A highly selective agonist for the metabotropic glutamate receptor mGluR2

Simon Dalsgaard Nielsen; Marica Fulco; Michaela Serpi; Birgitte Nielsen; Maria Brinck  Hansen; Kasper Lind Hansen; Christian Thomsen; Robb Brodbeck; Hans Bräuner-Osborne; Roberto Pellicciari; Per-Ola Norrby; Jeremy R Greenwood; Rasmus Prætorius Clausen

doi:10.1039/c1md00186h

A highly selective agonist for the metabotropic glutamate receptor mGluR2

Simon Dalsgaard Nielsen, Marica Fulco, Michaela Serpi, Birgitte Nielsen, Maria Brinck Hansen, Kasper Lind Hansen, Christian Thomsen, Robb Brodbeck, Hans Bräuner-Osborne, Roberto Pellicciari, Per-Ola Norrby, Jeremy R Greenwood, Rasmus Prætorius Clausen

6 Citations (Scopus)

Abstract

The three conformationally restricted cyclopropyl glutamate analogues (3, 4, 5) were synthesised and their affinity for ionotropic and activity at metabotropic glutamate receptors were probed. Compound 4 turned out to be a highly selective agonist at the metabotropic glutamate receptor mGluR2 with at least two orders of magnitude selectivity in potency compared to the very homologous mGluR3 as well as mGluR1, 4, 5, 7. We also tried to synthesise the two epimers of 6, but the two compounds underwent fast epimerisation in H ₂O. Furthermore, two cyclopropyl arginine analogues (7, 8) were synthesised and characterised pharmacologically at GPRC6A.

Original language	English
Journal	MedChemComm
Volume	2
Issue number	11
Pages (from-to)	1120-1124
ISSN	2040-2503
DOIs	https://doi.org/10.1039/c1md00186h
Publication status	Published - Nov 2011

Keywords

Former Faculty of Pharmaceutical Sciences

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title = "A highly selective agonist for the metabotropic glutamate receptor mGluR2",

abstract = "The three conformationally restricted cyclopropyl glutamate analogues (3, 4, 5) were synthesised and their affinity for ionotropic and activity at metabotropic glutamate receptors were probed. Compound 4 turned out to be a highly selective agonist at the metabotropic glutamate receptor mGluR2 with at least two orders of magnitude selectivity in potency compared to the very homologous mGluR3 as well as mGluR1, 4, 5, 7. We also tried to synthesise the two epimers of 6, but the two compounds underwent fast epimerisation in H 2O. Furthermore, two cyclopropyl arginine analogues (7, 8) were synthesised and characterised pharmacologically at GPRC6A.",

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author = "Nielsen, {Simon Dalsgaard} and Marica Fulco and Michaela Serpi and Birgitte Nielsen and Hansen, {Maria Brinck} and Hansen, {Kasper Lind} and Christian Thomsen and Robb Brodbeck and Hans Br{\"a}uner-Osborne and Roberto Pellicciari and Per-Ola Norrby and Greenwood, {Jeremy R} and Clausen, {Rasmus Pr{\ae}torius}",

year = "2011",

month = nov,

doi = "10.1039/c1md00186h",

language = "English",

volume = "2",

pages = "1120--1124",

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T1 - A highly selective agonist for the metabotropic glutamate receptor mGluR2

AU - Nielsen, Simon Dalsgaard

AU - Fulco, Marica

AU - Serpi, Michaela

AU - Nielsen, Birgitte

AU - Hansen, Maria Brinck

AU - Hansen, Kasper Lind

AU - Thomsen, Christian

AU - Brodbeck, Robb

AU - Bräuner-Osborne, Hans

AU - Pellicciari, Roberto

AU - Norrby, Per-Ola

AU - Greenwood, Jeremy R

AU - Clausen, Rasmus Prætorius

PY - 2011/11

Y1 - 2011/11

N2 - The three conformationally restricted cyclopropyl glutamate analogues (3, 4, 5) were synthesised and their affinity for ionotropic and activity at metabotropic glutamate receptors were probed. Compound 4 turned out to be a highly selective agonist at the metabotropic glutamate receptor mGluR2 with at least two orders of magnitude selectivity in potency compared to the very homologous mGluR3 as well as mGluR1, 4, 5, 7. We also tried to synthesise the two epimers of 6, but the two compounds underwent fast epimerisation in H 2O. Furthermore, two cyclopropyl arginine analogues (7, 8) were synthesised and characterised pharmacologically at GPRC6A.

AB - The three conformationally restricted cyclopropyl glutamate analogues (3, 4, 5) were synthesised and their affinity for ionotropic and activity at metabotropic glutamate receptors were probed. Compound 4 turned out to be a highly selective agonist at the metabotropic glutamate receptor mGluR2 with at least two orders of magnitude selectivity in potency compared to the very homologous mGluR3 as well as mGluR1, 4, 5, 7. We also tried to synthesise the two epimers of 6, but the two compounds underwent fast epimerisation in H 2O. Furthermore, two cyclopropyl arginine analogues (7, 8) were synthesised and characterised pharmacologically at GPRC6A.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1039/c1md00186h

DO - 10.1039/c1md00186h

M3 - Journal article

SN - 2040-2503

VL - 2

SP - 1120

EP - 1124

JO - MedChemComm

JF - MedChemComm

IS - 11

ER -

A highly selective agonist for the metabotropic glutamate receptor mGluR2

Abstract

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