| Autor: |
Aquino, C. J., Armour, D. R., Berman, J. M., Birkemo, L. S., Carr, R. A. E., Croom, D. K., Dezube, M., Dougherty, R. W., Jr., Ervin, G. N., Grizzle, M. K., Head, J. E., Hirst, G. C., James, M. K., Johnson, M. F., Miller, L. J., Queen, K. L., Rimele, T. J., Smith, D. N., Sugg, E. E. |
| Zdroj: |
Journal of Medicinal Chemistry; January 19, 1996, Vol. 39 Issue: 2 p562-569, 8p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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