Nonpeptide alpha V beta 3 antagonists. Part 9: Improved pharmacokinetic profile through the use of an aliphatic, des-amide backbone

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4411-5. doi: 10.1016/j.bmcl.2004.06.068.

Abstract

A series of alphaVbeta3 receptor antagonists lacking the amide bond of previously-reported 'chain-shortened' compounds is described. Replacement of the lone amide bond with two methylene groups in this series yields more lipophilic compounds that have longer half-lives, lower clearance, and greater oral bioavailability when administered to dogs.

MeSH terms

  • Animals
  • Benzenesulfonates / chemistry*
  • Benzenesulfonates / pharmacokinetics*
  • Dogs
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Integrin alphaVbeta3 / metabolism
  • Iodobenzenes / chemistry*
  • Iodobenzenes / pharmacokinetics*

Substances

  • Benzenesulfonates
  • Integrin alphaVbeta3
  • Iodobenzenes
  • benzenesulfonic acid