New Tacrines as Anti-Alzheimer`s Disease Agents. II. The (Benzo)ChromenoPyranoTacrines.

New Tacrines as Anti-Alzheimer`s Disease Agents. II. The (Benzo)ChromenoPyranoTacrines.

Curr Top Med Chem. 2018 Jan 12;:

Authors: Oset-Gasque MJ, Marco-Contelles J

Abstract
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 Nowadays, this agent has been withdrawn from the clinics due to secondary effects, among them, and the most important, its hepatotoxicity.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, in our laboratory, in the last years we have prepared a new heterocyclic tacrines by changing the benzene ring present in tacrine by appropriate heterocyclic motifs. Based on this approach, in this review we will summarize the results that we have found in the ChromenoPyranoTacrines, one of the family of tacrine analogues, highlighting their pharmacological profile, such as their cholinesterase inhibition power, calcium channel blockade, antioxidant capacity, Ab-amyloid inhibition aggregation capacity, and neuroprotection. As a result of this work we have identified permeable, neuroprotective MTD tacrines devoid of toxic effects, showing potent anti-cholesterasic properties, 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) that deserve attention and further development looking for new, and more efficient drugs for AD therapy.

PMID: 29332585 [PubMed - as supplied by publisher]

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