Referenced in: none

Automatically associated channels: Kir2.3

Title: Synthesis of novel pyrrolo[3,4-d]pyrazole-dicarboxylic acids and evaluation of their interaction with glutamate receptors.

Authors: Paola Conti, Samuele Joppolo di Ventimiglia, Andrea Pinto, Lucia Tamborini, Frank S Menniti, John T Lazzaro, Carlo De Micheli

Journal, date & volume: Chem. Biodivers., 2008 Apr , 5, 657-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18421758

Abstract
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 'amino 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.