Synthesis and T-type calcium channel-blocking effects of aryl(1,5-disubstituted-pyrazol-3-yl)methyl sulfonamides for neuropathic pain treatment

被引：15
|
作者：
Kim, Jung Hyun [1 ]
Keum, Gyochang [1 ,2 ]
Chung, Hesson [1 ]
Nam, Ghilsoo [1 ,2 ]
机构：
[1] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul 136791, South Korea
[2] Korea Univ Sci & Technol UST, Dept Biol Chem, Gajungro 217, Daejeon 305350, South Korea
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 123卷
关键词：
T-type calcium channel inhibition; Aryl(1,5-disubstituted-pyrazol-3-yl)methyl sulfonamide; Neuropathic pain; Allodynia; CA2+ CHANNELS; PERIPHERAL NEUROPATHY; RAT; MODEL; ZONISAMIDE; ALLODYNIA; BLOCKERS; NEURONS;
D O I：
10.1016/j.ejmech.2016.07.032
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A novel series of aryl(1,5-disubstituted pyrazol-3-yl)methyl sulfonamide derivatives was designed, synthesized, and evaluated for T-type calcium channel (ctiG and chm) inhibitory activity. We identified several compounds, 9a, 9b, 9g, and 9h that displayed good T-type channel inhibitory potency with low hERG channel and CYP450 inhibition. Among them, 9a and 9b exhibited neuropathic pain alleviation effects in mechanical and cold allodynia induced in the SNL rat model. Compounds 9a and 9b displayed better efficacy than mibefradil and gabapentin against cold allodynia. In particular, compound 9a seemed to be valuable as shown fast acting performance in mechanical neuropathic pain model. (C) 2016 Elsevier Masson SAS. All rights reserved'.
引用
收藏
页码：665 / 672
页数：8
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