Abstract
A series of 5-phenyl-3-ureidobenzodiazepine-2,4-diones was synthesized and evaluated as cholecystokinin-B (CCK-B) receptor antagonists. Structure-activity relationship (SAR) studies revealed the importance of the N-1 substituent for potent and selective CCK-B affinity. Addition of substituents at the urea side chain provided in some cases more potent compounds. Moreover the introduction of bulky substituents such as adamantylmethyl at N-1 and resolution of the racemic ureas resulted in our lead compound GV150013.
MeSH terms
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Animals
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Anti-Anxiety Agents / chemical synthesis*
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Anti-Anxiety Agents / chemistry
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Anti-Anxiety Agents / pharmacology
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Benzodiazepines / chemical synthesis*
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Benzodiazepines / chemistry
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Benzodiazepines / pharmacology
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Callithrix
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Cerebral Cortex / metabolism
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Crystallography, X-Ray
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Guinea Pigs
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HeLa Cells
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Humans
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In Vitro Techniques
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Membranes
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Mice
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Models, Molecular
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Pancreas / metabolism
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Radioligand Assay
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Rats
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Receptor, Cholecystokinin A
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Receptor, Cholecystokinin B
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Receptors, Cholecystokinin / antagonists & inhibitors*
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Receptors, Cholecystokinin / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Anti-Anxiety Agents
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Receptor, Cholecystokinin A
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Receptor, Cholecystokinin B
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Receptors, Cholecystokinin
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Benzodiazepines