Derivatives of (R)-3-(5-Furanyl)carboxamido-2-aminopropanoic Acid as Potent NMDA Receptor Glycine Site Agonists with GluN2 Subunit-Specific Activity

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

Standard

Derivatives of (R)-3-(5-Furanyl)carboxamido-2-aminopropanoic Acid as Potent NMDA Receptor Glycine Site Agonists with GluN2 Subunit-Specific Activity. / Zhao, Fabao; Atxabal, Unai; Mariottini, Sofia; Yi, Feng; Lotti, James S.; Rouzbeh, Nirvan; Liu, Na; Bunch, Lennart; Hansen, Kasper B.; Clausen, Rasmus P.

In: Journal of Medicinal Chemistry, Vol. 65, No. 1, 2022, p. 734-746.

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

Harvard

Zhao, F, Atxabal, U, Mariottini, S, Yi, F, Lotti, JS, Rouzbeh, N, Liu, N, Bunch, L, Hansen, KB & Clausen, RP 2022, 'Derivatives of (R)-3-(5-Furanyl)carboxamido-2-aminopropanoic Acid as Potent NMDA Receptor Glycine Site Agonists with GluN2 Subunit-Specific Activity', Journal of Medicinal Chemistry, vol. 65, no. 1, pp. 734-746. https://doi.org/10.1021/acs.jmedchem.1c01810

APA

Zhao, F., Atxabal, U., Mariottini, S., Yi, F., Lotti, J. S., Rouzbeh, N., Liu, N., Bunch, L., Hansen, K. B., & Clausen, R. P. (2022). Derivatives of (R)-3-(5-Furanyl)carboxamido-2-aminopropanoic Acid as Potent NMDA Receptor Glycine Site Agonists with GluN2 Subunit-Specific Activity. Journal of Medicinal Chemistry, 65(1), 734-746. https://doi.org/10.1021/acs.jmedchem.1c01810

Vancouver

Zhao F, Atxabal U, Mariottini S, Yi F, Lotti JS, Rouzbeh N et al. Derivatives of (R)-3-(5-Furanyl)carboxamido-2-aminopropanoic Acid as Potent NMDA Receptor Glycine Site Agonists with GluN2 Subunit-Specific Activity. Journal of Medicinal Chemistry. 2022;65(1):734-746. https://doi.org/10.1021/acs.jmedchem.1c01810

Author

Zhao, Fabao ; Atxabal, Unai ; Mariottini, Sofia ; Yi, Feng ; Lotti, James S. ; Rouzbeh, Nirvan ; Liu, Na ; Bunch, Lennart ; Hansen, Kasper B. ; Clausen, Rasmus P. / Derivatives of (R)-3-(5-Furanyl)carboxamido-2-aminopropanoic Acid as Potent NMDA Receptor Glycine Site Agonists with GluN2 Subunit-Specific Activity. In: Journal of Medicinal Chemistry. 2022 ; Vol. 65, No. 1. pp. 734-746.

Bibtex

@article{736150fc21634ca7922945de9ebebbc6,
title = "Derivatives of (R)-3-(5-Furanyl)carboxamido-2-aminopropanoic Acid as Potent NMDA Receptor Glycine Site Agonists with GluN2 Subunit-Specific Activity",
abstract = "NMDA receptors mediate glutamatergic neurotransmission and are therapeutic targets due to their involvement in a variety of psychiatric and neurological disorders. Here, we describe the design and synthesis of a series of (R)-3-(5-furanyl)carboxamido-2-aminopropanoic acid analogues 8a–s as agonists at the glycine (Gly) binding site in the GluN1 subunit, but not GluN3 subunits, of NMDA receptors. These novel analogues display highly variable potencies and agonist efficacies among the NMDA receptor subtypes (GluN1/2A–D) in a manner dependent on the GluN2 subunit. Notably, compound 8p is identified as a potent partial agonist at GluN1/2C (EC50 = 0.074 μM) with an agonist efficacy of 28% relative to activation by Gly and virtually no agonist activity at GluN1/2A, GluN1/2B, and GluN1/2D. Thus, these novel agonists can modulate the activity of specific NMDA receptor subtypes by replacing the full endogenous agonists Gly or d-serine (d-Ser), thereby providing new opportunities in the development of novel therapeutic agents.",
author = "Fabao Zhao and Unai Atxabal and Sofia Mariottini and Feng Yi and Lotti, {James S.} and Nirvan Rouzbeh and Na Liu and Lennart Bunch and Hansen, {Kasper B.} and Clausen, {Rasmus P.}",
year = "2022",
doi = "10.1021/acs.jmedchem.1c01810",
language = "English",
volume = "65",
pages = "734--746",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "1",

}

RIS

TY - JOUR

T1 - Derivatives of (R)-3-(5-Furanyl)carboxamido-2-aminopropanoic Acid as Potent NMDA Receptor Glycine Site Agonists with GluN2 Subunit-Specific Activity

AU - Zhao, Fabao

AU - Atxabal, Unai

AU - Mariottini, Sofia

AU - Yi, Feng

AU - Lotti, James S.

AU - Rouzbeh, Nirvan

AU - Liu, Na

AU - Bunch, Lennart

AU - Hansen, Kasper B.

AU - Clausen, Rasmus P.

PY - 2022

Y1 - 2022

N2 - NMDA receptors mediate glutamatergic neurotransmission and are therapeutic targets due to their involvement in a variety of psychiatric and neurological disorders. Here, we describe the design and synthesis of a series of (R)-3-(5-furanyl)carboxamido-2-aminopropanoic acid analogues 8a–s as agonists at the glycine (Gly) binding site in the GluN1 subunit, but not GluN3 subunits, of NMDA receptors. These novel analogues display highly variable potencies and agonist efficacies among the NMDA receptor subtypes (GluN1/2A–D) in a manner dependent on the GluN2 subunit. Notably, compound 8p is identified as a potent partial agonist at GluN1/2C (EC50 = 0.074 μM) with an agonist efficacy of 28% relative to activation by Gly and virtually no agonist activity at GluN1/2A, GluN1/2B, and GluN1/2D. Thus, these novel agonists can modulate the activity of specific NMDA receptor subtypes by replacing the full endogenous agonists Gly or d-serine (d-Ser), thereby providing new opportunities in the development of novel therapeutic agents.

AB - NMDA receptors mediate glutamatergic neurotransmission and are therapeutic targets due to their involvement in a variety of psychiatric and neurological disorders. Here, we describe the design and synthesis of a series of (R)-3-(5-furanyl)carboxamido-2-aminopropanoic acid analogues 8a–s as agonists at the glycine (Gly) binding site in the GluN1 subunit, but not GluN3 subunits, of NMDA receptors. These novel analogues display highly variable potencies and agonist efficacies among the NMDA receptor subtypes (GluN1/2A–D) in a manner dependent on the GluN2 subunit. Notably, compound 8p is identified as a potent partial agonist at GluN1/2C (EC50 = 0.074 μM) with an agonist efficacy of 28% relative to activation by Gly and virtually no agonist activity at GluN1/2A, GluN1/2B, and GluN1/2D. Thus, these novel agonists can modulate the activity of specific NMDA receptor subtypes by replacing the full endogenous agonists Gly or d-serine (d-Ser), thereby providing new opportunities in the development of novel therapeutic agents.

U2 - 10.1021/acs.jmedchem.1c01810

DO - 10.1021/acs.jmedchem.1c01810

M3 - Journal article

C2 - 34918931

VL - 65

SP - 734

EP - 746

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 1

ER -

ID: 287175399