The asymmetric synthesis and biological activity of (2S,1′S,2′S,3′R)-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.
CITATION STYLE
Collado, I., Pedregal, C., Mazón, A., Espinosa, J. F., Blanco-Urgoiti, J., Schoepp, D. D., … Kingston, A. E. (2002). (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. Journal of Medicinal Chemistry, 45(17), 3619–3629. https://doi.org/10.1021/jm0110486
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