Diamine containing VLA-4 antagonists

Bioorg Med Chem. 2001 Aug;9(8):2195-202. doi: 10.1016/s0968-0896(01)00132-8.

Abstract

Design and synthesis of a library as potential VLA-4 antagonists has been accomplished, based around a proposed pharmacophoric model. Compounds possessing submicromolar potency were identified and structure-activity relationships were seen across the library. Further derivatisation produced compounds with IC(50)'s <10 nmol for inhibiting the VLA-4 mediated binding of fibronectin to RAMOS cells, providing an ideal starting point for a lead optimisation Programme.

MeSH terms

  • Cell Adhesion / drug effects
  • Diamines / chemical synthesis*
  • Diamines / chemistry
  • Diamines / pharmacology
  • Drug Design
  • Humans
  • Integrin alpha4beta1
  • Integrins / antagonists & inhibitors*
  • Integrins / chemistry
  • Receptors, Lymphocyte Homing / antagonists & inhibitors*
  • Receptors, Lymphocyte Homing / chemistry
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Diamines
  • Integrin alpha4beta1
  • Integrins
  • Receptors, Lymphocyte Homing