Preparation method of E-3,4-dihydroxyphenylvinyl ketone and application thereof as nerve protection drug

The technology of a dihydroxyphenyl and compound is applied in the preparation of E-3,4-dihydroxystyryl ketone compounds and its application field as a neuroprotective drug, which can solve the problem of difficulty in permeating the blood-brain barrier, metabolic rate wait for the question

Inactive Publication Date: 2014-07-23
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In view of the shortcomings of caffeic acid phenethyl ester that is not easy to pass through the blood-brain barrier and has a fast metabolism in the body, we modified its structure to make the new compound easier to pass through the blood-brain barrier and have stronger stability, thereby improving neuroprotective activity

Method used

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  • Preparation method of E-3,4-dihydroxyphenylvinyl ketone and application thereof as nerve protection drug
  • Preparation method of E-3,4-dihydroxyphenylvinyl ketone and application thereof as nerve protection drug
  • Preparation method of E-3,4-dihydroxyphenylvinyl ketone and application thereof as nerve protection drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Preparation of 1-phenylbut-1-en-3-one (compound 1a)

[0029] After adding 5ml of acetone to 5ml of 10% NaOH aqueous solution, slowly add benzaldehyde (5.30g, 0.05mol) in acetone solution (10ml) dropwise, control the reaction temperature not to exceed 30°C, drop it for about 1h, continue the reaction for 3h, and detect by TLC The response is complete. The reaction solution was neutralized to PH=7 with 10% HCl, the solvent was spin-dried under reduced pressure, extracted with ethyl acetate, the ester layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was spin-dried under reduced pressure, separated and purified by silica gel column (eluted with petroleum ether / ethyl acetate) to obtain the target compound 1a, 6.0 g of light yellow crystals, and the yield was 82.5%. m.p.39-41°C. 1 HNMR (400MHz, CDCl 3 )δ: 7.46 (d, .J=16.2Hz, 1H, C2-H), 7.14-7.30 (m, 5H, Ar-H), 6.61 (d, J=16.2Hz, 1H, C1-H), 2.30 (s, 3H, CH 3 )

[003...

Embodiment 2

[0043] Preparation of 4-phenylbutan-2-one (compound 2a)

[0044] Dissolve 1a (0.29g, 2.0mmol) in dichloromethane (10ml), add 10% Pb / C (30mg), react in hydrogen atmosphere for 12h, TLC detects that the reaction is complete, filter with celite, and decompress the filtrate After spin-drying, separation and purification on a silica gel column (elution with petroleum ether / ethyl acetate) gave the target compound 2a as a colorless liquid with a yield of 90.0%.

[0045] Preparation of 4-(3-chlorophenyl)-butan-2-one (2b)

[0046] Using the synthesis method of compound 2a above, 2b was obtained by using 1-(3-chlorophenyl)-but-1-en-3-one as a reactant with a yield of 89.3%.

[0047] Preparation of 4-(3,4-dihydroxyphenyl)-butan-2-one (2c)

[0048] Using the synthesis method of compound 2a above, 2c was obtained by using 1-(3,4-dihydroxyphenyl)-but-1-en-3-one as a reactant, with a yield of 85.7%, m.p.85-86°C.

[0049] Preparation of 4-(3-methoxy-4-hydroxyphenyl)-butan-2-one (2d)

[00...

Embodiment 3

[0058] Preparation of E-1-(3,4-dihydroxyphenyl)-5-phenyl-pent-1-en-3-one (3a)

[0059] Add 4-phenylbutan-2-one (0.45g, 3mmol) and a catalytic amount of pyrrolidine and acetic acid into tetrahydrofuran (30ml) solvent and stir, slowly add 3,4-dihydroxybenzaldehyde (0.38g, 3mmol) of tetrahydrofuran (20ml) solution, drop it for 1h, stir the reaction at room temperature in the dark, TLC detects that the reaction is complete, spin down the solvent under reduced pressure, add a small amount of water, extract with ethyl acetate, combine the ester layers, and wash with saturated saline Wash with saturated sodium bisulfite solution, dry over anhydrous sodium sulfate, spin dry the solvent under reduced pressure, separate and purify with silica gel column (petroleum ether / ethyl acetate elution) to obtain the target compound 3a as a yellow solid, 0.37g, yield 55.5% , m.p.153-155°C. 1 HNMR (400MHz, DMSO-d 6 )δ: 9.37(s, 2H, 2×OH), 7.49(d, J=16.2Hz, 1H, C2-H), 6.75-7.84(m, 8H, Ar-H), 6.53(d...

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Abstract

The invention relates to a E-3,4-dihydroxyphenylvinyl ketone compound I having a formula represented in the description and an application thereof in preparation of nerve protection drugs or drug compositions for treating neurodegenerative diseases; wherein definitions of each group in the formula are listed in the description. The invention also relates to a preparation method of the compound.

Description

technical field [0001] This patent relates to the use of E-3,4-dihydroxystyryl ketone compounds in the preparation of neuroprotective drugs for neurodegenerative diseases, and also relates to the preparation methods of such compounds. Background technique [0002] Neurodegenerative diseases are a class of chronic, progressive neurological diseases. Such diseases mainly include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, cerebellar atrophy, different types of spinocerebellar ataxia, spinal muscular atrophy , Primary lateral sclerosis, etc. In recent years, the number of neurodegenerative diseases has been increasing. For example, the prevalence of Alzheimer's disease in my country reaches 2% to 5%, and the annual new incidence reaches 1%. Studies have found that neurodegenerative diseases are caused by many different reasons, including insufficient nutrition provided by neurons or glial cells, hyperactiv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C49/248C07C49/255C07C45/74C07C45/61C07C69/16C07C67/035A61K31/12A61K31/222A61P25/28A61P25/16A61P25/00A61P9/10
CPCY02P20/55C07C49/248C07C45/61C07C45/74C07C49/255C07C67/035C07C69/16
Inventor 刘俊义宁显玲张志丽郭莹王孝伟田超
Owner PEKING UNIV
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