کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1363166 | 981504 | 2009 | 17 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Discovery of pyridone-containing imidazolines as potent and selective inhibitors of neuropeptide Y Y5 receptor Discovery of pyridone-containing imidazolines as potent and selective inhibitors of neuropeptide Y Y5 receptor](/preview/png/1363166.png)
A series of 2-pyridone-containing imidazoline derivatives was synthesized and evaluated as neuropeptide Y Y5 receptor antagonists. Optimization of the 2-pyridone structure on the 2-position of the imidazoline ring led to identification of 1-(difluoromethyl)-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin-3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]pyridin-2(1H)-one (7m). Compound 7m displayed statistically significant inhibition of food intake in an agonist-induced food intake model in SD rats and no adverse cardiovascular effects in anesthetized dogs. In addition, markedly higher brain penetrability and a lower plasma Occ90 value were observed in P-gp-deficient mdr1a (−/−) mice compared to mdr1a (+/+) mice after oral administration of 7m.
A series of imidazolines bearing 2-pyridone has been discovered as potent and selective neuropeptide Y Y5 receptor antagonists.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 16, 15 August 2009, Pages 6106–6122