title: Cholecystokinin antagonists. Synthesis of asperlicin analogues with improved potency and water solubility.
abstract: Seventeen analogues of the selective, competitive cholecystokinin (CCK) antagonist asperlicin 1 were prepared. These compounds were tested as inhibitors of the binding of [125I]CCK to rat pancreas and guinea pig brain receptors. Compounds 4, 7, and 8 were more potent than asperlicin on the pancreatic CCK receptor. One analogue, 17, displayed potency equivalent to asperlicin on the pancreas CCK receptor and showed a marked improvement in aqueous solubility, thereby facilitating the use of this class of CCK antagonists in physiological and pharmacological studies.
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; C046367:asperlicin