Amine alkoxy chalcone compound and preparation method and application thereof

Abstract

The invention discloses an amine alkoxy chalcone compound, and a preparation method and application thereof. The preparation method comprises the following steps: (1) 3-hydroxybenzaldehyde is used as a starting material and reacts with a dibromide compound under a first solvent and a first alkaline condition to obtain bromoalkoxybenzaldehyde; (2) the bromoalkoxybenzaldehyde reacts with secondary amine in a second solvent under a second alkaline condition to obtain amine alkoxy benzaldehyde; and (3) the amine alkoxy benzaldehyde and 2-hydroxyacetophenone are subjected to a third solvent and a third alkaline condition to obtain the target compound, i.e. amine alkoxy chalcone compound. The amine alkoxy chalcone compound has selective butyrylcholinesterase inhibitory activity, selective monoamine oxidase B inhibitory activity, selective metal ion chelating activity and Abeta aggregation inhibitory activity in vitro, and can be used for treating and / or preventing neurodegenerative related diseases.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to an amine alkoxychalcone compound, a preparation method and application thereof. Background technique [0002] Alzheimer's disease (AD) is one of the diseases with the highest morbidity and mortality among the elderly. According to the "2015 Global Alzheimer's Report" released by Alzheimer's Disease International (ADI), more than 46 million people in the world suffered from dementia in 2015. It is predicted that by 2050, the world's There will be 131.5 million people suffering from dementia, and the incidence rate of dementia patients in China has reached 6.61%. With the prolongation of the average life expectancy, the disease has developed into a major burden on the society and the medical care system, and has brought heavy mental and economic pressure to the society, patients and their families. The drugs currently approved by the FDA are mainly acetylcholinesterase inhibito...

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Problems solved by technology

In previous reports, scutellarin aglycon carbamate derivatives (CN10337956A, CN102603698A), stilbene or ethane carbamate compounds (CN102816090A), and isoflavone carbamate compounds (CN102827131A) were discovered. Ferulic acid carbamate compounds (CN105837497A, CA105601540A, CN105646289A), although these compounds have better acetylcholinesterase inhibitory activity and antioxidant activity, and have a little inhibitory effect to Aβ aggregation, simultaneously to butyrylcholinesterase Enzyme inhibitory activity is very poor, resulting in suboptimal efficacy of these compounds for the treatment of AD in animal models

Chinese patents CN105439876B, CN105481706B, and CN105481796B also disclose some chalcone compounds, which have good acetylcholinesterase inhibitory activity, general inhibitory activity to butyrylcholinesterase, and selective inhibition to acetylcholinesterase These drugs can only partially relieve the symptoms of AD patients in the short term, and cannot effectively prevent or reverse the progress of the disease. Cholinergic side effects

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