2'-Hydroxyl-3phenyl propiophenone compound and preparation method and application thereof

Abstract

The invention relates to a 2'-hydroxyl-3phenyl propiophenone compound and a preparation method and application thereof. The preparation method comprises the following steps that 1, 3-hydroxybenzaldehyde is used as an initial raw material, and under a first solvent and a first alkaline condition, the 3-hydroxybenzaldehyde reacts with dibromide to obtain bromine alkoxy benzaldehyde; 2, the bromine alkoxy benzaldehyde reacts with secondary amine under a second solvent and a second alkaline condition to obtain amine alkoxy benzaldehyde; 3, the amine alkoxy benzaldehyde and 2-hydroxyacetophenone react under a third solvent and a third alkaline condition to obtain amine alkoxy chalcone; 4, Pd / C is added to the amine alkoxy chalcone, and under the hydrogen atmosphere, under the condition of a fourth solvent, catalytic hydrogenation is conducted to obtain the 2'-hydroxyl-3phenyl propiophenone compound. The compound has obvious selective butyrycholine enzyme inhibition activity and can be applied to treatment and / or prevention of related neurodegeneration 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...

AI Technical Summary

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

Images