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

The first series of 2′-substituted 2-(3′-carboxybicydo-[1.1.1] pentyl)glycine derivatives, (2R)- and (2S)-(2′,2′-dichloro-3′- carboxybicydo[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. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.