Synthesis, NMDA Receptor Antagonist Activity, and Anticonvulsant Action of 1-Aminocyclobutanecarboxylic Acid Derivatives
- 1 December 1994
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 37 (25) , 4288-4296
- https://doi.org/10.1021/jm00051a005
Abstract
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.Keywords
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