title: Determination of the absolute configuration of phosphinic analogues of glutamate.
abstract: A series of phosphinic glutamate derivatives (e.g.LSP1-2111) have been proven to be potent agonists of metabotropic glutamate (mGlu) receptors and shown promising in vivo activity. However, so far all were synthesized and tested as a mixture of two diastereomers whose absolute and relative configurations are not known. In this study, the stereomers were separated on a Crownpack CR(+) column and their absolute configuration was assessed by means of a diastereoselective synthesis. Both separated L-stereomers activated the mGlu4 receptor with EC50's of 0.72 and 4.4 μM for (1S,1'S)-and (1S,1'R)-LSP1-2111, respectively.
authors.affiliation: Laboratoire de Chimie & Biochimie Pharmacologiques et Toxicologiques, UMR CNRS 8601, Université Paris Descartes, Sorbonne Paris Cité, 45, rue des Saints-Pères 75270, Paris cedex 06, France. francine.acher@parisdescartes.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Commare
authors.forename: Delphine
authors.initials: D
authors.lastname: Rigault
authors.forename: Isabelle A
authors.initials: IA
authors.lastname: Lemasson
authors.forename: Patrick
authors.initials: P
authors.lastname: Deschamps
authors.forename: Alain
authors.initials: A
authors.lastname: Tomas
authors.forename: Pascal
authors.initials: P
authors.lastname: Roussel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brabet
authors.forename: Cyril
authors.initials: C
authors.lastname: Goudet
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Pin
authors.forename: Frédéric R
authors.initials: FR
authors.lastname: Leroux
authors.forename: Françoise
authors.initials: F
authors.lastname: Colobert
authors.forename: Francine C
authors.initials: FC
authors.lastname: Acher
mesh_terms: D018698:Glutamic Acid / Q000737:chemistry* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000737:chemistry*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists
chemical_list: D009943:Organophosphorus Compounds; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid