3-[2-(N-phenylacetamide)]-1,5-benzodiazepines: orally active, binding selective CCK-A agonists

J Med Chem. 1996 Jul 19;39(15):3030-4. doi: 10.1021/jm960205b.

Abstract

A series of modifications were made to the C-3 substituent of the 1,5-benzodiazepine CCK-A agonist 1. Replacement of the inner urea NH and addition of a methyl group to generate a C-3 quaternary carbon resulted in acetamide 6, which showed CCK-A receptor binding selectivity and sub-micromolar agonist activity in vitro. Benzodiazepine 6 was active in an in vivo mouse gallbladder emptying assay and represents a novel orally active, binding selective CCK-A agonist.

MeSH terms

  • Acetanilides*
  • Animals
  • Azepines / chemical synthesis*
  • Azepines / metabolism
  • Azepines / pharmacology
  • Cholecystokinin / agonists*
  • Gallbladder / drug effects
  • Gallbladder / physiology
  • Guinea Pigs
  • Mice
  • Molecular Structure
  • Muscle Contraction / drug effects
  • Receptors, Cholecystokinin / metabolism

Substances

  • 2-(2,4-dioxo-5-phenyl-3-methyl-3-((phenylcarbamoyl)methyl)-2,3,4,5-tetrahydrobenzo(b)(1,5)diazepin-1-yl)-N-isopropyl-N-phenylacetamide
  • Acetanilides
  • Azepines
  • Receptors, Cholecystokinin
  • Cholecystokinin