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

• Published in: Bioorganic & medicinal chemistry letters 1998-10, Vol.8 (20), p.2849-2854
• Main Authors: Collado, Iván, Ezquerra, Jesús, Mazón, Angel, Pedregal, Concepción, Yruretagoyena, Belén, Kingston, Anne E., Tomlinson, Rosemary, Wright, Rebecca A., Johnson, Bryan G., Schoepp, Darryle D.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Line; Cyclopropanes - chemistry; Cyclopropanes - pharmacology; Excitatory Amino Acid Antagonists - chemical synthesis; Excitatory Amino Acid Antagonists - pharmacology; Glutamatergic system (aspartate and other excitatory aminoacids); Glycine - analogs & derivatives; Glycine - chemistry; Glycine - pharmacology; Humans; Inhibitory Concentration 50; Medical sciences; Neurons - drug effects; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Prosencephalon - drug effects; Rats; Receptors, Glutamate - drug effects; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00510-1

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 (IC 50 values greater than 100μm). A series of carboxycyclopropylglycines with two substituents at the alpha and C-3′ positions was prepared as selective metabotropic glutamate receptor antagonists.