Author/Authors :
Graham S. Poindexter، نويسنده , , Marc A. Bruce، نويسنده , , Karen L. LeBoulluec، نويسنده , , Ivo Monkovic، نويسنده , , Scott W. Martin، نويسنده , , Eric M. Parker، نويسنده , , Larry G. Iben، نويسنده , , Rachel T. McGovern، نويسنده , , Astrid A. Ortiz، نويسنده , , Jennifer A. Stanley، نويسنده , , Gail K. Mattson، نويسنده , , Michael Kozlowski، نويسنده , , Meredith Arcuri، نويسنده , , Ildiko Antal-Zimanyi، نويسنده ,
Abstract :
Dihydropyridine 5a was found to be an inhibitor of neuropeptide Y1 binding in a high throughput 125I-PYY screening assay. Structure–activity studies around certain portions of the dihydropyridine chemotype identified BMS-193885 (6e) as a potent and selective Y1 receptor antagonist. In a forskolin-stimulated c-AMP production assay using CHO cells expressing the human Y1 receptor, 6e demonstrated full functional antagonism (Kb=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).
