NOVEL 1-PHENYLCYCLOALKANECARBOXYLIC ACID-DERIVATIVES AS POTENTIAL ANTICONVULSANT AGENTS

被引:12
作者
CALDERON, SN
NEWMAN, AH
TORTELLA, FC
机构
[1] WALTER REED ARMY MED CTR,DEPT APPL BIOCHEM,WASHINGTON,DC 20307
[2] WALTER REED ARMY MED CTR,NEUROPHARMACOL BRANCH,WASHINGTON,DC 20307
关键词
D O I
10.1021/jm00115a002
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of analogues based on the anticonvulsant carbetapentane (1, 2-[2-(diethylamino)ethoxy]ethyl 1-phenyl-1-cyclopentylcarboxylate) was prepared as potential novel anticonvulsant drugs. Structure-activity relationships of analogues in which the ester function and cyclopentane moieties were modified have been investigated by evaluating their ability to prevent seizures in the rat maximal electroshock test. These compounds (11, ED50 = 16-mu-mol/kg; 12, ED50 = 86-mu-mol/kg, and 23, ED50 = 173-mu-mol/kg) were effective anticonvulsants. Compound 11, an alkyl ether derivative of 1, was more potent than the parent compound (ED50 = 48-mu-mol/kg) and also showed a 2-fold increase in potency compared to that of the prototypic anticonvulsant drug diphenylhydantoin.
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页码:3159 / 3164
页数:6
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