IMPROVING THE AFFINITY AND SELECTIVITY OF A NONPEPTIDE SERIES OF CHOLECYSTOKININ-B GASTRIN RECEPTOR ANTAGONISTS BASED ON THE DIBENZOBICYCLO[2.2.2]OCTANE SKELETON/

We have recently described a novel series of nonpeptidic cholecystokin in-B (CCKB)/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 antagoni sts for the CCKB/gastrin receptor system and which maintain, or improv e on, the already high selectivity with respect to CCKA receptors. Thu s, mino]-carbonyl-2,3:5,6-dibenzobicyclo[2.2.2]octane expressed a pK(i ) of 8.80 in mouse cortical membranes at CCKB/gastrin receptors. The s electivity for these receptors over CCKA receptors was in the order of 1000-fold.