Novel 3-carboxy- and 3-phosphonopyrazoline amino acids as potent and selective NMDA receptor antagonists: Design, synthesis, and pharmacological characterization

Paola Conti; Andrea Pinto; Lucia Tamborini; Ulf Madsen; Birgitte Nielsen; Hans Bräuner-Osborne; Kasper Bø Hansen; Elisa Landucci; Domenico E Pellegrini-Giampietro; Giovambattista De Sarro; Eugenio Donato Di Paola; Carlo De Micheli

doi:10.1002/cmdc.201000184

Novel 3-carboxy- and 3-phosphonopyrazoline amino acids as potent and selective NMDA receptor antagonists: Design, synthesis, and pharmacological characterization

Paola Conti, Andrea Pinto, Lucia Tamborini, Ulf Madsen, Birgitte Nielsen, Hans Bräuner-Osborne, Kasper Bø Hansen, Elisa Landucci, Domenico E Pellegrini-Giampietro, Giovambattista De Sarro, Eugenio Donato Di Paola, Carlo De Micheli

18 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	ChemMedChem
Vol/bind	5
Udgave nummer	9
Sider (fra-til)	1465-1475
ISSN	1860-7179
DOI	https://doi.org/10.1002/cmdc.201000184
Status	Udgivet - 3 sep. 2010

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Conti, P., Pinto, A., Tamborini, L., Madsen, U., Nielsen, B., Bräuner-Osborne, H., Hansen, K. B., Landucci, E., Pellegrini-Giampietro, D. E., De Sarro, G., Donato Di Paola, E., & De Micheli, C. (2010). Novel 3-carboxy- and 3-phosphonopyrazoline amino acids as potent and selective NMDA receptor antagonists: Design, synthesis, and pharmacological characterization. ChemMedChem, 5(9), 1465-1475. https://doi.org/10.1002/cmdc.201000184

Conti, P, Pinto, A, Tamborini, L, Madsen, U , Nielsen, B , Bräuner-Osborne, H, Hansen, KB, Landucci, E, Pellegrini-Giampietro, DE, De Sarro, G, Donato Di Paola, E & De Micheli, C 2010, 'Novel 3-carboxy- and 3-phosphonopyrazoline amino acids as potent and selective NMDA receptor antagonists: Design, synthesis, and pharmacological characterization', ChemMedChem, bind 5, nr. 9, s. 1465-1475. https://doi.org/10.1002/cmdc.201000184

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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 Bø

AU - Landucci, Elisa

AU - Pellegrini-Giampietro, Domenico E

AU - De Sarro, Giovambattista

AU - Donato Di Paola, Eugenio

AU - De Micheli, Carlo

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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 - Former Faculty of Pharmaceutical Sciences

U2 - 10.1002/cmdc.201000184

DO - 10.1002/cmdc.201000184

M3 - Journal article

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JO - Farmaco, Edizione Pratica

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ER -

Novel 3-carboxy- and 3-phosphonopyrazoline amino acids as potent and selective NMDA receptor antagonists: Design, synthesis, and pharmacological characterization

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