(2S,1′S,2′S,3′R)-2-(2′-carboxy-3′-methylcyclopropyl) glycine is a potent and selective metabotropic group 2 receptor agonist with anxiolytic properties

The asymmetric synthesis and biological activity of (2S,1'S,2'S,3R)-2-(2'-carboxy-3'-methylcyclopropyl) glycine 7 and its epimer at the C3' center 6 are described. Compound 7 is a highly potent and selective agonist for group 2 metabotropric glutamate receptors (mGluRs). It is also systemically 4 orders of magnitude more active in the fear-potentiated startle model of anxiety in rats than the rigid constrained bicyclic system LY354740. Therefore, we have shown that high molecular complexity of conformationally constrained bicyclic systems is not a requirement to achieve highly selective and potent group 2 mGluRs agonists.