Design and synthesis of novel PDE4 inhibitors as potential candidates for antidepressant agents

被引：1

作者：

Yu, Yingcong ^{[1
]}

Zhao, Yan ^{[2
,3
]}

Wang, Yajing ^{[2
,3
]}

Huang, Xianfeng ^{[2
,3
,4
,5
]}

机构：

[1] Wenzhou Med Univ, Wenzhou Peoples Hosp, Clin Inst, Wenzhou, Peoples R China

[2] Changzhou Univ, Sch Pharm, Changzhou, Peoples R China

[3] Changzhou Univ, Sch Med, Changzhou, Peoples R China

[4] Changzhou Univ, Sch Pharm, Changzhou 213164, Jiangsu, Peoples R China

[5] Changzhou Univ, Sch Med, Changzhou 213164, Jiangsu, Peoples R China

来源：

JOURNAL OF CHEMICAL RESEARCH | 2023年 / 47卷 / 05期

基金：

中国国家自然科学基金;

关键词：

behavior tests; cAMP; depression; diarylpyrazoles; PDE4; inhibitors; MAJOR DEPRESSIVE DISORDER; RESVERATROL; MEMORY;

D O I：

10.1177/17475198231202967

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

PDE4 inhibitors exhibit anti-stress and antidepressant-like abilities by catalyzing the hydrolysis of cAMP, a primary regulator for intracellular communication in the brain. Herein, novel diarylpyrazole derivatives are synthesized and investigated for their ability to inhibit PDE4. In vitro studies indicate that most of the synthesized compounds show significant potency for the inhibition of PDE4. Specifically, N-(4-(3-(3,5-dimethoxyphenyl)-1H-pyrazol-5-yl)benzyl)-2-morpholinoethan-1-amine exhibits the most potent PDE4 inhibition, with an IC50 value of ca. 0.09 mu M. It also produces antidepressant-like activities in sugar water consumption and in forced swimming tests in vivo.

引用

页数：10

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