Piperidine-containing beta-arylpropionic acids as potent antagonists of alphavbeta3/alphavbeta5 integrins

Bioorg Med Chem Lett. 2004 Oct 18;14(20):5227-32. doi: 10.1016/j.bmcl.2004.06.061.

Abstract

The synthesis and SAR of a new class of piperidine-based alphavbeta3/alphavbeta5 integrin antagonists is described. Replacement of an amide bond in a prototype isonipecotamide by a C-C isostere, and adjustment of the spacer length between the carboxylic acid and basic moieties, led to low nanomolar antagonists of alphavbeta3 and/or alphavbeta5 integrins with excellent selectivity versus alpha(IIb)beta3.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Integrin alphaVbeta3 / metabolism
  • Integrins / antagonists & inhibitors*
  • Integrins / metabolism
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Propionates / chemical synthesis*
  • Propionates / chemistry
  • Propionates / pharmacology
  • Protein Binding
  • Rats
  • Receptors, Vitronectin / antagonists & inhibitors*
  • Receptors, Vitronectin / metabolism
  • Structure-Activity Relationship

Substances

  • Integrin alphaVbeta3
  • Integrins
  • Piperidines
  • Propionates
  • Receptors, Vitronectin
  • integrin alphaVbeta5