title: Non-peptide cholecystokinin-B/gastrin receptor antagonists based on bicyclic, heteroaromatic skeletons.
abstract: A series of potent and selective cholecystokinin-B/gastrin receptor antagonists based on the dibenzobicyclo[2.2.2]octane (BCO) skeleton which have recently been described were found to show species-dependent behavior when examined in rat and dog models. We now report the discovery of compounds in which the BCO skeleton has been replaced with bicyclic, heteroaromatic frameworks, such as a 5,6-disubstituted indole or benzimidazole. These new ligands maintain the affinity and selectivity profile of the previous compounds in vitro but show a much more consistent behavior pattern in vivo. Representative examples of this class of compound have been shown to inhibit pentagastrin-stimulated acid secretion when administered intravenously at doses of 0.1 mumol kg-1 or less.
authors.affiliation: James Black Foundation, London, U.K.
authors.forename: S B
authors.initials: SB
authors.lastname: Kalindjian
authors.forename: I M
authors.initials: IM
authors.lastname: Buck
authors.forename: J M
authors.initials: JM
authors.lastname: Davies
authors.forename: D J
authors.initials: DJ
authors.lastname: Dunstone
authors.forename: M L
authors.initials: ML
authors.lastname: Hudson
authors.forename: C M
authors.initials: CM
authors.lastname: Low
authors.forename: I M
authors.initials: IM
authors.lastname: McDonald
authors.forename: M J
authors.initials: MJ
authors.lastname: Pether
authors.forename: K I
authors.initials: KI
authors.lastname: Steel
authors.forename: M J
authors.initials: MJ
authors.lastname: Tozer
authors.forename: J G
authors.initials: JG
authors.lastname: Vinter
mesh_terms: D000818:Animals; D004285:Dogs; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013045:Species Specificity
chemical_list: D011083:Polycyclic Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C096271:dibenzobicyclo(2.2.2)octane