Chiral pyrazoline amino acids (3aR,4S,6aR)-1a and (3aR,4S,6aR)-1b, and (3aS,6S,6aS)-2a and (3aS,6S,6aS)-2b, which are conformationally constrained analogues of glutamic and homoglutamic acid, respectively, were prepared via a strategy based on the 1,3-dipolar cycloaddition of a nitrile imine to methyl N-Boc-3,4-didehydro-(S)-prolinate. The new acids were tested for activity at ionotropic glutamate receptors. Solely the derivative (3aR,4S,6aR)-1a, which is structurally related to the previously described 4,5-dihydroisoxazole analogue (S)-CIP-A, turned out to be a potent and selective agonist for the AMPA receptors. The biological activity is due to the interaction with the orthosteric glutamate binding site.
|Titolo:||Synthesis of novel pyrrolo[3,4-d]pyrazole-dicarboxylic acids and evaluation of their interaction with glutamate receptors|
|Autori interni:||CONTI, PAOLA (Primo)|
JOPPOLO DI VENTIMIGLIA, SAMUELE (Secondo)
DE MICHELI, CARLO (Ultimo)
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||2008|
|Digital Object Identifier (DOI):||10.1002/cbdv.200890061|
|Appare nelle tipologie:||01 - Articolo su periodico|
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