Conformationally restricted analogues of the potent CCK-B antagonist CI-988.
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.
Higginbottom
M
M
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, U.K.
Hill
D R
DR
Horwell
D C
DC
Mostafai
E
E
Suman-Chauhan
N
N
Roberts
E
E
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
D007211:Indoles; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D008536:Meglumine