Design and synthesis of APTCs (aminopyrrolidinetricarboxylic acids): identification of a new group III metabotropic glutamate receptor selective agonist

  • Bioorg Med Chem Lett. 2006 Sep 15;16(18):4856-60. doi: 10.1016/j.bmcl.2006.06.062.
Stephan Schann  1 ,  Christel Menet ,  Paul Arvault ,  Géraldine Mercier ,  Mélanie Frauli ,  Stanislas Mayer ,  Nadia Hubert ,  Nicolas Triballeau ,  Hugues-Olivier Bertrand ,  Francine Acher ,  Pascal Neuville
Affiliations
  • 1. Faust Pharmaceuticals, BIOPARC, Boulevard Sebastien Brant, 67400 Illkirch, France. [email protected]
PMID: 16828551 DOI: 10.1016/j.bmcl.2006.06.062
Abstract

A new family of mGlu receptor orthosteric ligands called APTCs was designed and synthesized using a parallel chemistry approach. Amongst 65 molecules tested on mGlu4, mGlu6 and mGlu8 subtypes, (2S,4S)-4-amino-1-[(E)-3-carboxyacryloyl]pyrrolidine-2,4-dicarboxylic acid (8a06-FP0429) has been shown to be a full mGlu4 agonist and a partial mGlu8 agonist. In addition, 8a06 was shown to be selective versus group I and II mGlu subtypes. A possible explanation for this efficacy difference is proposed by docking experiment performed with molecular model of the receptor.

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