Improving the Affinity and Selectivity of a Nonpeptide Series of Cholecystokinin-B/Gastrin Receptor Antagonists Based on the Dibenzobicyclooctane Skeleton

Article abstract of DOI:10.1021/jm00021a019

We have recently described a novel series of nonpeptidic cholecystokinin-B (CCK_B)/gastrin receptor antagonists based on a dibenzobicyclo<2.2.2>octane skeleton.We wish now to report on compounds arising out of our earlier work which have substantially greater affinity as antagonists for the CCK_B/gastrin receptor system and which maintain, or improve on, the already high selectivity with respect to CCK_A receptors.Thus, cis-7-<<<(1S)-<<(3,5-dicarboxy-phenyl)amino>carbonyl>-2-phenylethyl>amino>carbonyl>-8-<<(1-adamantylmethyl)amino>-carbonyl>-2,3:5,6-dibenzobicyclo<2.2.2)octane expressed a pK_i of 8.80 in mouse cortical membranes at CCK_B/gastrin receptors.THe selectivity for these receptors over CCK_A receptors was in the order of 1000-fold.