N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands. / Clausen, Rasmus Prætorius; Christensen, Caspar; Hansen, Kasper Bø; Greenwood, Jeremy R; Jørgensen, Lars; Micale, Nicola; Madsen, Jens Christian; Nielsen, Birgitte; Egebjerg, Jan; Bräuner-Osborne, Hans; Traynelis, Stephen F; Kristensen, Jesper Langgaard.

In: Journal of Medicinal Chemistry, Vol. 51, No. 14, 2008, p. 4179-87.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Clausen, RP, Christensen, C, Hansen, KB, Greenwood, JR, Jørgensen, L, Micale, N, Madsen, JC, Nielsen, B, Egebjerg, J, Bräuner-Osborne, H, Traynelis, SF & Kristensen, JL 2008, 'N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands', Journal of Medicinal Chemistry, vol. 51, no. 14, pp. 4179-87. https://doi.org/10.1021/jm800025e

APA

Clausen, R. P., Christensen, C., Hansen, K. B., Greenwood, J. R., Jørgensen, L., Micale, N., ... Kristensen, J. L. (2008). N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands. Journal of Medicinal Chemistry, 51(14), 4179-87. https://doi.org/10.1021/jm800025e

Vancouver

Clausen RP, Christensen C, Hansen KB, Greenwood JR, Jørgensen L, Micale N et al. N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands. Journal of Medicinal Chemistry. 2008;51(14):4179-87. https://doi.org/10.1021/jm800025e

Author

Clausen, Rasmus Prætorius ; Christensen, Caspar ; Hansen, Kasper Bø ; Greenwood, Jeremy R ; Jørgensen, Lars ; Micale, Nicola ; Madsen, Jens Christian ; Nielsen, Birgitte ; Egebjerg, Jan ; Bräuner-Osborne, Hans ; Traynelis, Stephen F ; Kristensen, Jesper Langgaard. / N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 14. pp. 4179-87.

Bibtex

@article{5a8272e0db2e11dd9473000ea68e967b,
title = "N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands",
abstract = "A series of analogues based on N-hydroxypyrazole as a bioisostere for the distal carboxylate group of aspartate have been designed, synthesized, and pharmacologically characterized. Affinity studies on the major glutamate receptor subgroups show that these 4-substituted N-hydroxypyrazol-5-yl glycine (NHP5G) derivatives are selectively recognized by N-methyl- d-aspartic acid (NMDA) receptors and that the ( R)-enantiomers are preferred. Moreover, several of the compounds are able to discriminate between individual subtypes among the NMDA receptors, providing new pharmacological tools. For example, 4-propyl NHP5G is an antagonist at the NR1/NR2A subtype but an agonist at the NR1/NR2D subtype. Molecular docking studies indicate that the substituent protrudes into a region that may be further exploited to improve subtype selectivity, thereby opening up a design strategy for ligands which can differentiate individual NMDA receptor subtypes.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Clausen, {Rasmus Pr{\ae}torius} and Caspar Christensen and Hansen, {Kasper B{\o}} and Greenwood, {Jeremy R} and Lars J{\o}rgensen and Nicola Micale and Madsen, {Jens Christian} and Birgitte Nielsen and Jan Egebjerg and Hans Br{\"a}uner-Osborne and Traynelis, {Stephen F} and Kristensen, {Jesper Langgaard}",
note = "Keywords: Animals; Chromatography, High Pressure Liquid; Circular Dichroism; Glycine; Ligands; Models, Molecular; Patch-Clamp Techniques; Receptors, N-Methyl-D-Aspartate; Xenopus",
year = "2008",
doi = "10.1021/jm800025e",
language = "English",
volume = "51",
pages = "4179--87",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "14",

}

RIS

TY - JOUR

T1 - N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands

AU - Clausen, Rasmus Prætorius

AU - Christensen, Caspar

AU - Hansen, Kasper Bø

AU - Greenwood, Jeremy R

AU - Jørgensen, Lars

AU - Micale, Nicola

AU - Madsen, Jens Christian

AU - Nielsen, Birgitte

AU - Egebjerg, Jan

AU - Bräuner-Osborne, Hans

AU - Traynelis, Stephen F

AU - Kristensen, Jesper Langgaard

N1 - Keywords: Animals; Chromatography, High Pressure Liquid; Circular Dichroism; Glycine; Ligands; Models, Molecular; Patch-Clamp Techniques; Receptors, N-Methyl-D-Aspartate; Xenopus

PY - 2008

Y1 - 2008

N2 - A series of analogues based on N-hydroxypyrazole as a bioisostere for the distal carboxylate group of aspartate have been designed, synthesized, and pharmacologically characterized. Affinity studies on the major glutamate receptor subgroups show that these 4-substituted N-hydroxypyrazol-5-yl glycine (NHP5G) derivatives are selectively recognized by N-methyl- d-aspartic acid (NMDA) receptors and that the ( R)-enantiomers are preferred. Moreover, several of the compounds are able to discriminate between individual subtypes among the NMDA receptors, providing new pharmacological tools. For example, 4-propyl NHP5G is an antagonist at the NR1/NR2A subtype but an agonist at the NR1/NR2D subtype. Molecular docking studies indicate that the substituent protrudes into a region that may be further exploited to improve subtype selectivity, thereby opening up a design strategy for ligands which can differentiate individual NMDA receptor subtypes.

AB - A series of analogues based on N-hydroxypyrazole as a bioisostere for the distal carboxylate group of aspartate have been designed, synthesized, and pharmacologically characterized. Affinity studies on the major glutamate receptor subgroups show that these 4-substituted N-hydroxypyrazol-5-yl glycine (NHP5G) derivatives are selectively recognized by N-methyl- d-aspartic acid (NMDA) receptors and that the ( R)-enantiomers are preferred. Moreover, several of the compounds are able to discriminate between individual subtypes among the NMDA receptors, providing new pharmacological tools. For example, 4-propyl NHP5G is an antagonist at the NR1/NR2A subtype but an agonist at the NR1/NR2D subtype. Molecular docking studies indicate that the substituent protrudes into a region that may be further exploited to improve subtype selectivity, thereby opening up a design strategy for ligands which can differentiate individual NMDA receptor subtypes.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jm800025e

DO - 10.1021/jm800025e

M3 - Journal article

C2 - 18578474

VL - 51

SP - 4179

EP - 4187

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 14

ER -

ID: 9511537