Comparison of N,N'-diarylsquaramides and N,N'-diarylureas as antagonists of the CXCR2 chemokine receptor

Bioorg Med Chem Lett. 2007 Mar 15;17(6):1713-7. doi: 10.1016/j.bmcl.2006.12.067. Epub 2006 Dec 23.

Abstract

N,N'-diarylsquaramides were prepared and evaluated as antagonists of CXCR2. The compounds were found to be potent and selective antagonists of CXCR2. Significant differences in SAR was observed relative to the previously described N,N'-diarylurea series. As was the case in the N,N'-diarylurea series, placing sulfonamide substituent adjacent to the acidic phenol significantly reduced the clearance in rat pharmacokinetic studies.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • CHO Cells
  • Chemical Phenomena
  • Chemistry, Physical
  • Cricetinae
  • Cricetulus
  • Cyclobutanes / chemical synthesis*
  • Cyclobutanes / pharmacokinetics*
  • Cyclobutanes / pharmacology*
  • Indicators and Reagents
  • Mass Spectrometry
  • Phenols / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-8B / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis*
  • Urea / pharmacokinetics*
  • Urea / pharmacology*

Substances

  • Cyclobutanes
  • Indicators and Reagents
  • Phenols
  • Receptors, Interleukin-8B
  • Sulfonamides
  • Urea