New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III

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

Standard

New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III. / Huynh, Tri H. V.; Erichsen, Mette N.; Tora, Amelie S.; Goudet, Cyril; Sagot, Emmanuelle; Assaf, Zeinab; Thomsen, Christian; Brodbeck, Robb; Stensbol, Tine B.; Bjorn-Yoshimoto, Walden E.; Nielsen, Birgitte; Pin, Jean-Philippe; Gefflaut, Thierry; Bunch, Lennart.

In: Journal of Medicinal Chemistry, Vol. 59, No. 3, 2016, p. 914-924.

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

Harvard

Huynh, THV, Erichsen, MN, Tora, AS, Goudet, C, Sagot, E, Assaf, Z, Thomsen, C, Brodbeck, R, Stensbol, TB, Bjorn-Yoshimoto, WE, Nielsen, B, Pin, J-P, Gefflaut, T & Bunch, L 2016, 'New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III', Journal of Medicinal Chemistry, vol. 59, no. 3, pp. 914-924. https://doi.org/10.1021/acs.jmedchem.5b01333

APA

Huynh, T. H. V., Erichsen, M. N., Tora, A. S., Goudet, C., Sagot, E., Assaf, Z., Thomsen, C., Brodbeck, R., Stensbol, T. B., Bjorn-Yoshimoto, W. E., Nielsen, B., Pin, J-P., Gefflaut, T., & Bunch, L. (2016). New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III. Journal of Medicinal Chemistry, 59(3), 914-924. https://doi.org/10.1021/acs.jmedchem.5b01333

Vancouver

Huynh THV, Erichsen MN, Tora AS, Goudet C, Sagot E, Assaf Z et al. New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III. Journal of Medicinal Chemistry. 2016;59(3):914-924. https://doi.org/10.1021/acs.jmedchem.5b01333

Author

Huynh, Tri H. V. ; Erichsen, Mette N. ; Tora, Amelie S. ; Goudet, Cyril ; Sagot, Emmanuelle ; Assaf, Zeinab ; Thomsen, Christian ; Brodbeck, Robb ; Stensbol, Tine B. ; Bjorn-Yoshimoto, Walden E. ; Nielsen, Birgitte ; Pin, Jean-Philippe ; Gefflaut, Thierry ; Bunch, Lennart. / New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III. In: Journal of Medicinal Chemistry. 2016 ; Vol. 59, No. 3. pp. 914-924.

Bibtex

@article{bf5679fb2baa446b986db5b6c6839a34,
title = "New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III",
abstract = "The metabotropic glutamate (Glu) receptors (mGluRs) play key roles in modulating excitatory neurotransmission in the brain. In all, eight subtypes have been identified and divided into three groups, group I (mGlu1,5), group II (mGlu2,3), and group III (mGlu4,6–8). In this article, we present a L-2,4-syn-substituted Glu analogue, 1d, which displays selective agonist activity at mGlu2 over the remaining mGluR subtypes. A modeling study and redesign of the core scaffold led to the stereoselective synthesis of four new conformationally restricted Glu analogues, 2a–d. Most interestingly, 2a retained a selective agonist activity profile at mGlu2 (EC50 in the micromolar range), whereas 2c/2d were both selective agonists at group III, subtypes mGlu4,6,8. In general, 2d was 20-fold more potent than 2c and potently activated mGlu4,6,8 in the low–mid nanomolar range.",
author = "Huynh, {Tri H. V.} and Erichsen, {Mette N.} and Tora, {Amelie S.} and Cyril Goudet and Emmanuelle Sagot and Zeinab Assaf and Christian Thomsen and Robb Brodbeck and Stensbol, {Tine B.} and Bjorn-Yoshimoto, {Walden E.} and Birgitte Nielsen and Jean-Philippe Pin and Thierry Gefflaut and Lennart Bunch",
year = "2016",
doi = "10.1021/acs.jmedchem.5b01333",
language = "English",
volume = "59",
pages = "914--924",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "3",

}

RIS

TY - JOUR

T1 - New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III

AU - Huynh, Tri H. V.

AU - Erichsen, Mette N.

AU - Tora, Amelie S.

AU - Goudet, Cyril

AU - Sagot, Emmanuelle

AU - Assaf, Zeinab

AU - Thomsen, Christian

AU - Brodbeck, Robb

AU - Stensbol, Tine B.

AU - Bjorn-Yoshimoto, Walden E.

AU - Nielsen, Birgitte

AU - Pin, Jean-Philippe

AU - Gefflaut, Thierry

AU - Bunch, Lennart

PY - 2016

Y1 - 2016

N2 - The metabotropic glutamate (Glu) receptors (mGluRs) play key roles in modulating excitatory neurotransmission in the brain. In all, eight subtypes have been identified and divided into three groups, group I (mGlu1,5), group II (mGlu2,3), and group III (mGlu4,6–8). In this article, we present a L-2,4-syn-substituted Glu analogue, 1d, which displays selective agonist activity at mGlu2 over the remaining mGluR subtypes. A modeling study and redesign of the core scaffold led to the stereoselective synthesis of four new conformationally restricted Glu analogues, 2a–d. Most interestingly, 2a retained a selective agonist activity profile at mGlu2 (EC50 in the micromolar range), whereas 2c/2d were both selective agonists at group III, subtypes mGlu4,6,8. In general, 2d was 20-fold more potent than 2c and potently activated mGlu4,6,8 in the low–mid nanomolar range.

AB - The metabotropic glutamate (Glu) receptors (mGluRs) play key roles in modulating excitatory neurotransmission in the brain. In all, eight subtypes have been identified and divided into three groups, group I (mGlu1,5), group II (mGlu2,3), and group III (mGlu4,6–8). In this article, we present a L-2,4-syn-substituted Glu analogue, 1d, which displays selective agonist activity at mGlu2 over the remaining mGluR subtypes. A modeling study and redesign of the core scaffold led to the stereoselective synthesis of four new conformationally restricted Glu analogues, 2a–d. Most interestingly, 2a retained a selective agonist activity profile at mGlu2 (EC50 in the micromolar range), whereas 2c/2d were both selective agonists at group III, subtypes mGlu4,6,8. In general, 2d was 20-fold more potent than 2c and potently activated mGlu4,6,8 in the low–mid nanomolar range.

U2 - 10.1021/acs.jmedchem.5b01333

DO - 10.1021/acs.jmedchem.5b01333

M3 - Journal article

C2 - 26814576

VL - 59

SP - 914

EP - 924

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -

ID: 160187527