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
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Jun 15; Vol. 25 (12), pp. 2523-6. Date of Electronic Publication: 2015 Apr 22.
Publication Year :: 2015
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.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)