Revisiting the Quinoxalinedione scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors.

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

Standard

Revisiting the Quinoxalinedione scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors. / Demmer, Charles Sylvain; Rombach, David; Liu, Na; Nielsen, Birgitte; Pickering, Darryl S; Bunch, Lennart.

In: A C S Chemical Neuroscience, Vol. 8, No. 11, 01.12.2017, p. 2477-2495.

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

Harvard

Demmer, CS, Rombach, D, Liu, N, Nielsen, B, Pickering, DS & Bunch, L 2017, 'Revisiting the Quinoxalinedione scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors.', A C S Chemical Neuroscience, vol. 8, no. 11, pp. 2477-2495. https://doi.org/10.1021/acschemneuro.7b00243

APA

Demmer, C. S., Rombach, D., Liu, N., Nielsen, B., Pickering, D. S., & Bunch, L. (2017). Revisiting the Quinoxalinedione scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors. A C S Chemical Neuroscience, 8(11), 2477-2495. https://doi.org/10.1021/acschemneuro.7b00243

Vancouver

Demmer CS, Rombach D, Liu N, Nielsen B, Pickering DS, Bunch L. Revisiting the Quinoxalinedione scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors. A C S Chemical Neuroscience. 2017 Dec 1;8(11):2477-2495. https://doi.org/10.1021/acschemneuro.7b00243

Author

Demmer, Charles Sylvain ; Rombach, David ; Liu, Na ; Nielsen, Birgitte ; Pickering, Darryl S ; Bunch, Lennart. / Revisiting the Quinoxalinedione scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors. In: A C S Chemical Neuroscience. 2017 ; Vol. 8, No. 11. pp. 2477-2495.

Bibtex

@article{3c2ef362459044ebb0f82a8403408924,
title = "Revisiting the Quinoxalinedione scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors.",
abstract = "More than two decades ago, the quinoxalinedione scaffold was shown to act as an α-amino acid bioisoster. Following extensive structure-activity-relationship (SAR) studies, the antagonists DNQX, CNQX, and NBQX in the ionotropic glutamate receptor field were identified. In this work we revisit the quinoxalinedione scaffold and explore the incorporation of an acid functionality in the 6-position. The SAR studies disclose that by this strategy it was possible to tune in iGluR selectivity amongst the AMPA, NMDA and KA receptors, and to some extent also obtain full receptor subtype selectivity. Highlights of the study of 44 new analogs are compound 2m being a high affinity ligand for native AMPA receptors (IC50= 0.48 µM), analogs 2e,f,h,k,v all displayed selectivity for native NMDA receptors, compounds 2s,t,u are selective ligand for the GluK1 receptor. Most interestingly compound 2w was shown to be a GluK3-preferring ligand with full selectivity over native AMPA, KA and NMDA receptors.",
author = "Demmer, {Charles Sylvain} and David Rombach and Na Liu and Birgitte Nielsen and Pickering, {Darryl S} and Lennart Bunch",
year = "2017",
month = dec,
day = "1",
doi = "10.1021/acschemneuro.7b00243",
language = "English",
volume = "8",
pages = "2477--2495",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "11",

}

RIS

TY - JOUR

T1 - Revisiting the Quinoxalinedione scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors.

AU - Demmer, Charles Sylvain

AU - Rombach, David

AU - Liu, Na

AU - Nielsen, Birgitte

AU - Pickering, Darryl S

AU - Bunch, Lennart

PY - 2017/12/1

Y1 - 2017/12/1

N2 - More than two decades ago, the quinoxalinedione scaffold was shown to act as an α-amino acid bioisoster. Following extensive structure-activity-relationship (SAR) studies, the antagonists DNQX, CNQX, and NBQX in the ionotropic glutamate receptor field were identified. In this work we revisit the quinoxalinedione scaffold and explore the incorporation of an acid functionality in the 6-position. The SAR studies disclose that by this strategy it was possible to tune in iGluR selectivity amongst the AMPA, NMDA and KA receptors, and to some extent also obtain full receptor subtype selectivity. Highlights of the study of 44 new analogs are compound 2m being a high affinity ligand for native AMPA receptors (IC50= 0.48 µM), analogs 2e,f,h,k,v all displayed selectivity for native NMDA receptors, compounds 2s,t,u are selective ligand for the GluK1 receptor. Most interestingly compound 2w was shown to be a GluK3-preferring ligand with full selectivity over native AMPA, KA and NMDA receptors.

AB - More than two decades ago, the quinoxalinedione scaffold was shown to act as an α-amino acid bioisoster. Following extensive structure-activity-relationship (SAR) studies, the antagonists DNQX, CNQX, and NBQX in the ionotropic glutamate receptor field were identified. In this work we revisit the quinoxalinedione scaffold and explore the incorporation of an acid functionality in the 6-position. The SAR studies disclose that by this strategy it was possible to tune in iGluR selectivity amongst the AMPA, NMDA and KA receptors, and to some extent also obtain full receptor subtype selectivity. Highlights of the study of 44 new analogs are compound 2m being a high affinity ligand for native AMPA receptors (IC50= 0.48 µM), analogs 2e,f,h,k,v all displayed selectivity for native NMDA receptors, compounds 2s,t,u are selective ligand for the GluK1 receptor. Most interestingly compound 2w was shown to be a GluK3-preferring ligand with full selectivity over native AMPA, KA and NMDA receptors.

U2 - 10.1021/acschemneuro.7b00243

DO - 10.1021/acschemneuro.7b00243

M3 - Journal article

C2 - 28872835

VL - 8

SP - 2477

EP - 2495

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 11

ER -

ID: 182579722