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

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2475-8. doi: 10.1016/s0960-894x(02)00386-4.

Abstract

A systematic structure-activity relationship investigation of the lead compound 1 resulted the identification of several N-[(substituted alkyl)cycloalkanoyl]-4-[((2,6-dichlorophenyl)carbonyl)amino]-L-phenylalanine derivatives as potent VCAM/VLA-4 antagonists. The data are consistent with a model of these compounds in which these alkanoylphenylalanines reside in a compact gauche (-) bioactive conformation.

MeSH terms

  • Crystallography, X-Ray
  • Cycloparaffins / chemical synthesis
  • Cycloparaffins / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Integrin alpha4beta1 / antagonists & inhibitors*
  • Molecular Structure
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology
  • Protein Binding
  • Structure-Activity Relationship
  • Vascular Cell Adhesion Molecule-1 / drug effects*

Substances

  • Cycloparaffins
  • Integrin alpha4beta1
  • Vascular Cell Adhesion Molecule-1
  • Phenylalanine