Ring-Fused Thiadiazines as Core Structures for the Development of Potent AMPA Receptor Potentiators

B.      Pirotte; P.      Francotte; E.      Goffin; P.      Fraikin; L.      Danober; B.      Lesur; I.      Botez; D.-H.      Caignard; P.      Lestage; P.      de Tullio

doi:10.2174/092986710792927859

Abstract

Amongst ionotropic glutamatergic receptors, the AMPA receptor subtype has been recognized as a major contributor to the fast excitatory neurotransmission in the central nervous system and the expression and maintenance of longterm potentiation. This receptor subtype also represents an interesting target to develop innovative therapeutic drugs such as positive allosteric modulators (AMPA receptor potentiators) since the enhancement of AMPA signals is expected to be beneficial in the management of several neurological disorders such as depression, schizophrenia, Parkinsons disease and learning-memory deficits linked to Alzheimers disease. This article is dedicated to the use of (hetero)aromatic ring-fused thiadiazines (i.e. benzo- pyrido- and thienothiadiazines) as core structures for the discovery of new positive allosteric modulators of AMPA receptors. Recent advances exploring other chemotypes in the field of AMPA potentiators is the object of a separate review of the present issue.

Keywords: Positive allosteric modulators, AMPA receptor potentiators, benzothiadiazines, pyridothiadiazines, thienothiadiazines, neurological disorders, ionotropic glutamatergic receptors, Alzheimer's disease, schizophrenia, Parkinson's disease, postsynaptic receptors, modulators, thienothiadiazi-nes, central nervous system, Kainic acid