IMPROVING THE AFFINITY AND SELECTIVITY OF A NONPEPTIDE SERIES OF CHOLECYSTOKININ-B GASTRIN RECEPTOR ANTAGONISTS BASED ON THE DIBENZOBICYCLO[2.2.2]OCTANE SKELETON/
Sb. Kalindjian et al., IMPROVING THE AFFINITY AND SELECTIVITY OF A NONPEPTIDE SERIES OF CHOLECYSTOKININ-B GASTRIN RECEPTOR ANTAGONISTS BASED ON THE DIBENZOBICYCLO[2.2.2]OCTANE SKELETON/, Journal of medicinal chemistry, 38(21), 1995, pp. 4294-4302
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.