Substituted N-(Biphenyl-4′-yl)methyl (R)-2-Acetamido-3-methoxypropionamides: Potent Anticonvulsants That Affect Frequency (Use) Dependence and Slow Inactivation of Sodium Channels

Title
Substituted N-(Biphenyl-4′-yl)methyl (R)-2-Acetamido-3-methoxypropionamides: Potent Anticonvulsants That Affect Frequency (Use) Dependence and Slow Inactivation of Sodium Channels
Authors
이효성박기덕Robert TorregrosaXiao-Fang YangErik T. DustrudeYuying WangSarah M. WilsonCindy BarbosaYucheng XiaoTheodore R. CumminsRajesh KhannaHarold Kohn
Issue Date
2014-07
Publisher
Journal of medicinal chemistry
Citation
VOL 57, 6165-6182
Abstract
We prepared 13 derivatives of N-(biphenyl-4′-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound’s whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI = TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.
URI
http://pubs.kist.re.kr/handle/201004/47911
ISSN
00222623
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KIST Publication > Article
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