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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Gaoni Y,Chapman AG,Parvez N,Pook PC,Jane DE,Watkins JCdoi
10.1021/jm00051a005subject
Has Abstractpub_date
1994-12-09 00:00:00pages
4288-96issue
25eissn
0022-2623issn
1520-4804journal_volume
37pub_type
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