Bioorganic and Medicinal Chemistry p. 2105 - 2114 (1996)
Update date:2022-07-29
Topics:
Choi, Daeock
Stables, James P.
Kohn, Harold
Recent studies have demonstrated that substituted N-benzyl 2-acetamidoacetamides provide significant protection against maximal electroshock (MES)-induced seizures in mice and rats. In this study, we investigated whether the 2-acetamido moiety was necessary for anticonvulsant activity. Ten derivatives of the known anticonvulsant, N-benzyl 2-acetamido-2-phenylacetamide were prepared in which the 2-acetamido group was replaced by hydrogen, methyl, oxygen, and halogen substituents. Evaluation of these compounds in the MES-induced seizure test demonstrated that both the hydroxy and the methoxy compounds provided full protection against MES-induced seizures in mice given ip at 100 mg/g. Moreover, evaluation of the individual stereoisomers for the hydroxy compound showed that the principal activity resided in the (R)-isomer. These findings demonstrated that the 2-acetamido substituent is important but not obligatory for the prevention of MES-induced seizures. Further supporting evidence was provided by comparing the pharmacological activities of N-benzyl 2,3-dimethoxypropionamide with N-benzyl 2-acetamido-3-methoxypropionamide. The ED50 value for the former in the MES test was 3.0 mg/kg (ip), which compared favorably with phenobarbital (ED50=22 mg/kg), but the ED50 value for N-benzyl 2-acetamido-3-methoxypropionamide was 8.3 mg/kg.
View MoreTianjin Dongchang Fine Chemical Industry Co., Ltd.
Contact:+86-22-29894595
Address:Economic Developing Zone, Ji County, Tianjin, China
Chemvon Biotechnology Co. Ltd.
website:http://www.chemvon.com
Contact:86-21-58550039;86-21-31268550-8004
Address:Suite B-10#, 6999 Chuansha Road, Pudong District, Shanghai 201202, China
Angelisun(Chongqing) Pharmaceutical Co., LTD.
Contact:+86-23-68030926-816
Address:D1-7 Tech & Entrepreneurs Park, Kecheng Road, Erlang Hi-Tech Areas, Chongqing, China
Zibo Xiaoguang Chemical Material Co., Ltd
Contact:15954099116
Address:Boshan Development Zone
Baicao Pharmaceutical Co., Ltd.
website:http://www.jxbaicao.com
Contact:+86-796-8113329
Address:It (country) economic and technological development zone of the jinggang mountains
Doi:10.1039/jr9530003635
(1953)Doi:10.1021/ja01141a080
(1952)Doi:10.1021/acs.jmedchem.1c00831
(2021)Doi:10.1246/cl.1988.1537
(1988)Doi:10.1021/jm800846u
(2009)Doi:10.1021/jm00326a030
(1965)