Discovery and biological profile of isoindolinone derivatives as novel metabotropic glutamate receptor 1 antagonists: A potential treatment for psychotic disorders

被引：56

作者：

Ito, Satoru ^{[1
]}

Hirata, Yukari ^{[1
]}

Nagatomi, Yasushi ^{[1
]}

Satoh, Atsushi ^{[1
]}

Suzuki, Gentaroh ^{[1
]}

Kimura, Toshifumi ^{[1
]}

Satow, Akio ^{[1
]}

Maehara, Shunsuke ^{[1
]}

Hikichi, Hirohiko ^{[1
]}

Hata, Mikiko ^{[1
]}

Ohta, Hisashi ^{[1
]}

Kawamoto, Hiroshi ^{[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 / 18期

关键词：

mGluR1; Antagonist; Glutamate; Psychotic disorder; GLUTAMATE-RECEPTOR-1; ANTAGONIST; METABOLIC-ACTIVATION; FTIDC;

D O I：

10.1016/j.bmcl.2009.07.145

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe here the discovery and biological profile of a series of isoindolinone derivatives as developed mGluR1 antagonists. Our combined strategy of rapid parallel synthesis and conventional medicinal optimization successfully led to N-cyclopropyl 22 and N-isopropyl isoindolinone analogs 21 and 23 with improved in vivo DMPK profiles. Moreover the most advanced analog 23 showed an oral antipsychotic-like effect at a dose of 1 mg/kg in an animal model. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5310 / 5313

页数：4

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