| Literature DB >> 8558528 |
C J Aquino1, D R Armour, J M Berman, L S Birkemo, R A Carr, D K Croom, M Dezube, R W Dougherty, G N Ervin, M K Grizzle, J E Head, G C Hirst, M K James, M F Johnson, L J Miller, K L Queen, T J Rimele, D N Smith, E E Sugg.
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.Entities:
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Year: 1996 PMID： 8558528 DOI： 10.1021/jm950626d
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446