Design, Synthesis, Evaluation Of Indanone Derivatives For Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative syndrome that leads to memory loss and decline in cognitive function. This is one of the leading causes of dementia and currently has no single known cause. Loss of cholinergic neurons, formation of amyloid-β (Aβ) aggregates, oxidative stress and changes in the activity of monoamine oxidase (MAO) are all thought to be involved in the development of the disease and are the targets for most current therapeutic approaches. Most of this only aim at one single target and thus have only limited success in relieving symptoms in patients with AD. The indanone ring is the active pharmaceutical ingredient of the most prescribed cholinesterase inhibitor donepezil. This ring has formed the basis of many strategies for the development of anti-AD drugs. This review follows the design, synthesis, in vitro and in vivo testing and structure activity relationships of numerous series of indanone derivatives. Published series have shown sub-nanomolar inhibitory activity against AChE or MAO-B and in some cases against Aβ aggregation as well. However, so far only a few of these compounds have been tested in vivo and the available data regarding their pharmacokinetic and pharmacological profile is very limited.