Document Detail

Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.
MedLine Citation:
PMID:  12825948     Owner:  NLM     Status:  MEDLINE    
Bicyclic acidic amino acids (+/-)-6 and (+/-)-7, which are conformationally constrained homologues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested toward ionotropic and metabotropic glutamate receptor subtypes; both of them behaved as antagonists at mGluR1,5 and as agonists at mGluR2. Furthermore, whereas (+/-)-6 was inactive at all ionotropic glutamate receptors, (+/-)-7 displayed a quite potent antagonism at the NMDA receptors. In the in vivo tests on DBA/2 mice, the compounds displayed an anticonvulsant activity. The interesting pharmacological profile of (+/-)-7 qualifies it as a lead of novel neuroprotective agents.
Paola Conti; Marco De Amici; Samuele Joppolo Di Ventimiglia; Tine B Stensbøl; Ulf Madsen; Hans Bräuner-Osborne; Emilio Russo; Giovambattista De Sarro; Giuseppe Bruno; Carlo De Micheli
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  46     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-26     Completed Date:  2003-08-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3102-8     Citation Subset:  IM    
Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Milano, Viale Abruzzi 42, 20131 Milano, Italy.
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MeSH Terms
Amino Acids, Acidic / chemical synthesis*,  chemistry,  pharmacology
Amino Acids, Dicarboxylic / chemical synthesis*,  chemistry,  pharmacology
Anticonvulsants / chemical synthesis*,  chemistry,  pharmacology
CHO Cells
Cerebral Cortex / metabolism
Crystallography, X-Ray
Dicarboxylic Acids / chemical synthesis*,  chemistry,  pharmacology
Excitatory Amino Acid Agonists / chemical synthesis,  chemistry,  pharmacology
Excitatory Amino Acid Antagonists / chemical synthesis,  chemistry,  pharmacology
Heterocyclic Compounds, 2-Ring / chemical synthesis*,  chemistry,  pharmacology
Isoxazoles / chemical synthesis*,  chemistry,  pharmacology
Mice, Inbred DBA
Molecular Conformation
Receptors, Metabotropic Glutamate / agonists,  antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
Reg. No./Substance:
0/5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta(d)isoxazole-3,5-dicarboxylic acid; 0/Amino Acids, Acidic; 0/Amino Acids, Dicarboxylic; 0/Anticonvulsants; 0/Dicarboxylic Acids; 0/Excitatory Amino Acid Agonists; 0/Excitatory Amino Acid Antagonists; 0/Heterocyclic Compounds, 2-Ring; 0/Isoxazoles; 0/Receptors, Metabotropic Glutamate; 0/Receptors, N-Methyl-D-Aspartate; 0/metabotropic glutamate receptor 2; 0/metabotropic glutamate receptor 5; 0/metabotropic glutamate receptor type 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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