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Design, synthesis and biological evaluation of novel tetrahydroisoquinoline quaternary derivatives as peripheral κ-opioid receptor agonists

被引：7
|
作者：
Guo, Ting [1 ]
Gan, Zongjie [1 ,2 ]
Chen, Jie [3 ]
Wang, Dechuan [1 ]
He, Ling [4 ]
Song, Qiao [1 ,2 ]
Xu, Yungen [1 ,2 ]
机构：
[1] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China
[2] China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Jiangsu, Peoples R China
[3] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
[4] China Pharmaceut Univ, Dept Pharmacol, Nanjing 210009, Jiangsu, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 13期
基金：
中国国家自然科学基金;
关键词：
Tetrahydroisoquinoline quaternary derivatives; Peripheral; kappa-Opioid receptor agonists; BLOOD-BRAIN-BARRIER; LIMITED ACCESS; AGENTS; SELECTIVITY; ICI-204448; DEPENDENCE;
D O I：
10.1016/j.bmc.2016.05.002
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A novel series of tetrahydroisoquinoline quaternary derivatives 4 were synthesized as peripheral kappa-opioid receptor agonists. All the target compounds were evaluated in kappa-opioid receptor binding assays, and compounds 4l, 4m, and 4n exhibited high affinity for kappa-opioid receptor. Furthermore, compound 4l (kappa K-i = 0.94 nM) produced potent antinociceptive activity in the mouse acetic acid-induced writhing assay, with lower sedative side effects than the parent compound MB-1c. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2964 / 2970
页数：7
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