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Recent Developments on Multi-Target-Directed Tacrines for Alzheimer's Disease. I. The Pyranotacrines

AutorRomero, Alejandro ; Marco-Contelles, José
Palabras claveMulti-Target-Directed Ligands
Alzheimer’s disease
Butyrylcholinesterase inhibitors
Acetylcholinesterase inhibitors
Fecha de publicación2017
EditorBentham Science Publishers
CitaciónCurrent Topics in Medicinal Chemistry 17: 3328-3335 (2017)
ResumenTacrine was the first drug to display beneficial effects on cognitive impairment of Alzheimer Disease (AD) patients. Unfortunately, many treated patients displayed related hepatotoxicity, and hence this drug was withdrawn. Notwithstanding, recent efforts have been directed to design small tacrine analogues targeting the underlying pathogenic mechanisms of AD. In this context, we have developed a number of pyranotacrines by changing the benzene fused ring in tacrine by a 4Hpyran. Based on this strategy, in this account we will show the tacrine analogues that we have designed, synthesized and evaluated as potential multipotent agents for AD in the last years. We have demonstrated that this approach is possible, and that a number of readily available tacrine analogues show cholinesterase inhibition power, as well as other pharmacological properties, such as calcium channel blockade, antioxidant properties, neuroprotection, Aβ-amyloid inhibition aggregation capacity, etc., making them suitable multipotent molecules for further development for the potential treatment of AD.
Versión del editorhttp://dx.doi.org/10.2174/1568026618666180112155639
Identificadoresdoi: 10.2174/1568026618666180112155639
issn: 1568-0266
e-issn: 1873-4294
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