2,3′-disubstituted-2-(2′-carboxycyclopropyl)glycines as potent and selective antagonists of metabotropic glutamate receptors

2-(9-Xanthylmethyl)-2-(2′-carboxycyclopropyl) glycine 6e is a novel metabotropic glutamate receptor antagonist. A series of alpha, C-3′ disubstituted (carboxycyclopropyl)glycines 6f-n were prepared. Antagonist activity was observed for all these compounds at group 2 and group 3 mGluRs. Although they were slightly less active on group 2 mGluRs than non C-3′ substituted 6e, the compounds 6f-n were more selective with lesser or no activity on group 1 mGluR subtypes (IC50 values greater than 100μm).