discoveryofarylsulfonamideselectivenav17inhibitorswithahighlyhydrophobicethanoanthracenecore

doi:10.1038/s41401-019-0267-z

	discoveryofarylsulfonamideselectivenav17inhibitorswithahighlyhydrophobicethanoanthracenecore
	Wang Jintao; Zheng Yueming; Chen Yueting; Gu Min; Gao Zhaobing; Nan Fajun
刊名	actapharmacologicasinica
	2020
卷号	41 期号:3 页码:293
关键词	Nav1.7 sodium channel aryl sulfonamide maprotiline compound 10o electrophysiology acetic acid-induced visceral pain analgesic activity
ISSN号	1671-4083
DOI	10.1038/s41401-019-0267-z
英文摘要	Nav1.7 channels are mainly distributed in the peripheral nervous system. Blockade of Nav1.7 channels with small-molecule inhibitors in humans might provide pain relief without affecting the central nervous system. Based on the facts that many reported Nav1.7-selective inhibitors contain aryl sulfonamide fragments, as well as a tricyclic antidepressant, maprotiline, has been found to inhibit Nav1.7 channels, we designed and synthesized a series of compounds with ethanoanthracene and aryl sulfonamide moieties. Their inhibitory activity on sodium channels were detected with electrophysiological techniques. We found that compound 10o potently inhibited Nav1.7 channels stably expressed in HEK293 cells (IC50 = 0.64 ± 0.30 nmol/L) and displayed a high Nav1.7/Nav1.5 selectivity. In mouse small-sized dorsal root ganglion neurons, compound 10o (10, 100 nmol/L) dosedependently decreased the sodium currents and dramatically suppressed depolarizing current-elicited neuronal discharge. Preliminary in vivo experiments showed that compound 10o possessed good analgesic activity: in a mouse visceral pain model, administration of compound 10o (30–100 mg/kg, i.p.) effectively and dose-dependently suppressed acetic acid-induced writhing.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280709]
专题	中国科学院上海药物研究所
作者单位	中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Wang Jintao,Zheng Yueming,Chen Yueting,et al. discoveryofarylsulfonamideselectivenav17inhibitorswithahighlyhydrophobicethanoanthracenecore[J]. actapharmacologicasinica,2020,41(3):293.
APA	Wang Jintao,Zheng Yueming,Chen Yueting,Gu Min,Gao Zhaobing,&Nan Fajun.(2020).discoveryofarylsulfonamideselectivenav17inhibitorswithahighlyhydrophobicethanoanthracenecore.actapharmacologicasinica,41(3),293.
MLA	Wang Jintao,et al."discoveryofarylsulfonamideselectivenav17inhibitorswithahighlyhydrophobicethanoanthracenecore".actapharmacologicasinica 41.3(2020):293.