Syntheses and structure-activity relationships of novel, potent, and selective trans-2-[3-oxospiro[isobenzofuran-1(3H),1′-cyclohexan]-4′-yl]benzimidazole NPYY5 receptor antagonists

被引：19

作者：

Ogino, Yoshio ^{[1
]}

Ohtake, Norikazu ^{[1
]}

Nagae, Yoshikazu ^{[1
]}

Matsuda, Kenji ^{[1
]}

Ishikawa, Makoto ^{[1
]}

Moriya, Minoru ^{[1
]}

Kanesaka, Maki ^{[1
]}

Mitobe, Yuko ^{[1
]}

Ito, Junko ^{[1
]}

Kanno, Tetsuya ^{[1
]}

Ishihara, Akane ^{[1
]}

Iwaasa, Hisashi ^{[1
]}

Ohe, Tomoyuki ^{[1
]}

Kanatani, Akio ^{[1
]}

Fukami, Takehiro ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 18期

关键词：

neuropeptide Y; Y5; receptor; antagonist; anti-obesity; benzimidazole;

D O I：

10.1016/j.bmcl.2008.08.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Syntheses and structure-activity relationships of a novel class of 2-[3-oxospiro[isobenzofuran-1(3H), 1'-cyclohexan]-4'-yl]benzimidazole NPY Y5 receptor antagonists are described. Optimization of the lead compound 2a by incorporating substituents into the 5-position or into both the 5-and 6-positions of the benzimidazole core part led to the identification of 5-(5-methyl-1,2,4-oxadiazol-2-yl) benzimidazole (2r: IC(50) = 3.3 nM) and 5-(2-methyltetrazol-5-yl) benzimidazole (2u: IC(50) = 5.9 nM), both of which are potent, selective, and orally bioavailable Y5 receptor antagonists. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.

引用

页码：4997 / 5001

页数：5

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