TY - JOUR
T1 - Novel 3-carboxy-and 3-phosphonopyrazoline amino acids as potent and selective NMDA receptor antagonists
T2 - Design, synthesis, and pharmacological characterization
AU - Conti, Paola
AU - Pinto, Andrea
AU - Tamborini, Lucia
AU - Madsen, Ulf
AU - Nielsen, Birgitte
AU - Bräuner-Osborne, Hans
AU - Hansen, Kasper B.
AU - Landucci, Elisa
AU - Pellegrini-Giampietro, Domenico E.
AU - De Sarro, Giovambattista
AU - Paola, Eugenio Donato Di
AU - De Micheli, Carlo
PY - 2010/9/3
Y1 - 2010/9/3
N2 - The design and synthesis of new N1-substituted 3-carboxyand 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, (5S,αR)-1 and (5S,αR)-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.
AB - The design and synthesis of new N1-substituted 3-carboxyand 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, (5S,αR)-1 and (5S,αR)-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.
KW - 1,3-dipolar cycloaddition
KW - Anticonvulsant activity
KW - NMDA receptor antagonists
KW - Neuroprotection
KW - Pyrazolines
UR - http://www.scopus.com/inward/record.url?scp=77956396684&partnerID=8YFLogxK
U2 - 10.1002/cmdc.201000184
DO - 10.1002/cmdc.201000184
M3 - Article
C2 - 20665761
AN - SCOPUS:77956396684
SN - 1860-7179
VL - 5
SP - 1465
EP - 1475
JO - ChemMedChem
JF - ChemMedChem
IS - 9
ER -