Identification of N-substituted 8-azatetrahydroquinolone derivatives as selective and orally active M1 and M4 muscarinic acetylcholine receptors agonists

被引：9

作者：

Takai, Kentaro ^{[1
]}

Inoue, Yasunao ^{[1
]}

Konishi, Yasuko ^{[1
]}

Suwa, Atsushi ^{[1
]}

Uruno, Yoshiharu ^{[1
]}

Matsuda, Harumi ^{[1
]}

Nakako, Tomokazu ^{[1
]}

Sakai, Mutsuko ^{[1
]}

Nishikawa, Hiroyuki ^{[1
]}

Hashimoto, Gakuji ^{[1
]}

Enomoto, Takeshi ^{[1
]}

Kitamura, Atsushi ^{[1
]}

Uematsu, Yasuaki ^{[1
]}

Kiyoshi, Akihiko ^{[1
]}

Sumiyoshi, Takaaki ^{[1
]}

机构：

[1] Dainippon Sumitomo Pharma Co Ltd, Drug Res Div, Suita, Osaka, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 16期

关键词：

M-1 muscarinic acetylcholine receptor; M-4 muscarinic acetylcholine receptor; Selective agonist; Schizophrenia; Antipsychotic agents; 8-Azatetrahydroquinolone; XANOMELINE; SCHIZOPHRENIA; PHARMACOLOGY; SYMPTOMS; MICE;

D O I：

10.1016/j.bmcl.2013.06.013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We designed and synthesized N-substituted 8-azatetrahydroquinolone derivatives as selective M-1 and M-4 muscarinic acetylcholine receptors agonists. Optimization of selected derivatives led to the discovery of compound 7 as a highly potent M-1 and M-4 agonist with weak hERG inhibition. Oral administration of compound 7 improved psychosis-like behavior in rats. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4644 / 4647

页数：4

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