Synthesis and Preliminary Biological Evaluation of 2′‐Substituted 2‐(3′‐Carboxybicyclo[1.1.1]pentyl)glycine Derivatives as Group I Selective Metabotropic Glutamate Receptor Ligands

Abstract

The first series of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives, (2R)- and (2S)-(2',2'-dichloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (10) and (11), and 2-(2'-chloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (12) were synthesized and evaluated as mGluR ligands. Compounds 11 and 12 were shown to be competitive group I mGluR antagonists. These results are also discussed in light of docking studies with both the active (closed) and inactive (open) conformations of mGluR1.