Imidazol-1-ylethylindazole Voltage-Gated Sodium Channel Ligands Are Neuroprotective during Optic Neuritis in a Mouse Model of Multiple Sclerosis

被引：11

作者：

Browne, Lorcan ^{[1
]}

Lidster, Katie ^{[2
]}

Al-Izki, Sarah ^{[2
]}

Clutterbuck, Lisa ^{[1
]}

Posada, Cristina ^{[1
]}

Chan, A. W. Edith ^{[1
]}

Riddall, Dieter ^{[1
]}

Garthwaite, John ^{[1
]}

Baker, David ^{[2
]}

Selwood, David L. ^{[1
]}

机构：

[1] UCL, Wolfson Inst Biomed Sci, London WC1E 6BT, England

[2] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 07期

基金：

英国惠康基金;

关键词：

THERAPEUTIC TARGETS; CRYSTAL-STRUCTURE; NEUROPATHIC PAIN; ISCHEMIC DAMAGE; NERVOUS-SYSTEM; BRAIN-INJURY; LAMOTRIGINE; BLOCKERS; NEURONS; ENCEPHALOMYELITIS;

D O I：

10.1021/jm401881q

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of imidazol-1-ylethylindazole sodium channel ligands were developed and optimized for sodium channel inhibition and in vitro neuroprotective activity. The molecules exhibited displacement of a radiolabeled sodium channel ligand and selectivity for blockade of the inactivated state of cloned neuronal Na-v channels. Metabolically stable analogue 6 was able to protect retinal ganglion cells during optic neuritis in a mouse model of multiple sclerosis.

引用

页码：2942 / 2952

页数：11

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