(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 contributionposted on 17.07.2002, 00:00 by Iván Collado, Concepción Pedregal, Angel Mazón, Juan Félix Espinosa, Jaime Blanco-Urgoiti, Darryle D. Schoepp, Rebecca A. Wright, Bryan G. Johnson, Ann E. Kingston
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.
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requirementglycinebicyclic systemsgroup 2 metabotropric glutamate receptorsAnxiolytic Propertiessynthesissystemically 4 ordersCarboxySelective Metabotropic Group 2 Receptor Agonistcenterbicyclic system LY 354740.group 2 mGluRs agonistsepimercarboxyanxietyGlycineCompound 7Potentcomplexitymagnitudemodelconformationally