title: Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists.
abstract: Continuing medicinal chemistry studies to identify spiropiperidine-derived NPY Y5 receptor antagonists are described. Aryl urea derivatives of a variety of spiropiperidines were tested for their NPY Y5 receptor binding affinities. Of the spiropiperidines so far examined, spiro[3-oxoisobenzofurane-1(3H),4'-piperidine] was a useful scaffold for producing orally active NPY Y5 receptor antagonists. Oral administration of 5c significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 3mg/kg. In addition, this compound was efficacious in decreasing body weight in diet-induced obese mice.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba 300-2611, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haga
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Nonoshita
authors.forename: Takunobu
authors.initials: T
authors.lastname: Shibata
authors.forename: Takuya
authors.initials: T
authors.lastname: Suga
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirohashi
authors.forename: Aya
authors.initials: A
authors.lastname: Sakuraba
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohe
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
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; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004435:Eating; D006801:Humans; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015431:Weight Loss
chemical_list: D019440:Anti-Obesity Agents; D010880:Piperidines; D017476:Receptors, Neuropeptide Y; D013141:Spiro Compounds; C100568:neuropeptide Y5 receptor; C542867:spiro(3-oxoisobenzofurane-1(3H),4'-piperidine); D014508:Urea