Selective non-peptide ligands for an accommodating peptide receptor. Imidazobenzodiazepines as potent cholecystokinin type B receptor antagonists.

Abstract A series of imidazobenzodiazepines, non-peptide antagonists of the peptide hormone cholecystokinin (CCK), are described. Derived by chemical modification of the benzodiazepine ring system embedded within the CCK-B antagonist L-365,260, these compounds display CCK-B/CCK-A selectivity and some analogs have receptor binding affinities in the subnanomolar range. This group of novel imidazobenzodiazepines, among which N -[(2 S ,4 R )-methyl-6-phenyl-2,4-dihydro-1 H -imidazo[1,2- a ][1,4] benzodiazepin-4-yl]- Ń -[3-methylphenyl]-urea ( 12 ) is the principal compound, expands the structural diversity of the collection of non-peptide CCK-B antagonists and will be useful in further delineating the function of CCK in the central nervous system.