L-(+)-thioAP4, New Group III mGluR Agonist
Journal of Medicinal Chemistry, 2007, Vol. 50, No. 19 4663
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T.; Inderbitzin, W.; Laurie, D.; Sommer, B.; Varney, M. A.;
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(0.1 M) containing 10% of Triton X100 (Sigma). The resulting
solution was then collected in a 96-well sample plate and mixed
with liquid scintillator. Radioactivity was counted using a
Wallac 1450 Microbeta stintillation and luminescence counter
(Perkin-Elmer). Results are expressed as the ratio of IP to the total
radioactivity corresponding to IP plus membrane (Figure 2). All
points are realized in triplicate. The dose-response curves were fitted
using the GraphPad Prism program and the following equation:
y ) [(ymax - ymin)/(1 + (x/EC50)n)] + ymin, where EC50 is the
concentration of the compound necessary to obtain the half-maximal
effect and n is the Hill coefficient.
Phosphonophenylglycine,
a potent and selective group III
metabotropic glutamate receptor agonist, is anticonvulsive and
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Acknowledgment. This work was supported by the CNRS,
INSERM, the Fe´de´ration pour la Recherche sur le Cerveau, the
Agence Nationale pour la Recherche (Grant ANR-05-NEUR-
0121-04), and the Fondation de France, Comite´ Parkinson (Grant
No. 580062). The authors also thank for its technical support
the Plateforme IFR3 Pharmacologie-Interactome at Montpellier
and the Re´gion Languedoc-Roussillon. We are also grateful to
Delphine Leclaire (UMR8601) for her technical assistance,
Hugues-Olivier Bertrand (Accelrys Inc.), and Nicolas Triballeau
(UMR8601, Accelrys Inc.) for their continuous help in molecular
modeling.
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Supporting Information Available: Chart S1, structures of
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1
and PPG); H NMR, 13C NMR, 31P NMR, and mass spectra of 1,
2, and 4; sequence alignment of the eight mGlu receptors;
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traces. This material is available free of charge via the Internet at
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