Specific and dual antagonists of alpha(4)beta(1) and alpha(4)beta(7) integrins

Bioorg Med Chem Lett. 2002 Jan 21;12(2):133-6. doi: 10.1016/s0960-894x(01)00705-3.

Abstract

N-(3,5-Dichlorophenylsulfonyl)-(R)-thioprolyl biarylalanine 10a has been identified as a potent and specific antagonist of the alpha(4)beta(1) integrin. Altering the configuration of thioproline from R to S led to a series of dual antagonists of alpha(4)beta(1) and alpha(4)beta(7), and the N-acetyl analogue 8b was found to be the most potent dual antagonist. A binding site model for alpha(4)beta(1) and alpha(4)beta(7) is proposed to explain the structure-activity relationship.

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / chemistry
  • Alanine / pharmacology*
  • Integrin alpha4beta1
  • Integrins / antagonists & inhibitors*
  • Receptors, Lymphocyte Homing / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology*

Substances

  • Integrin alpha4beta1
  • Integrins
  • N-(3,5-dichlorophenylsulfonyl)-thioprolyl biarylalanine
  • Receptors, Lymphocyte Homing
  • Sulfhydryl Compounds
  • integrin alpha4beta7
  • Alanine