Identification of novel and orally active spiroindoline NPY Y5 receptor antagonists

被引：17

作者：

Sakamoto, Toshihiro ^{[1
]}

Moriya, Minoru ^{[1
]}

Haga, Yuji ^{[1
]}

Takahashi, Toshiyuki ^{[1
]}

Shibata, Takunobu ^{[1
]}

Okamoto, Osamu ^{[1
]}

Nonoshita, Katsumasa ^{[1
]}

Kitazawa, Hidefumi ^{[1
]}

Hidaka, Masayasu ^{[1
]}

Gomori, Akira ^{[1
]}

Iwaasa, Hisashi ^{[1
]}

Ishihara, Akane ^{[1
]}

Kanatani, Akio ^{[1
]}

Fukami, Takehiro ^{[1
]}

Gao, Ying-Duo ^{[2
]}

MacNeil, Douglas J. ^{[2
]}

Yang, Lihu ^{[2
]}

机构：

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

[2] Merck Res Labs, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 06期

关键词：

NPY; Neuropeptide Y; Y5; receptor; Antagonist; Obesity; NEUROPEPTIDE YY5 RECEPTOR; PANCREATIC-POLYPEPTIDE; PEPTIDE-YY; POTENT ANTAGONISTS; Y1; RECEPTOR; FUNCTIONAL EXPRESSION; FEEDING-BEHAVIOR; FOOD-INTAKE; HYDRAZIDE DERIVATIVES; HIGH-AFFINITY;

D O I：

10.1016/j.bmcl.2009.02.035

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of spiroindoline-3,40-piperidine derivatives were synthesized and evaluated for their binding affinities and antagonistic activities at Y5 receptors. Potent Y5 antagonists were tested for their oral bioavailabilities and brain penetration in rats. Some of the antagonists showed good oral bioavailability and/ or good brain penetration. In particular, compound 6e was orally bioavailable and brain penetrant, and oral administration of 6e inhibited bPP-induced food intake in rats with a minimum effective dose of 10 mg/ kg. (C) 2009 Published by Elsevier Ltd.

引用

页码：1564 / 1568

页数：5

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