title: 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-[(2S,4R)-methyl-6-phenyl-2,4-dihydro-1H-imidazo[1,2- alpha][1,4]benzodiazepin-4-yl]-N'-[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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486.
authors.forename: M G
authors.initials: MG
authors.lastname: Bock
authors.forename: R M
authors.initials: RM
authors.lastname: DiPardo
authors.forename: R C
authors.initials: RC
authors.lastname: Newton
authors.forename: J M
authors.initials: JM
authors.lastname: Bergman
authors.forename: D F
authors.initials: DF
authors.lastname: Veber
authors.forename: S B
authors.initials: SB
authors.lastname: Freedman
authors.forename: A J
authors.initials: AJ
authors.lastname: Smith
authors.forename: K L
authors.initials: KL
authors.lastname: Chapman
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: J A
authors.initials: JA
authors.lastname: Kemp
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D008024:Ligands; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D001569:Benzodiazepines