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Cholecystokinin antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 1991 Dec; Vol. 34 (12), pp. 3350-9. - Publication Year :
- 1991
-
Abstract
- The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a novel series of benzotript-based hybrid antagonists N alpha-(3'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (9, A-67396), N alpha-(4',8'-dihydroxy-2'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (23, A-70276), and N alpha-(3'-quinolylcarbonyl)-(R)-5'-hydroxytryptophan di-n-pentylamide (36, A-71134) which possess respectively binding affinities of 23, 21, and 11 nM for the pancreatic CCK-A receptor and which inhibit CCK8-induced amylase secretion. Compound 9 possesses a selectivity of greater than 500-fold for the pancreatic CCK-A receptor over the CCK-B receptor.
- Subjects :
- Animals
Benzamides pharmacology
Binding, Competitive
Glutamates chemical synthesis
Glutamates pharmacology
Guinea Pigs
In Vitro Techniques
Receptors, Cholecystokinin metabolism
Stereoisomerism
Structure-Activity Relationship
Tryptophan chemical synthesis
Tryptophan pharmacology
Benzamides chemical synthesis
Cholecystokinin antagonists & inhibitors
Receptors, Cholecystokinin drug effects
Tryptophan analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 34
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 1766000
- Full Text :
- https://doi.org/10.1021/jm00116a002