas.ch/67936/

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Abstract

Urea carboxylic acids, products of aryl hydantoin hydrolysis, were recently identified as a new antischistosomal chemotype. We now describe a baseline structure-activity relationship (SAR) for this compound series. With one exception, analogs of lead urea carboxylic acid 2 were quite polar with Log D; 7.4; values ranging from -1.9 to 1.8, had high aqueous solubilities in the range of 25-100 µg/mL, and were metabolically stable. None of the compounds had measurable in vitro antischistosomal activity or cytotoxicity, but four of these had moderate worm burden reduction (WBR) values of 42-70% when they were administered as single 100 mg/kg oral doses to S. mansoni-infected mice. These data indicate that with the exception of the gem-dimethyl substructure and the distal nitrogen atom of the urea functional group, the rest of the structure of 2 is required for in vivo antischistosomal activity.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Keiser, Jennifer and Häberli, Cécile
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0960-894X
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:15 Jan 2019 15:32
Deposited On:15 Jan 2019 15:32

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