Novel 3‐Carboxy‐ and 3‐Phosphonopyrazoline Amino Acids as Potent and Selective NMDA Receptor Antagonists: Design, Synthesis, and Pharmacological Characterization
2010; Wiley; Volume: 5; Issue: 9 Linguagem: Inglês
10.1002/cmdc.201000184
ISSN1860-7187
AutoresPaola Conti, Andrea Pinto, Lucia Tamborini, Ulf Madsen, Birgitte Nielsen, Hans Bräuner‐Osborne, Kasper B. Hansen, Elisa Landucci, Domenico E. Pellegrini‐Giampietro, Giovambattista De Sarro, Eugenio Donato Di Paola, Carlo De Micheli,
Tópico(s)Neuroscience and Neuropharmacology Research
ResumoAbstract The design and synthesis of new N1‐substituted 3‐carboxy‐ and 3‐phosphonopyrazoline and pyrazole amino acids that target the glutamate binding site of NMDA receptors are described. An analysis of the stereochemical requirements for high‐affinity interaction with these receptors was performed. We identified two highly potent and selective competitive NMDA receptor antagonists, (5 S ,α R )‐ 1 and (5 S ,α R )‐ 4 , which exhibit good in vitro neuroprotective activity and in vivo anticonvulsant activity by i.p. administration, suggesting that these molecules may have potential use as therapeutic agents.
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