Discovery and SAR of diarylsulfide cyclopropylamide LFA-1/ICAM-1 interaction antagonists

Bioorg Med Chem Lett. 2001 Apr 23;11(8):973-6. doi: 10.1016/s0960-894x(01)00105-6.

Abstract

Diarylsulfide cyclopropylamides were synthesized and evaluated as LFA-1/ICAM-1 interaction antagonists. A substituent pattern was identified which maximized potency and minimized protein binding as exemplified by antagonist 30 (IC50 = 5 nM).

MeSH terms

  • Administration, Oral
  • Amides / chemical synthesis
  • Amides / pharmacology*
  • Animals
  • Area Under Curve
  • Biological Availability
  • Cell Communication / drug effects*
  • Cell Communication / physiology
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / pharmacology*
  • Endothelium / cytology
  • Endothelium / metabolism
  • Inhibitory Concentration 50
  • Intercellular Adhesion Molecule-1 / drug effects*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukocytes / metabolism
  • Lymphocyte Function-Associated Antigen-1 / drug effects*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Protein Binding / physiology
  • Rats
  • Structure-Activity Relationship

Substances

  • Amides
  • Cyclopropanes
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1