Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists II: tuning of receptor selectivity and in vivo efficacy

Bioorg Med Chem Lett. 2009 Nov 15;19(22):6376-8. doi: 10.1016/j.bmcl.2009.09.065. Epub 2009 Sep 23.

Abstract

In the previous article we demonstrated how certain CCK2R-selective anthranilic amides could be structurally modified to afford high-affinity, selective CCK1R activity. We now describe our efforts at modulating and optimizing the CCK1R and CCK2R affinities aimed at producing compounds with good pharmacokinetics properties and in vivo efficacy in rat models of gastric acid and pancreatic amylase secretion.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Isoxazoles / chemistry*
  • Models, Molecular
  • Rats
  • Rats, Wistar
  • Receptor, Cholecystokinin A / antagonists & inhibitors*
  • Receptor, Cholecystokinin B / antagonists & inhibitors*
  • Signal Transduction / drug effects*
  • Sulfonamides / pharmacology*
  • Treatment Outcome

Substances

  • Isoxazoles
  • Receptor, Cholecystokinin A
  • Receptor, Cholecystokinin B
  • Sulfonamides
  • anthranil