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

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

Document Type: Research Article

Affiliations: Drug Research Center (Centre Interfacultaire de Recherche du Medicament - CIRM), Laboratoire deChimie Pharmaceutique, Universite de Liege, Avenue de l'Hopital, B-4000 Liege, Belgium.

Publication date: 2010-10-01

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