SYNTHESIS, NMDA RECEPTOR ANTAGONIST ACTIVITY, AND ANTICONVULSANT ACTION OF 1-AMINOCYCLOBUTANECARBOXYLIC ACID-DERIVATIVES

被引:47
作者
GAONI, Y
CHAPMAN, AG
PARVEZ, N
POOK, PCK
JANE, DE
WATKINS, JC
机构
[1] INST PSYCHIAT,LONDON SE5 8AF,ENGLAND
[2] UNIV BRISTOL,SCH MED SCI,DEPT PHARMACOL,BRISTOL BS8 1TD,AVON,ENGLAND
关键词
D O I
10.1021/jm00051a005
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A range of cis- and trans-3-substituted 1-aminocyclobutane-1-carboxylic acids has been synthesized and evaluated for antagonism at excitatory amino acid receptor sites and for anticonvulsant activity. Potent and selective antagonist:activity at N-methyl-D-aspartate (NMDA) receptor sites in neonatal rat motoneurones was shown by compounds in which the 3-substituent was, or contained, a 2'-carboxyethyl or 2'-phosphonoethyl moiety. Substances 4b, 24, 35, and 40 were more potent than the standard NMDA receptor antagonist, D-2-amino-5-phosphonopentanoate (D-AP5) as NMDA antagonists in this preparation, and about equipotent with [3-(+/-)-2-carboxypiperazin-4-yl)-1-propyl]phosphonate (CPP). Anticonvulsant activity, as assessed following intracerebroventricular injection into audiogenic DBA/2 mice, generally paralleled NMDA receptor antagonist activity.
引用
收藏
页码:4288 / 4296
页数:9
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