A highly selective agonist for the metabotropic glutamate receptor mGluR2

Simon D. Nielsen; Marica Fulco; Michaela Serpi; Birgitte Nielsen; Maria B. Hansen; Kasper L. Hansen; Christian Thomsen; Robb Brodbeck; Hans Bräuner-Osborne; Roberto Pellicciari; Per Ola Norrby; Jeremy R. Greenwood; Rasmus P. Clausen

doi:10.1039/c1md00186h

A highly selective agonist for the metabotropic glutamate receptor mGluR2

Simon D. Nielsen
, Marica Fulco
, Michaela Serpi
, Birgitte Nielsen
, Maria B. Hansen
, Kasper L. Hansen
, Christian Thomsen
, Robb Brodbeck
, Hans Bräuner-Osborne
, Roberto Pellicciari
, Per Ola Norrby
, Jeremy R. Greenwood
, Rasmus P. Clausen

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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
Pages (from-to)	1120-1124
Number of pages	5
Journal	MedChemComm
Volume	2
Issue number	11
DOIs	https://doi.org/10.1039/c1md00186h
State	Published - Nov 2011

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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.",

author = "Nielsen, \{Simon D.\} and Marica Fulco and Michaela Serpi and Birgitte Nielsen and Hansen, \{Maria B.\} and Hansen, \{Kasper L.\} and Christian Thomsen and Robb Brodbeck and Hans Br{\"a}uner-Osborne and Roberto Pellicciari and Norrby, \{Per Ola\} and Greenwood, \{Jeremy R.\} and Clausen, \{Rasmus P.\}",

year = "2011",

month = nov,

doi = "10.1039/c1md00186h",

language = "English",

volume = "2",

pages = "1120--1124",

journal = "MedChemComm",

issn = "2040-2503",

publisher = "Royal Society of Chemistry",

number = "11",

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TY - JOUR

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

AU - Nielsen, Simon D.

AU - Fulco, Marica

AU - Serpi, Michaela

AU - Nielsen, Birgitte

AU - Hansen, Maria B.

AU - Hansen, Kasper L.

AU - Thomsen, Christian

AU - Brodbeck, Robb

AU - Bräuner-Osborne, Hans

AU - Pellicciari, Roberto

AU - Norrby, Per Ola

AU - Greenwood, Jeremy R.

AU - Clausen, Rasmus P.

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.

UR - https://www.scopus.com/pages/publications/80455137237

U2 - 10.1039/c1md00186h

DO - 10.1039/c1md00186h

M3 - Article

AN - SCOPUS:80455137237

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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