Abstract：
As a \"silent threat,\" Alzheimer\'s disease (AD) is quickly rising to the top of the list of costly and troublesome diseases facing humanity. It is growing to be one of the most troublesome and expensive conditions, with annual health care costs higher than those of cancer and comparable to those of cardiovascular disorders. One of the main pathogenic characteristics of AD is the deficiency of the neurotransmitter acetylcholine (ACh) which plays a vital role in memory, learning, and attention. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in hydrolyzing ACh. Consequently, a frequent therapy approach for AD is the suppression of AChE and BChE to improve cholinergic neurotransmission and reduce cognitive symptoms. The accumulation of amyloid plaques (Aβ) is a primary factor contributing to neurodegenerative diseases, particularly AD. Glycogen synthase kinase-3β (GSK3-β) is regarded as a pivotal player in the pathophysiology of AD since dysregulation of this kinase affects all major hallmarks of the disease, such as tau phosphorylation, Aβ aggregation, memory, neurogenesis, and synaptic function. One of the most challenging and risky issues in modern medicinal chemistry is the urgent and ongoing need for the study and development of effective therapeutic candidates for the treatment of AD. A significant class of heterocyclic molecules that can target the complex and multifactorial pathogenesis of AD are fused thiophene derivatives. The goal of the current review is to demonstrate the advancements made in fused thiophene derivatives\' anti-AD activity. It also covers their mechanisms of action and studies of the structure-activity relationships in addition to the compilation of significant synthetic routes for fused thiophene derivatives with anti-AD potential. This review is intended to stimulate new ideas in the search for more rationale designs of derivatives based on fused thiophene, hoping to be more potent in treating AD.
摘要：
作为一个“无声的威胁”，“阿尔茨海默病（AD）正在迅速上升到人类面临的昂贵和麻烦的疾病列表的顶部。它正在成长为最麻烦和最昂贵的条件之一，每年的医疗保健费用高于癌症，与心血管疾病相当。AD的主要致病特征之一是神经递质乙酰胆碱（ACh）的缺乏，在记忆中起着至关重要的作用，学习,和注意。乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）在水解ACh中起着至关重要的作用。因此,AD的常用治疗方法是抑制AChE和BChE以改善胆碱能神经传递并减轻认知症状。淀粉样斑块（Aβ）的积累是导致神经退行性疾病的主要因素，尤其是AD。糖原合成酶激酶-3β（GSK3-β）被认为是AD病理生理学中的关键角色，因为该激酶的失调会影响该疾病的所有主要标志。比如tau磷酸化，Aβ聚集，记忆,神经发生，和突触功能。现代药物化学中最具挑战性和风险的问题之一是迫切需要研究和开发用于治疗AD的有效治疗候选物。可以靶向AD的复杂和多因素发病机理的一类重要的杂环分子是稠合噻吩衍生物。本综述的目的是证明稠合噻吩衍生物抗AD活性的进展。除了汇编具有抗AD潜力的稠合噻吩衍生物的重要合成路线外，它还涵盖了它们的作用机制和结构-活性关系的研究。这篇评论旨在激发新的想法，以寻找基于稠合噻吩的衍生物的更多理论设计，希望在治疗AD方面更有效。
