1, 2, 3, 4-tetrahydroacridine-9-amine compound as well as preparation method and application thereof

The technology of an amine compound and tetrahydroacridine, which is applied in the field of medicine, can solve the problems of inability to adapt to the pathological environment and single drug target, and achieve the effect of easy-to-obtain raw materials, simple preparation method, and weaken Aβ neurotoxicity

Active Publication Date: 2021-02-26
NINGBO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these drugs have a single target and cannot adapt to the complex pathological environment of AD

Method used

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  • 1, 2, 3, 4-tetrahydroacridine-9-amine compound as well as preparation method and application thereof
  • 1, 2, 3, 4-tetrahydroacridine-9-amine compound as well as preparation method and application thereof
  • 1, 2, 3, 4-tetrahydroacridine-9-amine compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

specific Embodiment 1

[0048] A novel 1,2,3,4-tetrahydroacridin-9-amine compound, the compound is a compound with the structural formula shown in formula I and II, or a pharmaceutically Acceptable salts, esters or solvates,

[0049]

[0050] Among them, R 1 for H, CH 3 , OCH 3 , OCH 2 CH 3 , Cl, Br, CF 3 , NO 2 , NH 2 Or straight-chain alkanes with carbon number 1-5, R 2 , R 3 for H, n=1, 2, 3, 4 or 5, m=1, 2, 3, 4 or 5, the pharmaceutically acceptable salt, ester or solvate of the compound described in the above formula I and II, wherein the salt is an inorganic acid Salts or organic acid salts; inorganic acid salts are selected from the salts formed by any of the following inorganic acids: hydrochloric acid, sulfuric acid and phosphoric acid; organic acids are selected from the salts formed by any of the following organic acids: acetic acid, trifluoroacetic acid, propane Diacids, citric acid and terephthalic acid.

[0051] The novel 1,2,3,4-tetrahydroacridin-9-amine compounds r...

specific Embodiment 2

[0054] The specific embodiment above is a preparation method of a novel 1,2,3,4-tetrahydroacridin-9-amine compound, comprising the following steps:

[0055] (1) react the compound of formula III and sodium hydroxide in methanol aqueous solution to obtain the compound of formula IV; specifically, at 40°C, dissolve the compound of formula III and sodium hydroxide in an equal volume ratio of 1:1.3 molar ratio React in the mixed aqueous methanol solution for 6 hours to obtain the compound shown in formula IV; thus, it is beneficial to improve the reaction efficiency, reduce side reactions, and increase the yield;

[0056] (2) react the compound of formula IV and the compound of formula V in phosphorus oxychloride to obtain the compound of formula VI; specifically, at 0°C, add the compound shown in formula IV and the compound shown in formula V according to the molar ratio of 1:1.2 In phosphorus oxychloride, transfer to 110 DEG C and react for 6 hours to obtain the compound shown i...

Embodiment 1

[0064] Example 1: Compound 1 preparation of

[0065] 1. Preparation of 2-aminobenzoic acid

[0066] Ethyl 2-aminobenzoate (6.06 mmol) and sodium hydroxide (7.878 mmol) were stirred in methanol (5 mL) and water (5 mL), and the mixture was stirred at 40° C. for 6 hr. After the reaction was completed, methanol was removed by rotary evaporation, and the resulting solution was acidified to pH 3-4 with hydrochloric acid. The resulting suspension was stirred for 10 minutes, the precipitate was filtered and dried to obtain a white solid powder with a yield of 95%. The structural data of the compound was characterized as: 1 H NMR (600MHz, CDCl 3 ):7.69(d, J=7.8,1H),6.93(t,J=7.6,1H),6.45(d,J=8.1,1H),6.37(t,J=6.4,1H),3.17(s, 1H).

[0067] 2. Preparation of 9-chloro-1,2,3,4-tetrahydroacridine

[0068] The intermediate 2-aminobenzoic acid (3.6 mmol) and cyclohexanone (4.32 mmol) obtained in the previous step were added into phosphorus oxychloride (10 mL) at 0°C, and then refluxe...

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Abstract

The invention discloses a 1, 2, 3, 4-tetrahydroacridine-9-amine compound as well as a preparation method and application thereof. The compound is characterized in that: tacrine is taken as a parent nucleus; the compound has structural formulas shown in formulas I and II or pharmaceutically acceptable salts, esters or solvates of the compounds shown in the formulas I and II; and the compound can beused for preparing medicines for resisting Alzheimer's disease, medicines for delaying neurodegenerative diseases, medicines for repairing cholinergic neurons in vitro, medicines for resisting oxidative stress injury in vitro and medicines for relieving beta-amyloid protein (A beta) neurotoxicity, improving cognitive disorder through a CREB-ERK pathway or improving cognitive disorder through reducing Tau protein phosphorylation. Thecompound has the advantage of excellent anti-Alzheimer's disease activity.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to a 1,2,3,4-tetrahydroacridin-9-amine compound, a preparation method thereof and an application in anti-Alzheimer's disease. Background technique [0002] Neurodegenerative diseases are a group of disorders characterized by the progressive loss of neurons in the brain and spinal cord. Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly. At present, there are more than 50 million AD patients in the world. According to the World Health Organization, the number of AD patients in the world will reach 82 million in 2030 and 152 million in 2050. At the same time, AD will become the disease with the second highest mortality after cardiovascular disease. According to the report of the Alzheimer Association, the lifelong care costs of AD patients in 2018 were as high as 350,174 US dollars, which brought a serious economic burden to social families. [0003] The...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/14C07D401/12A61P25/28A61P25/00A61P39/06A61P39/02
CPCA61P25/00A61P25/28A61P39/02A61P39/06C07D401/12C07D401/14
Inventor 章彬崔巍何山张盼盼王宁邹佳美刘志文
Owner NINGBO UNIV
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