The discovery of acylated beta-amino acids as potent and orally bioavailable VLA-4 antagonists

Bioorg Med Chem Lett. 2002 Feb 25;12(4):611-4. doi: 10.1016/s0960-894x(01)00818-6.

Abstract

Acylated beta-amino acids are described as potent, specific and orally bioavailable antagonists of VLA-4. The initial lead was identified from a combinatorial library. Subsequent optimization using a traditional medicinal chemistry approach led to significant improvement in potency (up to 8-fold) while maintaining good pharmacokinetic properties.

MeSH terms

  • Acylation
  • Administration, Oral
  • Amino Acids / chemical synthesis*
  • Amino Acids / metabolism
  • Amino Acids / pharmacokinetics
  • Animals
  • Biological Availability
  • Combinatorial Chemistry Techniques
  • Drug Evaluation, Preclinical
  • Inflammation Mediators / chemical synthesis*
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / pharmacokinetics
  • Integrin alpha4beta1 / antagonists & inhibitors*
  • Metabolic Clearance Rate
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Inflammation Mediators
  • Integrin alpha4beta1