In investigating potent sodium (Na ) channel blockers for the treatment of ischemic stroke, we synthesized a novel series of 3-amino-1-(5-indanyloxy)-2-propanol derivatives and evaluated their inhibitory effects on neuronal Na channels. The 3-amino-1-(5-indanyloxy)-2-propanol derivatives exhibited potent blocking activity for Na channels and a significantly low affinity for dopamine D 2 receptors, which demonstrates a minimal clinical risk for extrapyramidal side effects. In particular,

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... 4b, a 3-amino-1-(5-indanyloxy)-2-propanol derivative bearing a benzimidazole moiety, showed desirable neuroprotective activity in a rat transient middle cerebral artery occlusion model. Furthermore, compound 4b displayed a high binding affinity for neurotoxin receptor site 2 of the Na channels, which suggests that 4b would act as a use-dependent Na channel blocker in sustained depolarization during ischemic stroke.