Literature

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.

DOI： 10.1016/j.bmcl.2015.04.043

Synthesis and studies on the mGluR agonist activity of FAP4 stereoisomers

Bioorganic & Medicinal Chemistry Letters 2015.0

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

Bioorganic & Medicinal Chemistry 2012.0

Synthesis and preliminary pharmacological evaluation of the four stereoisomers of (2S)-2-(2′-phosphono-3′-phenylcyclopropyl)glycine, the first class of 3′-substituted transC1′−2′-2-(2′-phosphonocyclopropyl)glycines

Bioorganic & Medicinal Chemistry 2007.0

Synthesis, molecular modeling and preliminary biological evaluation of 1-amino-3-phosphono-3-cyclopentene-1-carboxylic acid and 1-amino-3-phosphono-2-cyclopentene-1-carboxylic acid, two novel agonists of metabotropic glutamate receptors of group III

Bioorganic & Medicinal Chemistry Letters 2000.0

Synthesis and preliminary biological evaluation of (2S,1′R,2′S)- and (2S,1′S,2′R)-2-(2′-phosphonocyclopropyl)glycines, two novel conformationally constrained l-AP4 analogues

Bioorganic & Medicinal Chemistry Letters 2006.0

A highly selective agonist for the metabotropic glutamate receptor mGluR2