Discovery of novel motilin antagonists: Conversion of tetrapeptide leads to orally available peptidomimetics

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3426-9. doi: 10.1016/j.bmcl.2009.05.059. Epub 2009 May 20.

Abstract

We successfully discovered peptidomimetic motilin antagonists (17c and 17d) through the improvement of physicochemical properties of a tetrapeptide antagonist (2). Furthermore, with oral administration and based on motilin antagonistic activity, both compounds suppressed motilin-induced colonic and gastric motility in conscious dogs.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cell Line
  • Drug Discovery
  • Gastrointestinal Agents / antagonists & inhibitors*
  • Gastrointestinal Agents / metabolism
  • Humans
  • Motilin / antagonists & inhibitors*
  • Motilin / metabolism
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Permeability
  • Rabbits
  • Rats

Substances

  • Gastrointestinal Agents
  • Oligopeptides
  • Peptides
  • Motilin