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SAR of a new antischistosomal urea carboxylic acid.

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?D7.4 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.

SUBMITTER: Wu J

PROVIDER: S-EPMC6301076 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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SAR of a new antischistosomal urea carboxylic acid.

Wu Jianbo J Wang Chunkai C Häberli Cécile C White Karen L KL Shackleford David M DM Chen Gong G Dong Yuxiang Y Charman Susan A SA Keiser Jennifer J Vennerstrom Jonathan L JL

Bioorganic & medicinal chemistry letters 20181025 23-24

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<sub>7.4</sub> 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 antischistosom ...[more]

PMID: 30389288

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SAR of a new antischistosomal urea carboxylic acid.

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SAR of a new antischistosomal urea carboxylic acid.

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