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

共 50 条

[31] Design, Synthesis, and Biological Evaluation of Novel PDE-4 Inhibitors [J].

Gao, Sufan ;

Xu, Qinlong ;

Li, Jiaming ;

Chu, Zhaoxing ;

He, Guangwei ;

Lin, Gaofeng ;

Zhu, Zhenwei ;

Cui, Yong ;

Mo, Jiajia ;

Guo, Jing ;

Zhao, Yan .

CHINESE JOURNAL OF ORGANIC CHEMISTRY, 2018, 38 (02) :478-485

[32] Treating brain tumors with PDE4 inhibitors [J].

Sengupta, Rajarshi ;

Sun, Tao ;

Warrington, Nicole M. ;

Rubin, Joshua B. .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2011, 32 (06) :337-344

[33] Design and synthesis of 4-alkynyl pyrazoles as inhibitors of PDE4: A practical access via Pd/C-Cu catalysis [J].

Gorja, Dhilli Rao ;

Kumar, K. Shiva ;

Kandale, Ajit ;

Meda, Chandana Lakshmi T. ;

Parsa, Kishore V. L. ;

Mukkanti, K. ;

Pal, Manojit .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (07) :2480-2487

[34] Antidepressant-like effects of PDE4 inhibitors mediated by the high-affinity rolipram binding state (HARBS) of the phosphodiesterase-4 enzyme (PDE4) in rats [J].

Zhang, HT ;

Zhao, Y ;

Huang, Y ;

Deng, CJ ;

Hopper, AT ;

De Vivo, M ;

Rose, GM ;

O'Donnell, JM .

PSYCHOPHARMACOLOGY, 2006, 186 (02) :209-217

[35] Discovery of oral and inhaled PDE4 inhibitors [J].

Ting, Pauline C. ;

Lee, Joe F. ;

Kuang, Rongze ;

Cao, Jianhua ;

Gu, Danlin ;

Huang, Ying ;

Liu, Zhidan ;

Aslanian, Robert G. ;

Feng, Kung-I. ;

Prelusky, Daniel ;

Lamca, James ;

House, Aileen ;

Phillips, Jonathan E. ;

Wang, Peng ;

Wu, Ping ;

Lundell, Daniel ;

Chapman, Richard W. ;

Celly, Chander S. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (20) :5528-5532

[36] Synthesis, biological evaluation and molecular modelling studies on benzothiadiazine derivatives as PDE4 selective inhibitors [J].

Tait, A ;

Luppi, A ;

Hatzelmann, A ;

Fossa, P ;

Mosti, L .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (04) :1393-1402

[37] Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors [J].

Goto, Taiji ;

Shiina, Akiko ;

Yoshino, Toshiharu ;

Mizukami, Kiyoshi ;

Hirahara, Kazuki ;

Suzuki, Osamu ;

Sogawa, Yoshitaka ;

Takahashi, Tomoko ;

Mikkaichi, Tsuyoshi ;

Nakao, Naoki ;

Takahashi, Mizuki ;

Hasegawa, Masashi ;

Sasaki, Shigeki .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (11) :3325-3328

[38] A comparison of the inhibitory activity of PDE4 inhibitors on leukocyte PDE4 activity in vitro and eosinophil trafficking in vivo [J].

Cooper, N ;

Teixeira, MM ;

Warneck, J ;

Miotla, JM ;

Wills, RE ;

Macari, DMT ;

Gristwood, RW ;

Hellewell, PG .

BRITISH JOURNAL OF PHARMACOLOGY, 1999, 126 (08) :1863-1871

[39] Montmorillonite K-10 mediated green synthesis of cyano pyridines: Their evaluation as potential inhibitors of PDE4 [J].

Reddy, T. Ram ;

Reddy, G. Rajeshwar ;

Reddy, L. Srinivasula ;

Jammula, Subbarao ;

Lingappa, Y. ;

Kapavarapu, Ravikumar ;

Meda, Chandana Lakshmi T. ;

Parsa, Kishore V. L. ;

Pal, Manojit .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 48 :265-274

[40] Targeting next-generation PDE4 inhibitors in search of potential management of rheumatoid arthritis and psoriasis [J].

Bhuktar, Harshavardhan ;

Thirupataiah, B. ;

Mounika, Guntipally ;

Samarpita, Snigdha ;

Rithvik, Arulkumaran ;

Priya, S. V. S. Sasi ;

Naskar, Roumi ;

Medishetti, Raghavender ;

Jagadish, P. C. ;

Parsa, Kishore V. L. ;

Rasool, Mahaboobkhan ;

Chakraborty, Sandipan ;

Pal, Manojit .

BIOORGANIC CHEMISTRY, 2024, 151

← 1 2 3 4 5 →