Design and Synthesis of the Potent, Orally Available, Brain-Penetrable Arylpyrazole Class of Neuropeptide Y5 Receptor Antagonists
| Autor: | Takunobu Shibata, Naoko Fujino, Akane Ishihara, Hidefumi Kitazawa, Yuko Koike, Aya Sakuraba, Takehiro Fukami, Katsumasa Nonoshita, Yuji Haga, Miki Sato, Toshiyuki Takahashi, Masaaki Hirose, Nagaaki Sato, Yasuyuki Ishii, and Akio Kanatani |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Agonist
medicine.drug_class Administration Oral Neuropeptide Naphthalenes Pharmacology Pancreatic Polypeptide Chemical synthesis Permeability Rats Sprague-Dawley Eating Structure-Activity Relationship Oral administration In vivo Drug Discovery medicine Animals Humans Pancreatic polypeptide Injections Intraventricular Chemistry Antagonist Brain Stereoisomerism Neuropeptide Y receptor Rats Receptors Neuropeptide Y Biochemistry Pyrazoles Molecular Medicine Cattle |
| Zdroj: | Journal of Medicinal Chemistry. 46:666-669 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm025513q |
| Popis: | Novel arylpyrazole derivatives were synthesized and evaluated as neuropeptide Y (NPY) Y5 receptor antagonists. Compound (-)-7, which features a novel chiral 2,3-dihydro-1H-cyclopenta[a]naphthalene moiety, showed good binding affinity and antagonistic activity for the Y5 receptor. After intracerebroventricular administration in SD rats, (-)-7 significantly inhibited food intake that was induced by the centrally administered Y5-preferring agonist, bovine pancreatic polypeptide, but had only a negligible effect on NPY-induced feeding. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|