N-Benzoyl amino acids as LFA-1/ICAM inhibitors 1: amino acid structure-activity relationship

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1015-8. doi: 10.1016/s0960-894x(03)00084-2.

Abstract

The association of ICAM-1 with LFA-1 plays a critical role in several autoimmune diseases. N-2-Bromobenzoyl L-tryptophan, compound 1, was identified as an inhibitor to the formation of the LFA-1/ICAM complex. The SAR of the amino acid indicates that the carboxylic acid is required for inhibition and that L-histidine is the most favored amino acid.

MeSH terms

  • Amino Acids / chemical synthesis
  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Histidine / chemistry
  • Histidine / pharmacology
  • Indicators and Reagents
  • Intercellular Adhesion Molecule-1 / drug effects*
  • Lymphocyte Function-Associated Antigen-1 / drug effects*
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Carboxylic Acids
  • Indicators and Reagents
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1
  • Histidine