SAR of a new antischistosomal urea carboxylic acid

Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3648-3651. doi: 10.1016/j.bmcl.2018.10.039. Epub 2018 Oct 25.


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.

Keywords: Antischistosomal; SAR; Urea carboxylic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carboxylic Acids / chemistry*
  • Carboxylic Acids / metabolism
  • Carboxylic Acids / pharmacology
  • Carboxylic Acids / therapeutic use
  • Half-Life
  • Humans
  • Mice
  • Microsomes, Liver / metabolism
  • Schistosoma mansoni / drug effects
  • Schistosomiasis mansoni / drug therapy
  • Schistosomiasis mansoni / veterinary
  • Schistosomicides / chemistry*
  • Schistosomicides / metabolism
  • Schistosomicides / pharmacology
  • Schistosomicides / therapeutic use
  • Structure-Activity Relationship
  • Urea / chemistry*


  • Carboxylic Acids
  • Schistosomicides
  • Urea