A kind of 2'-hydroxyl-3 phenyl propiophenone compound and its preparation method and application

Abstract

A kind of 2'-hydroxyl-3 phenylpropiophenone compound of the present invention and its preparation method and application, preparation method comprises the following steps: (1) take 3-hydroxybenzaldehyde as starting raw material, in the first solvent and the first alkali Under neutral conditions, react with dibromide to obtain bromoalkoxybenzaldehyde; (2) bromoalkoxybenzaldehyde reacts with secondary amine under the second solvent and the second basic condition to obtain amine alkoxybenzaldehyde (3) amine alkoxy benzaldehyde and 2-hydroxyacetophenone under the third solvent and the third basic condition, obtain amine alkoxy chalcone; (4) add in the amine alkoxy chalcone Pd / C, under a hydrogen atmosphere, under the fourth solvent condition, catalytic hydrogenation to obtain 2'-hydroxyl-3 phenylpropiophenone compound. The compound of the present invention has significant selective butyrylcholinease inhibitory activity 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, and in particular relates to a 2'-hydroxyl-3-phenylpropiophenone compound and its preparation method and application. 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 acetylch...

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Problems solved by technology

[0005] Patent literature discloses scutellarin aglycone carbamate derivatives (CN10337956A, CN102603698A), stilbene or ethane carbamate compounds (CN102816090A), isoflavone carbamate compounds (CN102827131A), ferulic acid Carbamate compounds (CN105837497A, CA105601540A, CN105646289A), chalcone compounds (CN105439876B, CN105481706B, CN105481796B), although these compounds have good acetylcholinesterase inhibitory activity and antioxidant activity, but for butyrylcholinesterase The inhibitory activity of the enzyme is very poor, and it has a selective inhibitory effect on acetylcholinesterase, which leads to the poor efficacy of these compounds in the treatment of AD in animal models. These drugs can only partially relieve the symptoms of AD patients in the short term, and cannot effectively prevent Or reverse the course of the disease, not suitable for the treatment of moderate to severe Alzheimer's disease, and there are classic cholinergic side effects caused by acetylcholinesterase inhibition

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