Discovery and biological profile of 4-(1-aryltriazol-4-yl)-tetrahydropyridines as an orally active new class of metabotropic glutamate receptor 1 antagonist

被引：58

作者：

Ito, Satoru ^{[1
]}

Satoh, Atsushi ^{[1
]}

Nagatomi, Yasushi ^{[1
]}

Hirata, Yukari ^{[1
]}

Suzuki, Gentaroh ^{[1
]}

Kimura, Toshifumi ^{[1
]}

Satow, Akio ^{[1
]}

Maehara, Shunsuke ^{[1
]}

Hikichi, Hirohiko ^{[1
]}

Hata, Mikiko ^{[1
]}

Kawamoto, Hiroshi ^{[1
]}

Ohta, Hisashi ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 22期

关键词：

mGluRs; Antagonist; Oral antagonistic activity;

D O I：

10.1016/j.bmc.2008.09.060

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We describe here the discovery and the structure-activity relationship (SAR) of a series of 4-(1-Aryl-triazol-4- yl)-tetrahydropyridines as novel mGluR1 antagonists. Our extensive chemical modi. cation of lead compound 2 successfully led to fluoropyridine analogs 7j and 1 with improved in vivo antagonistic activities. Among the evaluated compounds, chemically stable urea analog 1 showed oral antagonistic activity at dose ranges of 10-30 mg/kg in an animal model. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：9817 / 9829

页数：13

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