Phenylbutyrates as potent, orally bioavailable vitronectin receptor (integrin alphavbeta3) antagonists

Bioorg Med Chem Lett. 2003 Apr 17;13(8):1483-6. doi: 10.1016/s0960-894x(03)00102-1.

Abstract

In our continuing efforts to identify small molecule vitronectin receptor antagonists, we have discovered a series of phenylbutyrate derivatives, exemplified by 16, which have good potency and excellent oral bioavailability (approximately 100% in rats). This new series is derived conceptually from opening of the seven-membered ring of SB-265123.

MeSH terms

  • Acetates / chemistry
  • Administration, Oral
  • Aminopyridines / chemistry
  • Animals
  • Biological Availability
  • Cell Adhesion / drug effects
  • Cell Line
  • Half-Life
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Phenylbutyrates / chemistry
  • Phenylbutyrates / pharmacokinetics*
  • Phenylbutyrates / pharmacology*
  • Rats

Substances

  • Acetates
  • Aminopyridines
  • Integrin alphaVbeta3
  • Phenylbutyrates
  • SB 265123