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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

New Tacrines as Anti-Alzheimer's Disease Agents. The (Benzo)Chromeno- PyranoTacrines

Author(s): Maria Jesus Oset-Gasque* and Jose Marco-Contelles*

Volume 17 , Issue 31 , 2017

Page: [3349 - 3360] Pages: 12

DOI: 10.2174/1568026618666180112155928

Price: $65


Tacrine was the first drug approved by FDA (US) for the treatment of Alzheimer's disease suffering patients. Nowadays, this agent has been withdrawn from the clinics due to secondary effects, which, most importantly, include hepatotoxicity. However, the research on new tacrine analogues devoid of these therapeutically undesirable effects, but benefiting of their high and well known positive cholinergic power, has produced a number of new non-hepatotoxic tacrines. In this context, our laboratory has recently prepared a new set of heterocyclic tacrines by changing the benzene ring present in tacrine by appropriate heterocyclic motifs. Based on this approach, in this review we summarize the results that we have found in the ChromenoPyranoTacrines, one of the families of tacrine analogues. This highlights their pharmacological profile, such as their cholinesterase inhibition power, calcium channel blockade, antioxidant capacity, Aβ-anti-aggregating, and neuroprotective properties. As a result of this work we have identified permeable, neuroprotective MTD tacrines racemic hit-tacrines 11-amino-12-(3,4,5-trimethoxyphenyl)-7,9,10,12-tetrahydro-8H-chromeno[2,3- b]quinolin-3-ol (6g) and 14-(3,4-dimethoxyphenyl)-9,11,12,14-tetrahydro-10H-benzo[5,6] chromeno [2,3-b] quinolin-13-amine (7i),devoid of toxic effects and showing potent anti-cholinesterasic properties, that deserve attention and further development in order to find new, and more efficient drugs, for AD therapy.

Keywords: Tacrine, ChromenoPyranoTacrines, Multi-Target-Directed (MTD) Ligands, Alzheimer's disease, Aβ-amyloid, Reactive oxygen species.

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