Departamento de Química Orgánica and Química Inorgánica. Ctra. Madrid-Barcelona, Universidad de Alcalá, Km. 33, 6, 28871, Madrid, Spain.
Laboratoire de Chimie Organique et Thérapeutique, Neurosciences intégratives et cliniques EA 481, Univ. Bourgogne Franche-Comté, UFR Santé, 19, rue Ambroise Paré, F-25000, Besançon, France.
Chem Rec. 2021 Jan;21(1):162-174. doi: 10.1002/tcr.202000107. Epub 2020 Nov 10.
Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non-hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.
在这里，我们回顾了我们最近在鉴定用于治疗阿尔茨海默病 (AD) 的新型他克林类似物方面的进展。他克林是第一种被批准用于 AD 治疗的胆碱酯酶抑制剂，但它并没有阻止 AD 的进展，仅产生了一些认知改善，但其主要由于其肝毒性而产生了次要作用。因此，该药物已从临床应用中撤出。从那时起，许多出版物都描述了非肝毒性他克林，此外，还通过将其胆碱酯酶抑制谱与调节 AD 相关的其他生物靶标相结合，来设计多靶他克林。
