title: Α-amino-β-fluorocyclopropanecarboxylic acids as a new tool for drug development: synthesis of glutamic acid analogs and agonist activity towards metabotropic glutamate receptor 4.
abstract: Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM.
authors: INSA de Rouen and Université de Rouen, CNRS, UMR 6014 & FR 3038, COBRA, IRCOF, 1 rue Tesnière, 76821 Mont-Saint-Aignan Cedex, France.
authors: Gérald
authors: G
authors: Lemonnier
authors: Cédric
authors: C
authors: Lion
authors: Jean-Charles
authors: JC
authors: Quirion
authors: Jean-Philippe
authors: JP
authors: Pin
authors: Cyril
authors: C
authors: Goudet
authors: Philippe
authors: P
authors: Jubault
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D018698:Glutamic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D011994:Recombinant Proteins / Q000819:agonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D003521:Cyclopropanes; D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; C576629:alpha-amino-beta-fluorocyclopropanecarboxylic acid; D018698:Glutamic Acid; C108823:metabotropic glutamate receptor 4