Discovery of 1,5-Benzodiazepines with Peripheral Cholecystokinin (CCK-A) Receptor Agonist Activity. 1. Optimization of the Agonist “Trigger”
Citations Over TimeTop 10% of 1996 papers
Abstract
Directed screening of compounds selected from the Glaxo registry file for contractile activity on the isolated guinea pig gallbladder (GPGB) identified a series of 1,5-benzodiazepines with peripheral cholecystokinin (CCK) receptor agonist activity. Agonist efficacy within this series was modulated by variation of substituents on the N1-anilinoacetamide moiety. Remarkably, a single methyl group confers agonist activity, with an N-isopropyl substituent providing optimal efficacy. Hydrophilic substituents on the anilino nitrogen abolish agonist activity or produce antagonists of CCK. In contrast, hydrophilic electron-donating groups at the para-position of the anilino ring enhance or maintain in vitro and in vivo agonist activity. Despite decreased affinity for the human CCK-A receptor, relative to CCK-8, some of these compounds are equipotent to CCK as anorectic agents in rats following intraperitoneal administration.
Related Papers
- → CCK-JMV-180: a peptide that distinguishes high-affinity cholecystokinin receptors from low-affinity cholecystokinin receptors(1989)79 cited
- → Characterization of Cholecystokinin Receptors and Messenger RNA Expression in Rat Pancreas: Evidence for Expression of Cholecystokinin-A Receptors but Not Cholecystokinin-B (Gastrin) Receptors(1995)24 cited
- → Pharmacological and biochemical characterization of cholecystokinin/gastrin receptors in developing rat pancreas(1992)20 cited
- → New proglumide-analogue CCK receptor antagonists: very potent and selective for peripheral tissues(1986)49 cited
- → SKF83959 is a partial agonist, not a functionally selective dopamine D 1 receptor ligand as commonly believed(2013)