Synthesis and studies on the mGluR agonist activity of FAP4 stereoisomers. Issue 12 (15th June 2015)

• Record Type: Journal Article
• Authors: Ivashkin, Pavel; Lemonnier, Gérald; Tora, Amélie S.; Pin, Jean-Philippe; Goudet, Cyril; Jubault, Philippe; Pannecoucke, Xavier
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 12(2015)
• Page Start: 2523
• Page End: 2526
• Publication Date: 2015-06-15
• Subjects: Metabotropic glutamate receptor -- Fluorine -- Amino-acids -- Cyclopropane -- Phosphonic acid; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.04.043
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The four stereoisomers of 1-amino-2-fluoro-2-(phosphonomethyl)cyclopropane-1-carboxylic acid (FAP4) were synthesized via diastereoselective Rh(II)-catalysed cyclopropanation of a phosphonylated fluoroalkene. Different isomers of FAP4 and the corresponding non-fluorinated analogs showed a similar pharmacological profile against the isoforms of metabotropic glutamate receptor (mGluR). Within the fluorinated series, (−)-( Z )-FAP4 and (−)-( E )-FAP4 demonstrated the highest agonist activity against mGlu4 (EC50 0.10 μM). Our results suggest that fluorocyclopropanes bearing an amino-acid function can be suitable for the development of potent conformationally restricted mGluR agonists.