Novel glutamic acid-derived cholecystokinin receptor ligands

Abstract

Novel aryl amide analogues of glutamic acid dialkylamide have been synthesized to test for a possible structural analogy between glutamic acid and benzodiazepine CCK antagonists such as compounds 2 and 24 (lorglumide and MK-329, respectively). In support of the structural model, certain of these hybrid compounds are more potent in pancreas CCK radioligand binding assays than corresponding lorglumide-type reference compounds. Modifications previously found in the benzodiazepine antagonists to result in brain CCK/gastrin receptor selectivity were also incorporated to produce an aryl urea series of glutamic acid analogues. None of these compounds were brain CCK/gastrin selective; however, one was potent and selective in the pancreas binding assay. The model appears to be most useful in the design of selective ligands for the pancreas type CCK receptor.