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

Bioorg Med Chem Lett. 2000 Apr 17;10(8):729-33. doi: 10.1016/s0960-894x(00)00089-5.

Abstract

A series of N-(N-benzylpyroglutamyl)-4-substituted-L-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. Analogues substituted by electron deficient benzoylamino groups bearing bulky ortho substituents had low-nM potency in an ELISA assay and low-microM activity in a cell based assay.

MeSH terms

  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Integrin alpha4beta1
  • Integrins / antagonists & inhibitors*
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / chemistry
  • Phenylalanine / pharmacology
  • Receptors, Lymphocyte Homing / antagonists & inhibitors*
  • Recombinant Proteins / antagonists & inhibitors
  • Structure-Activity Relationship
  • Vascular Cell Adhesion Molecule-1 / drug effects*

Substances

  • Integrin alpha4beta1
  • Integrins
  • Receptors, Lymphocyte Homing
  • Recombinant Proteins
  • Vascular Cell Adhesion Molecule-1
  • Phenylalanine