Document Report Card

ID: ALA1129562

Journal: J Med Chem

Title: Non-peptide cholecystokinin-B/gastrin receptor antagonists based on bicyclic, heteroaromatic skeletons.

Authors: Kalindjian SB, Buck IM, Davies JM, Dunstone DJ, Hudson ML, Low CM, McDonald IM, Pether MJ, Steel KI, Tozer MJ, Vinter JG.

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.

CiteXplore: 8627604

DOI: 10.1021/jm9508907