N-(arylacetyl)-biphenylalanines as potent VLA-4 antagonists

Bioorg Med Chem Lett. 2002 Aug 19;12(16):2141-4. doi: 10.1016/s0960-894x(02)00366-9.

Abstract

A series of potent N-(aralkyl-, arylcycloalkyl-, and heteroaryl-acyl)-4-biphenylalanine VLA-4 antagonists was prepared by rapid analogue methods using solid-phase chemistry. Further optimization led to several highly potent compounds (IC(50) <1 nM). Evaluation of rat pharmacokinetic revealed generally high clearance.

MeSH terms

  • Animals
  • Binding Sites
  • Inhibitory Concentration 50
  • Integrin alpha4beta1 / antagonists & inhibitors*
  • Molecular Structure
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / chemical synthesis*
  • Phenylalanine / pharmacokinetics
  • Phenylalanine / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Integrin alpha4beta1
  • Phenylalanine