Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists.
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.
Takahashi
Toshiyuki
T
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba 300-2611, Japan.
Haga
Yuji
Y
Sakamoto
Toshihiro
T
Moriya
Minoru
M
Okamoto
Osamu
O
Nonoshita
Katsumasa
K
Shibata
Takunobu
T
Suga
Takuya
T
Takahashi
Hirobumi
H
Hirohashi
Tomoko
T
Sakuraba
Aya
A
Gomori
Akira
A
Iwaasa
Hisashi
H
Ohe
Tomoyuki
T
Ishihara
Akane
A
Ishii
Yasuyuki
Y
Kanatani
Akio
A
Fukami
Takehiro
T
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
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