Design, synthesis, and biological activities of 1-aryl-1,4-diazepan-2-one derivatives as novel triple reuptake inhibitors

被引：6

作者：

Honda, Eiji ^{[1
]}

Ishichi, Yuji ^{[1
]}

Kimura, Eiji ^{[1
]}

Yoshikawa, Masato ^{[1
]}

Kanzaki, Naoyuki ^{[1
]}

Nakagawa, Hideyuki ^{[1
]}

Terao, Yasuko ^{[1
]}

Suzuki, Atsuko ^{[1
]}

Kawai, Takayuki ^{[1
]}

Arakawa, Yuuichi ^{[1
]}

Ohta, Hiroyuki ^{[1
]}

Terauchi, Jun ^{[1
]}

机构：

[1] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Fujisawa, Kanagawa 2518555, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 16期

关键词：

Monoamine reuptake inhibition; Triple reuptake inhibition; 1-Aryl-1,4-diazepan-2-one compounds; Tail suspension test; Antidepressant; MAJOR DEPRESSIVE DISORDER; ANTIDEPRESSANTS; TOLERABILITY; AMITIFADINE; EFFICACY;

D O I：

10.1016/j.bmcl.2014.06.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of triple reuptake inhibitors were explored by ligand-based drug design. A cyclic structure was designed from cyclopropane derivative 5 using the core structure of reported monoamine reuptake inhibitors, leading to the formation of the 1-aryl-1,4-diazepan-2-one derivative 23j-S. Compound 23j-S was shown to act as a potent TRI with an excellent ADME-Tox profile. Oral administration of 23j-S significantly enhanced norepinephrine, dopamine, and serotonin levels in the mouse prefrontal cortex and showed significant antidepressant-like activity in tail suspension tests in mouse. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：3898 / 3902

页数：5

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