Bioorganic & Medicinal Chemistry 2009-01-01

Design, synthesis and biological evaluation of novel bicyclo[1.1.1]pentane-based omega-acidic amino acids as glutamate receptors ligands.

Rosanna Filosa, M Carmela Fulco, Maura Marinozzi, Nicola Giacchè, Antonio Macchiarulo, Antonella Peduto, Antonio Massa, Paolo de Caprariis, Christian Thomsen, Claus T Christoffersen, Roberto Pellicciari

Index: Bioorg. Med. Chem. 17 , 242-50, (2009)

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Abstract

A novel series of bicyclo[1.1.1]pentane-based omega-acidic amino acids, including (2S)- and (2R)-3-(3'-carboxybicyclo[1.1.1]pentyl)alanines (8 and 9), (2S)- and (2R)-2-(3'-carboxymethylbicyclo[1.1.1]pentyl)glycines (10 and 11), and (2S)- and (2R)-3-(3'-phosphonomethylbicyclo[1.1.1]pentyl)glycines (12 and 13), were synthesized and evaluated as glutamate receptor ligands. Among them, (2R)-3-(3'-phosphonomethylbicyclo[1.1.1]pentyl)glycine (13) showed relatively high affinity and selectivity at the NMDA receptor. The results are also discussed in light of pharmacophoric modelling studies of NMDA agonists and antagonists.