4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues

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Standard

4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues. / Lolli, Marco L; Giordano, Cecilia; Pickering, Darryl S; Rolando, Barbara; Hansen, Kasper B; Foti, Antonio; Contreras-Sanz, Alberto; Amir, Ahmad; Fruttero, Roberta; Gasco, Alberto; Nielsen, Birgitte; Johansen, Tommy N.

In: Journal of Medicinal Chemistry, Vol. 53, No. 10, 2010, p. 4110-8.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Lolli, ML, Giordano, C, Pickering, DS, Rolando, B, Hansen, KB, Foti, A, Contreras-Sanz, A, Amir, A, Fruttero, R, Gasco, A, Nielsen, B & Johansen, TN 2010, '4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues', Journal of Medicinal Chemistry, vol. 53, no. 10, pp. 4110-8. https://doi.org/10.1021/jm1001452

APA

Lolli, M. L., Giordano, C., Pickering, D. S., Rolando, B., Hansen, K. B., Foti, A., Contreras-Sanz, A., Amir, A., Fruttero, R., Gasco, A., Nielsen, B., & Johansen, T. N. (2010). 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues. Journal of Medicinal Chemistry, 53(10), 4110-8. https://doi.org/10.1021/jm1001452

Vancouver

Lolli ML, Giordano C, Pickering DS, Rolando B, Hansen KB, Foti A et al. 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues. Journal of Medicinal Chemistry. 2010;53(10):4110-8. https://doi.org/10.1021/jm1001452

Author

Lolli, Marco L ; Giordano, Cecilia ; Pickering, Darryl S ; Rolando, Barbara ; Hansen, Kasper B ; Foti, Antonio ; Contreras-Sanz, Alberto ; Amir, Ahmad ; Fruttero, Roberta ; Gasco, Alberto ; Nielsen, Birgitte ; Johansen, Tommy N. / 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 10. pp. 4110-8.

Bibtex

@article{b7737c406e8c11df928f000ea68e967b,
title = "4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues",
abstract = "In order to investigate the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as a carboxylic acid bioisoster at ionotropic glutamate receptors (iGluRs), a series of acidic alpha-aminocarboxylic acids in which the distal carboxy group was replaced by the 4-hydroxy-1,2,5-oxadiazol-3-yl group was synthesized. Ionization constants were determined. All target compounds, except the Asp analogue 12, were resolved using chiral HPLC. Whereas 12 showed good affinity exclusively at NMDA receptors, the Glu analogue, (+)-10, was an unselective, though potent AMPA receptor preferring agonist (EC(50) = 10 microM at iGluR2) showing only low stereoselectivity. The two higher Glu homologues, (+)-15 and (+)-18, turned out to be weak agonists at iGluR2 as well as weak antagonists at NR1/NR2A, whereas the corresponding (-)-isomers were selective NR1/NR2A antagonists with somewhat higher potency. The results proved the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety to be a useful bioisoster at all three classes of iGluRs, capable of being integrated into agonists as well as antagonists.",
author = "Lolli, {Marco L} and Cecilia Giordano and Pickering, {Darryl S} and Barbara Rolando and Hansen, {Kasper B} and Antonio Foti and Alberto Contreras-Sanz and Ahmad Amir and Roberta Fruttero and Alberto Gasco and Birgitte Nielsen and Johansen, {Tommy N}",
year = "2010",
doi = "10.1021/jm1001452",
language = "English",
volume = "53",
pages = "4110--8",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues

AU - Lolli, Marco L

AU - Giordano, Cecilia

AU - Pickering, Darryl S

AU - Rolando, Barbara

AU - Hansen, Kasper B

AU - Foti, Antonio

AU - Contreras-Sanz, Alberto

AU - Amir, Ahmad

AU - Fruttero, Roberta

AU - Gasco, Alberto

AU - Nielsen, Birgitte

AU - Johansen, Tommy N

PY - 2010

Y1 - 2010

N2 - In order to investigate the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as a carboxylic acid bioisoster at ionotropic glutamate receptors (iGluRs), a series of acidic alpha-aminocarboxylic acids in which the distal carboxy group was replaced by the 4-hydroxy-1,2,5-oxadiazol-3-yl group was synthesized. Ionization constants were determined. All target compounds, except the Asp analogue 12, were resolved using chiral HPLC. Whereas 12 showed good affinity exclusively at NMDA receptors, the Glu analogue, (+)-10, was an unselective, though potent AMPA receptor preferring agonist (EC(50) = 10 microM at iGluR2) showing only low stereoselectivity. The two higher Glu homologues, (+)-15 and (+)-18, turned out to be weak agonists at iGluR2 as well as weak antagonists at NR1/NR2A, whereas the corresponding (-)-isomers were selective NR1/NR2A antagonists with somewhat higher potency. The results proved the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety to be a useful bioisoster at all three classes of iGluRs, capable of being integrated into agonists as well as antagonists.

AB - In order to investigate the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as a carboxylic acid bioisoster at ionotropic glutamate receptors (iGluRs), a series of acidic alpha-aminocarboxylic acids in which the distal carboxy group was replaced by the 4-hydroxy-1,2,5-oxadiazol-3-yl group was synthesized. Ionization constants were determined. All target compounds, except the Asp analogue 12, were resolved using chiral HPLC. Whereas 12 showed good affinity exclusively at NMDA receptors, the Glu analogue, (+)-10, was an unselective, though potent AMPA receptor preferring agonist (EC(50) = 10 microM at iGluR2) showing only low stereoselectivity. The two higher Glu homologues, (+)-15 and (+)-18, turned out to be weak agonists at iGluR2 as well as weak antagonists at NR1/NR2A, whereas the corresponding (-)-isomers were selective NR1/NR2A antagonists with somewhat higher potency. The results proved the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety to be a useful bioisoster at all three classes of iGluRs, capable of being integrated into agonists as well as antagonists.

U2 - 10.1021/jm1001452

DO - 10.1021/jm1001452

M3 - Journal article

C2 - 20408529

VL - 53

SP - 4110

EP - 4118

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 10

ER -

ID: 20122474