Lee, Hyosung Park, Ki Duk Torregrosa, Robert Yang, Xiao-Fang Dustrude, Erik T. Wang, Yuying Wilson, Sarah M. Barbosa, Cindy Xiao, Yucheng Cummins, Theodore R. Khanna, Rajesh Kohn, Harold 2024-01-20T09:30:48Z 2024-01-20T09:30:48Z 2021-08-31 2014-07-24 0022-2623 https://pubs.kist.re.kr/handle/201004/126579 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. English AMER CHEMICAL SOC ION CHANNELS ANTIEPILEPTIC DRUGS LACOSAMIDE EXPRESSION LIDOCAINE DISCOVERY EPILEPSY CURRENTS TARGETS MODELS Substituted N-(Biphenyl-4 '-yl)methyl (R)-2-Acetamido-3-methoxypropionamides: Potent Anticonvulsants That Affect Frequency (Use) Dependence and Slow Inactivation of Sodium Channels Article 10.1021/jm500707r 1 JOURNAL OF MEDICINAL CHEMISTRY, v.57, no.14, pp.6165 - 6182 JOURNAL OF MEDICINAL CHEMISTRY 57 14 6165 6182 scie scopus 000339540800026 Chemistry, Medicinal Pharmacology & Pharmacy Article ION CHANNELS ANTIEPILEPTIC DRUGS LACOSAMIDE EXPRESSION LIDOCAINE DISCOVERY EPILEPSY CURRENTS TARGETS MODELS