Recent Advances in the Discovery of Selective AMPA Receptor Positive Allosteric Modulators

Simon      E. Ward; Mark      Harries

doi:10.2174/092986710792927840

Abstract

This article highlights recent advances in the discovery of new positive allosteric modulators of the AMPA receptor, excluding compounds of thiadiazine chemotype, most of which were developed by Servier and the University of Liege. The field of AMPA receptor modulators continues to be a fertile area for the discovery of new potential therapeutic agents, and recent years have seen a marked diversification in the range of chemotypes prepared. An overview is also given of the recent key new biological data.

Keywords: AMPA receptor, AMPA positive modulator, thiadiazine chemotype, glutamatergic neurotransmitter system, neurodegenerative diseases, schizophrenia,Alzheimer's disease, Parkinson's disease, postsynaptic membrane, tetrameric complex, AMPAR complex, synaptic plasticity, glutamate bound dimer, benzothiadiazines, cornichon proteins, deactivation kinetics, cystine-knot AMPAR, cognitive performance, preclinical behavioural testing, chemotypes, trifluoromethylpyrazole, D-amphetamine-stimulated locomotion, Phenethyl Sulfonamide Series, aromatic thiophene linker, cell voltage-clamp electrophysiology, FLIPR-based assays, Cyclopropane Derivatives, FLUO-4, HEK293, indane core structure, Pyrrole/Thiophene Acid Series, Iminothiazole, Trifluoromethylpyrazole Series