title: Synthesis of novel N1-substituted bicyclic pyrazole amino acids and evaluation of their interaction with glutamate receptors.
abstract: N1-substituted bicyclic pyrazole amino acids (S)-9a-9c and (R)-9a-9c, which are conformationally constrained analogues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested for activity at ionotropic and metabotropic glutamate receptors. Some of them turned out to be selective for the NMDA receptors, where they behaved as weak antagonists. The biological activity is mainly due to the interaction with the glutamate binding site, and not with the glycine co-agonist site.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Milano, Viale Abruzzi 42, I-20131 Milano. paola.conti@unimi.it
authors.forename: Paola
authors.initials: P
authors.lastname: Conti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grazioso
authors.forename: Samuele Joppolo
authors.initials: SJ
authors.lastname: di Ventimiglia
authors.forename: Andrea
authors.initials: A
authors.lastname: Pinto
authors.forename: Gabriella
authors.initials: G
authors.lastname: Roda
authors.forename: Ulf
authors.initials: U
authors.lastname: Madsen
authors.forename: Hans
authors.initials: H
authors.lastname: Bräuner-Osborne
authors.forename: Birgitte
authors.initials: B
authors.lastname: Nielsen
authors.forename: Chiara
authors.initials: C
authors.lastname: Costagli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Galli
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000138:chemical synthesis / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis / Q000378:metabolism; D015394:Molecular Structure; D017470:Receptors, Glutamate / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate