title: Design and synthesis of APTCs (aminopyrrolidinetricarboxylic acids): identification of a new group III metabotropic glutamate receptor selective agonist.
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.
authors.affiliation: Faust Pharmaceuticals, BIOPARC, Boulevard Sebastien Brant, 67400 Illkirch, France. sschann@faustpharma.com
authors.forename: Stephan
authors.initials: S
authors.lastname: Schann
authors.forename: Christel
authors.initials: C
authors.lastname: Menet
authors.forename: Paul
authors.initials: P
authors.lastname: Arvault
authors.forename: Géraldine
authors.initials: G
authors.lastname: Mercier
authors.forename: Mélanie
authors.initials: M
authors.lastname: Frauli
authors.forename: Stanislas
authors.initials: S
authors.lastname: Mayer
authors.forename: Nadia
authors.initials: N
authors.lastname: Hubert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Triballeau
authors.forename: Hugues-Olivier
authors.initials: HO
authors.lastname: Bertrand
authors.forename: Francine
authors.initials: F
authors.lastname: Acher
authors.forename: Pascal
authors.initials: P
authors.lastname: Neuville
mesh_terms: D000586:Amination; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011759:Pyrrolidines / Q000737:chemistry*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D011759:Pyrrolidines; D018094:Receptors, Metabotropic Glutamate; C032519:pyrrolidine; D002118:Calcium