| Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids. | |
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MedLine Citation:
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PMID: 12825948 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 46 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2003 Jul |
Date Detail:
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Created Date: 2003-06-26 Completed Date: 2003-08-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 3102-8 Citation Subset: IM |
Affiliation:
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Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Milano, Viale Abruzzi 42, 20131 Milano, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids, Acidic
/
chemical synthesis*,
chemistry,
pharmacology Amino Acids, Dicarboxylic / chemical synthesis*, chemistry, pharmacology Animals Anticonvulsants / chemical synthesis*, chemistry, pharmacology CHO Cells Cerebral Cortex / metabolism Cricetinae 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 Male Mice Mice, Inbred DBA Molecular Conformation Rats Receptors, Metabotropic Glutamate / agonists, antagonists & inhibitors Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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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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