Dihydropyridine neuropeptide Y Y(1) receptor antagonists
| Autor: | Scott W. Martin, Rachel T. McGovern, Graham S. Poindexter, Meredith Arcuri, Ildiko Antal-Zimanyi, Eric M. Parker, Ivo Monkovic, Jennifer A. Stanley, Larry Iben, Marc Bruce, Karen Leboulluec, Astrid A. Ortiz, Michael R. Kozlowski, Gail K. Mattson |
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| Rok vydání: | 2002 |
| Předmět: |
Dihydropyridines
medicine.drug_class Clinical Biochemistry Pharmaceutical Science CHO Cells Pharmacology Biochemistry Cell Line Eating Radioligand Assay Structure-Activity Relationship Cricetinae Drug Discovery medicine Animals Humans Receptor Molecular Biology Chemistry Chinese hamster ovary cell Phenylurea Compounds Organic Chemistry Cell Membrane Dihydropyridine Antagonist Neuropeptide Y receptor Receptor antagonist In vitro Rats Receptors Neuropeptide Y Kinetics Molecular Medicine Anti-Obesity Agents medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry letters. 12(3) |
| ISSN: | 0960-894X |
| Popis: | Dihydropyridine 5a was found to be an inhibitor of neuropeptide Y(1) binding in a high throughput (125)I-PYY screening assay. Structure-activity studies around certain portions of the dihydropyridine chemotype identified BMS-193885 (6e) as a potent and selective Y(1) receptor antagonist. In a forskolin-stimulated c-AMP production assay using CHO cells expressing the human Y(1) receptor, 6e demonstrated full functional antagonism (K(b)=4.5 nM). Compound 6e inhibited NPY-induced feeding in satiated rats when dosed at 3.0 and 10.0 mg/kg (ip), and also decreased spontaneous overnight food consumption in rats at doses of 10 and 20 mg/kg (ip). |
| Databáze: | OpenAIRE |
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