title: Design and synthesis of the potent, orally available, brain-penetrable arylpyrazole class of neuropeptide Y5 receptor antagonists.
abstract: 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.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba 300-2611, Japan. satoung@banyu.co.jp
authors.forename: Nagaaki
authors.initials: N
authors.lastname: Sato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takunobu
authors.initials: T
authors.lastname: Shibata
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haga
authors.forename: Aya
authors.initials: A
authors.lastname: Sakuraba
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hirose
authors.forename: Miki
authors.initials: M
authors.lastname: Sato
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Nonoshita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Koike
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kitazawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Fujino
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D004435:Eating / Q000187:drug effects; D006801:Humans; D007276:Injections, Intraventricular; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D010539:Permeability; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D009281:Naphthalenes; D011720:Pyrazoles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; D010191:Pancreatic Polypeptide