title: Conformationally restricted analogues of the potent CCK-B antagonist CI-988.
abstract: The synthesis and structure-activity relationships (SAR) for a series of conformationally restricted analogues of the selective cholecystokinin (CCK) antagonist CI-988 and some closely related analogues are described. A series of appropriately substituted cis- and trans-amino decalins are prepared that mimic the through bond distances between the functional groups in the parent compound CI-988 whilst restricting bond rotation. This strategy has led to conformationally more rigid derivatives that have increased CCK-B receptor binding affinity.
authors.affiliation: Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Higginbottom
authors.forename: D R
authors.initials: DR
authors.lastname: Hill
authors.forename: D C
authors.initials: DC
authors.lastname: Horwell
authors.forename: E
authors.initials: E
authors.lastname: Mostafai
authors.forename: N
authors.initials: N
authors.lastname: Suman-Chauhan
authors.forename: E
authors.initials: E
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008536:Meglumine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D008536:Meglumine