Alzheimer’s disease (AD) is one of the most common forms of dementia among elder people, which is a progressive neurodegenerative disease that results from a chronic loss of cognitive activities. It has been observed that AD is multifactorial, hence diverse pharmacological targets that could be followed for the treatment of AD. The Food and Drug Administration has approved two types of medications for AD treatment such as cholinesterase inhibitors (ChEIs) and N-methyl-d-aspartic acid receptor (NMDAR) antagonists. Rivastigmine, donepezil, and galantamine are the ChEIs that have been approved to treat AD. On the other hand, memantine is the only non-competitive NMDAR antagonist approved in AD treatment. As compared with placebo, it has been revealed through clinical studies that many single-target therapies are unsuccessful to treat multifactorial Alzheimer’s symptoms or disease progression. Therefore, due to the complex nature of AD pathophysiology, diverse pharmacological targets can be hunted. In this article, based on the entwined link of acetylcholinesterase (AChE) and NMDAR, we represent several multifunctional compounds in the rational design of new potential AD medications. This review focus on the significance of privileged scaffolds in the generation of the multi-target lead compound for treating AD, investigating the idea and challenges of multi-target drug design. Furthermore, the most auspicious elementary units for designing as well as synthesizing hybrid drugs are demonstrated as pharmacological probes in the rational design of new potential AD therapeutics.

阿尔茨海默病 (AD) 是老年人中最常见的痴呆症之一，它是一种进行性神经退行性疾病，由认知活动的慢性丧失引起。已经观察到 AD 是多因素的，因此可以遵循多种药理学目标来治疗 AD。美国食品和药物管理局已批准两种类型的 AD 治疗药物，例如胆碱酯酶抑制剂 (ChEIs) 和N-甲基-d-天冬氨酸受体 (NMDAR) 拮抗剂。卡巴拉汀、多奈哌齐和加兰他敏是已被批准用于治疗 AD 的 CheIs。另一方面，美金刚是唯一被批准用于 AD 治疗的非竞争性 NMDAR 拮抗剂。与安慰剂相比，临床研究表明，许多单靶点疗法无法成功治疗多因素阿尔茨海默氏症的症状或疾病进展。因此，由于 AD 病理生理学的复杂性，可以寻找不同的药理学靶点。在本文中，基于乙酰胆碱酯酶 (AChE) 和 NMDAR 的交织联系，我们在新的潜在 AD 药物的合理设计中代表了几种多功能化合物。本综述重点关注特权支架在产生治疗 AD 的多靶点先导化合物中的重要性，研究多靶点药物设计的想法和挑战。此外，用于设计和合成混合药物的最吉祥的基本单元被证明是合理设计新的潜在 AD 疗法的药理学探针。