Dehydrophenylalanine derivatives as VLA-4 integrin antagonists

Bioorg Med Chem Lett. 2003 Mar 10;13(5):805-8. doi: 10.1016/s0960-894x(03)00019-2.

Abstract

We describe a series of dehydrophenylalanine derivatives where the Z isomers are potent VLA-4 antagonists but are subject to rapid biliary clearance and the E isomers have poor activity but have a slower rate of clearance. These configurationally constrained molecules have led to the design of a novel class of benzodiazepine VLA-4 antagonists.

MeSH terms

  • Animals
  • Benzodiazepines / chemistry
  • Benzodiazepines / pharmacology
  • Biliary Tract / metabolism
  • Drug Design
  • Inhibitory Concentration 50
  • Integrin alpha4beta1 / antagonists & inhibitors*
  • Isomerism
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / chemistry*
  • Phenylalanine / pharmacokinetics
  • Phenylalanine / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Integrin alpha4beta1
  • Benzodiazepines
  • Phenylalanine
  • phenyldehydroalanine