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 - http://www.scopus.com/inward/record.url?scp=80455137237&partnerID=8YFLogxK
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 -