Document Report Card

Basic Information

ID: ALA3425503

Journal: Bioorg Med Chem Lett

Title: Synthesis and studies on the mGluR agonist activity of FAP4 stereoisomers.

Authors: Ivashkin P, Lemonnier G, Tora AS, Pin JP, Goudet C, Jubault P, Pannecoucke X.

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.

CiteXplore: 25958247

DOI: 10.1016/j.bmcl.2015.04.043