N-Tetrahydrofuroyl-(L)-phenylalanine derivatives as potent VLA-4 antagonists

Bioorg Med Chem Lett. 2002 Jun 3;12(11):1497-500. doi: 10.1016/s0960-894x(02)00210-x.

Abstract

Given the proposed involvement of VLA-4 in inflammatory processes, a program to identify orally active VLA-4 antagonists was initiated. Herein, we report the discovery of a N-tetrahydrofuroyl-(L)-phenylalanine derivative (17) and related analogues as potent VLA-4 antagonists with good oral bioavailability.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Binding Sites
  • Biological Availability
  • Dose-Response Relationship, Drug
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacokinetics
  • Furans / pharmacology
  • Half-Life
  • Inhibitory Concentration 50
  • Integrin alpha4beta1 / antagonists & inhibitors*
  • Macaca mulatta
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / chemical synthesis
  • Phenylalanine / pharmacokinetics
  • Phenylalanine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / pharmacology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Furans
  • Integrin alpha4beta1
  • Sulfonamides
  • Vascular Cell Adhesion Molecule-1
  • tetrahydrofuran
  • Phenylalanine