Metabotropic glutamate receptors: potential therapeutic applications of recently disclosed new chemical entities

Glutamate is the main excitatory neurotransmitter in the mammalian CNS and it exerts its action through ionotropic and metabotropic receptors. Whereas ion channels have been heavily exploited in the recent past, metabotropic glutamate receptor (mGlu) research has been hampered by the lack of potent and selective molecules with 'drug-like' structures. A new wave of ligands has recently been disclosed by a number of pharmaceutical companies highlighting the great interest around these potential therapeutic targets. This review endeavours to provide the reader with an updated and detailed panorama of the patent literature of this exciting field, also tackling non-competitive and allosteric modulators. Those skilled in the art know that it is quite difficult to extract structure-activity relationship (SAR) information from a patent or to draw 'definitive' conclusions on a compound if biological data are not specifically provided. Accordingly, the main aim of this review will be to provide the reader with the most relevant information available and to report the structures of the newly unveiled chemical entities. Other very interesting compounds recently disclosed in the primary literature will not be exhaustively covered here, but they are surely worth a further check in the available literature databases, a few examples will be mentioned only where a novel therapeutic area is disclosed or if major insights are provided.