LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.
Eur J Med Chem. 2021 Mar 15;214:113209. doi: 10.1016/j.ejmech.2021.113209. Epub 2021 Jan 25.
Alzheimer's disease (AD) is one of the most common types of dementia, especially in elderly, with an increasing number of people suffering from this disease worldwide. There are no available disease-modifying therapies and only four drugs are approved for the relief of symptoms. Currently, the therapeutic approach used for AD treatment is based on single target drugs, which are not capable to stop its progression. To address this issue, multi-target compounds, combining two or more pharmacophores in a single molecular entity, have gained increasing interest to deal with the multiple factors related to AD. The exact cause of AD is not yet completely disclosed, and several hallmarks have been associated to this neurodegenerative disease. Even though, the accumulation of both amyloid-β plaques (Aβ) and neurofibrillary tangles (NFTs) are fully accepted as the main AD hallmarks, being object of lots of research for early-stage diagnosis and pharmacological therapy. In this context, this review summarizes the state-of-the-art in the field of dual-target inhibitors of both Aβ and tau aggregation simultaneously, including the design and synthetic strategy of the dual-target compounds, as well as a brief structure-activity relationships (SAR) analysis.
阿尔茨海默病（AD）是最常见的痴呆症类型之一，尤其是在老年人中，全球范围内越来越多的人患有这种疾病。目前尚无可行的疾病修饰疗法，仅有四种药物被批准用于缓解症状。目前，AD 治疗的治疗方法基于单靶点药物，这些药物无法阻止其进展。为了解决这个问题，结合了两种或多种药效团的多靶点化合物，即单一分子实体中的两种或多种药效团，已引起越来越多的关注，以应对与 AD 相关的多种因素。AD 的确切病因尚未完全揭示，有几个特征已与这种神经退行性疾病相关联。尽管如此，淀粉样β斑块（Aβ）和神经原纤维缠结（NFTs）的积累被完全认为是 AD 的主要特征，成为早期诊断和药物治疗的大量研究对象。在这种情况下，本文综述了同时抑制 Aβ和 tau 聚集的双靶点抑制剂的最新研究进展，包括双靶点化合物的设计和合成策略，以及简要的构效关系（SAR）分析。
