Development of 1,4-benzodiazepine cholecystokinin type B antagonists

J Med Chem. 1993 Dec 24;36(26):4276-92. doi: 10.1021/jm00078a018.


A series of 3-(arylureido)-5-phenyl-1,4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), are described. Derived by reasoned modification of the CCK-A selective 3-carboxamido-1,4-benzodiazepine, MK-329, this paper chronicles the development of potent, orally effective compounds in which selectivity for the CCK-B receptor subtype was achieved. The principal lead structure that emerged from these studied is L-365,260, a compound which has been submitted for clinical evaluation. Details of the ability to modulate the receptor interactions of these benzodiazepines by appropriate structure modifications are discussed which imply the possibility of further refining the CCK-B receptor affinity and selectivity of this class of compounds.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzodiazepines / chemical synthesis*
  • Benzodiazepines / pharmacokinetics
  • Benzodiazepines / pharmacology
  • Benzodiazepinones / chemical synthesis*
  • Benzodiazepinones / chemistry
  • Benzodiazepinones / pharmacokinetics
  • Benzodiazepinones / pharmacology
  • Biological Availability
  • Cerebral Cortex / metabolism
  • Devazepide
  • Guinea Pigs
  • Molecular Structure
  • Pancreas / metabolism
  • Phenylurea Compounds*
  • Rats
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Sincalide / metabolism
  • Structure-Activity Relationship


  • Benzodiazepinones
  • Phenylurea Compounds
  • Receptors, Cholecystokinin
  • Benzodiazepines
  • L 365260
  • Devazepide
  • Sincalide