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07:41
A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
1,4-Benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonists
R G Sherrill1, J M Berman, L Birkemo
1Department of Medicinal Chemistry, Glaxo Welcome Research and Development, Research Triangle Park, NC 27709, USA. rgs13254@glaxowellcome.com
Bioorganic & Medicinal Chemistry Letters
|May 17, 2001
Summary
Researchers synthesized novel 1,4-benzodiazepines and demonstrated their cholecystokinin-A (CCK-A) agonist activity. These compounds effectively induced satiety in rats, suggesting potential therapeutic applications.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Neuroscience
Background:
- The cholecystokinin-A (CCK-A) receptor plays a crucial role in regulating satiety and gastrointestinal functions.
- Development of selective CCK-A receptor agonists is of therapeutic interest for conditions related to appetite and digestion.
Purpose of the Study:
- To synthesize and characterize a novel series of 1,4-benzodiazepine derivatives.
- To evaluate the synthesized compounds for their potential as CCK-A receptor agonists.
Main Methods:
- Synthesis of N-1-substituted 1,4-benzodiazepines featuring an N-isopropyl-N-phenylacetamide moiety.
- In vitro assessment of agonist activity using isolated guinea pig gallbladder preparations.
- In vivo evaluation of satiety induction in a rat feeding assay following intraperitoneal administration.
Main Results:
- Successful synthesis of the target 1,4-benzodiazepine series was achieved.
- Demonstrated in vitro CCK-A agonist activity on isolated guinea pig gallbladder.
- Observed in vivo induction of satiety in rats after drug administration.
Conclusions:
- The novel 1,4-benzodiazepine derivatives exhibit promising CCK-A agonist properties.
- These findings support the potential of this chemical class for developing new satiety-inducing agents.
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