Discovery of isoxazole voltage gated sodium channel blockers for treatment of chronic pain.

Pengcheng P Shao,Feng Ye,Ann E Weber,Xiaohua Li,Kathryn A Lyons,William H Parsons,Maria L Garcia,Birgit T Priest,McHardy M Smith,John P Felix,Brande S Williams,Gregory J Kaczorowski,Erin McGowan,Catherine Abbadie,William J Martin,Daniel R McMasters,Ying-Duo Gao

Bioorganic & Medicinal Chemistry Letters（2009）

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摘要

A series of novel isoxazole voltage gated sodium channel blockers have been synthesized and evaluated. Substitutions on the benzylic position of benzamide were investigated to determine their effect on Nav1.7 inhibitory potency. The spirocyclobutyl substitution had the most significant enhancement on Nav1.7 inhibitory activity.

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关键词

Voltage gated sodium channel blocker,Neuropathic pain,Inflammatory pain,Amide replacement,Heterocycles,Isoxazole

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