N-Aroyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2479-82. doi: 10.1016/s0960-894x(02)00387-6.

Abstract

A series of N-benzoyl-4-[(2,6-dichlorobenzoyl)amino]-L-phenylalanine derivatives was prepared in order to optimize the substitution on the N-benzoyl moiety for VCAM/VLA-4 antagonist activity. Disubstitution in the 2- and 6-positions is favored and a range of small alkyl and halogen are tolerated. A model of the bioactive conformation of these compounds is proposed.

MeSH terms

  • Heterocyclic Compounds / chemistry
  • Humans
  • Hydrocarbons, Aromatic
  • Inhibitory Concentration 50
  • Integrin alpha4beta1 / antagonists & inhibitors*
  • Models, Molecular
  • Molecular Mimicry
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology
  • Protein Binding
  • Structure-Activity Relationship
  • Vascular Cell Adhesion Molecule-1 / drug effects*

Substances

  • Heterocyclic Compounds
  • Hydrocarbons, Aromatic
  • Integrin alpha4beta1
  • Vascular Cell Adhesion Molecule-1
  • Phenylalanine