Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard St. Louis, MO, 63110, USA.
Molecules. 2021 Feb 24;26(5):1202. doi: 10.3390/molecules26051202.
The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots and stroke, to bixafen, a pyrazole-carboxamide fungicide used to control diseases of rapeseed and cereal plants, has encouraged both medicinal and organic chemists to explore new methods in developing pyrazole-containing compounds for different applications. Although numerous synthetic strategies have been developed in the last 10 years, there has not been a comprehensive overview of synthesis and the implication of recent advances for treating neurodegenerative disease. This review first presents the advances in pyrazole scaffold synthesis and their functionalization that have been published during the last decade (2011-2020). We then narrow the focus to the application of these strategies in the development of therapeutics for neurodegenerative diseases, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD).
吡唑骨架在各种具有生物活性的分子中广泛存在,从抗凝剂阿哌沙班(用于治疗和预防血栓形成和中风)到吡唑-羧酰胺类杀菌剂双苯氟嗪(用于控制油菜和谷类作物的病害),这一现象引起了药物和有机化学家的兴趣,他们都在探索开发用于不同应用的含吡唑化合物的新方法。尽管在过去的 10 年中已经开发了许多合成策略,但对于治疗神经退行性疾病,并没有一个全面的合成综述和对最新进展的影响。本文首先介绍了过去十年(2011-2020 年)发表的吡唑骨架合成及其功能化方面的进展。然后,我们将重点缩小到这些策略在神经退行性疾病治疗药物开发中的应用,特别是针对阿尔茨海默病(AD)和帕金森病(PD)。