Drug Research Center (Centre Interfacultaire de Recherche du Médicament-CIRM), Université de Liège, Liège, Belgium.
Curr Med Chem. 2010;17(30):3575-82. doi: 10.2174/092986710792927859.
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.
在离子型谷氨酸能受体中，AMPA 受体亚型已被认为是中枢神经系统中快速兴奋性神经传递的主要贡献者，也是长时程增强的表达和维持的主要贡献者。由于增强 AMPA 信号有望有益于管理几种神经障碍，如抑郁症、精神分裂症、帕金森病和与阿尔茨海默病相关的学习记忆缺陷，因此该受体亚型也代表了开发创新治疗药物（如正变构调节剂（AMPA 受体激动剂）的一个有趣目标。本文致力于使用（杂）芳环稠合噻二嗪（即苯并吡啶并噻二嗪）作为发现新型 AMPA 受体正变构调节剂的核心结构。目前这一期的另一篇综述探讨了该领域中其他化学型的最新进展。
