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

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

Volume: 17 Issue: 31

Author(s): Alejandro Romero and Jose Marco-Contelles*

Affiliation:

• Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Juan de la Cierva 3, 28006- Madrid,Spain

Keywords: Tacrine, Pyranotacrines, Acetylcholinesterase inhibitors, Butyrylcholinesterase inhibitors, Alzheimer's disease, Neuroprotection, Multi-Target-Directed Ligands.

Abstract: Tacrine 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 Unfortunately, many treated patients displayed related hepatotoxicity, and hence this drug was withdrawn.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.

Cite this article as:

Romero Alejandro and Marco-Contelles Jose*, Recent Developments on Multi-Target-Directed Tacrines for Alzheimer's Disease. I. The Pyranotacrines, Current Topics in Medicinal Chemistry 2017; 17 (31) . https://dx.doi.org/10.2174/1568026618666180112155639