Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists

被引：15

作者：

Takahashi, Toshiyuki ^{[1
]}

Haga, Yuji ^{[1
]}

Sakamoto, Toshihiro ^{[1
]}

Moriya, Minoru ^{[1
]}

Okamoto, Osamu ^{[1
]}

Nonoshita, Katsumasa ^{[1
]}

Shibata, Takunobu ^{[1
]}

Suga, Takuya ^{[1
]}

Takahashi, Hirobumi ^{[1
]}

Hirohashi, Tomoko ^{[1
]}

Sakuraba, Aya ^{[1
]}

Gomori, Akira ^{[1
]}

Iwaasa, Hisashi ^{[1
]}

Ohe, Tomoyuki ^{[1
]}

Ishihara, Akane ^{[1
]}

Ishii, Yasuyuki ^{[1
]}

Kanatani, Akio ^{[1
]}

Fukami, Takehiro ^{[1
]}

机构：

[1] Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 13期

关键词：

Neuropeptide Y; NPY; Antagonist; Obesity; GROWTH-HORMONE SECRETAGOGUE; PEPTIDE-YY RECEPTOR; NEUROPEPTIDE-Y; PANCREATIC-POLYPEPTIDE; FUNCTIONAL EXPRESSION; FEEDING-BEHAVIOR; HIGH-AFFINITY; FOOD-INTAKE; BIOLOGICAL-ACTIVITIES; OBESE MICE;

D O I：

10.1016/j.bmcl.2009.05.013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 3 mg/kg. In addition, this compound was efficacious in decreasing body weight in diet-induced obese mice. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3511 / 3516

页数：6

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