Tetramethylpyrazine substituted p-hydroxybenzyl alcohol analog derivative (LQC-F) having neuroprotection activity, and applications thereof

A technology for p-hydroxybenzyl alcohol and derivatives is applied in the field of ligustrazine derivatives and their preparation, which can solve the problems of unclear components of traditional Chinese medicine compounds, insufficient understanding of the mechanism of action, and limited clinical application.

Inactive Publication Date: 2018-08-28
雷鹏程
View PDF6 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Traditional Chinese medicine compound has significant advantages in the treatment of the above chronic and complex diseases, but due to problems such as unclear ingredients and insufficient understanding of the mechanism of action of traditional Chinese medicine compound, its clinical application has been greatly limited

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Tetramethylpyrazine substituted p-hydroxybenzyl alcohol analog derivative (LQC-F) having neuroprotection activity, and applications thereof
  • Tetramethylpyrazine substituted p-hydroxybenzyl alcohol analog derivative (LQC-F) having neuroprotection activity, and applications thereof
  • Tetramethylpyrazine substituted p-hydroxybenzyl alcohol analog derivative (LQC-F) having neuroprotection activity, and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] (4-((3,5,6-trimethylpyrazin-2-yl)methoxy)phenyl)methanol(1a)

[0056] Add 260mg (2.1mmol) 4-hydroxybenzyl alcohol, 358mg (2.1mmol) TMP-Cl, 290mg (2.1mmol) potassium carbonate to the round bottom bottle successively; ℃ reaction 4h. TLC [V (petroleum ether): V (acetone) = 2: 1] detected that the reaction was almost complete, cooled and filtered. Add 5-10 times the amount of saturated sodium carbonate aqueous solution to the filtrate to disperse, extract 3-4 times with an equal amount of ethyl acetate, combine the ethyl acetate layers, and wash with saturated aqueous sodium chloride until neutral (a small amount of multiple times), without Dry over sodium sulfate, filter, and evaporate to dryness under reduced pressure. The residue was separated on a silica gel column to obtain 437.23 mg of a white solid. M.P.: 92.1-92.6°C, yield 80.7%.

[0057] 1 H-NMR (500MHz, CDCl 3 ) (ppm): 7.27 (d, j = 8.3Hz, 2H, Ar-H), 6.97 (d, j = 8.3Hz, 2H, Ar-H), 5.12 (s, 2H, -C H 2 ), 4.6...

Embodiment 2

[0059] 2-(4-((3,5,6-trimethylpyrazin-2-yl)methoxy)phenyl)ethanol (1b).

[0060] Add 276mg (2.0mmol) p-hydroxyphenylethanol, 341mg (2.0mmol) TMP-Cl, 276mg (2.0mmol) potassium carbonate in turn to the round bottom bottle; then add 20mL N,N-dimethylformamide, under nitrogen protection, 85°C Reaction 4h. TLC [V (petroleum ether): V (acetone) = 2: 1] detected that the reaction was almost complete, cooled and filtered. Add 5-10 times the amount of saturated sodium carbonate aqueous solution to the filtrate to disperse, extract 3-4 times with an equal amount of ethyl acetate, combine the ethyl acetate layers, and wash with saturated aqueous sodium chloride until neutral (a small amount of multiple times), without Dry over sodium sulfate, filter, and evaporate to dryness under reduced pressure. The residue was separated on a silica gel column to obtain 357.49 mg of a white solid. M.P.: 91.9-92.3°C, yield 65.7%.

[0061] 1 H-NMR (500MHz, CDCl 3 ) (ppm): 7.13 (d, j = 8.3Hz, 2H, Ar...

Embodiment 3

[0063] (3-methoxy-4-((3,5,6-trimethylpyrazin-2-yl)methoxy)phenyl)methanol (1c).

[0064] Add 308mg (2.0mmol) vanillyl alcohol, 341mg (2.0mmol) TMP-Cl, 276mg (2.0mmol) potassium carbonate in turn to the round bottom bottle; then add 20mL N,N-dimethylformamide, and react at 85°C under nitrogen protection 4h. TLC [V (petroleum ether): V (acetone) = 2: 1] detected that the reaction was almost complete, cooled and filtered. Add 5-10 times the amount of saturated sodium carbonate aqueous solution to the filtrate to disperse, extract 3-4 times with an equal amount of ethyl acetate, combine the ethyl acetate layers, wash with saturated aqueous sodium chloride until neutral (a small amount of multiple times), anhydrous Dry over sodium sulfate, filter, and evaporate to dryness under reduced pressure. The residue was separated on a silica gel column to obtain 323.65 mg of a white solid. M.P.: 112.7-113.2°C, yield 56.2%.

[0065] 1 H-NMR (500MHz, CDCl 3 ) (ppm): 6.97 (d, j = 8.0Hz, ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a tetramethylpyrazine substituted p-hydroxybenzyl alcohol analog derivative (LQC-F) having neuroprotection activity, and applications thereof, and provides a class of tetramethylpyrazine substituted p-hydroxybenzyl alcohol analog derivatives having a structure general formula 1, wherein the compound comprises a p-hydroxybenzyl alcohol analog mother nucleus and a substituent containing a tetramethylpyrazine structure, the structure general formula is represented by the formula 1, R1 is any one selected from -OH, -NH2, 3,5,6-trimethyltetramethylpyrazine-2-methyleneoxy, 3,5,6-trimethyltetramethylpyrazine-2-formyloxy and 3,5,6-trimethyltetramethylpyrazine-2-formamide, R2 is any one selected from -H and -OCH3, R3 is any one selected from -OH, 3,5,6-trimethyltetramethylpyrazine-2-methylene and 3,5,6-trimethyltetramethylpyrazine-2-formyl, at least one of R1-R3 is a substituent containing a tetramethylpyrazine structure, and n is 1 or 2. The invention further providesa preparation method of the derivative, and applications of the derivative in preparation of drugs for treatment of brain nerve injury and sequela thereof. The formula 1 is defined in the specification.

Description

technical field [0001] The invention relates to a ligustrazine derivative and its preparation method and application, in particular to a ligustrazine p-hydroxybenzyl alcohol analog derivative, a preparation method and its application in neuroprotection, and belongs to the field of medicinal chemistry. Background technique [0002] At present, brain diseases such as stroke, Alzheimer's disease, Parkinson's disease, and traumatic brain injury seriously endanger human health. The occurrence and development of brain diseases are accompanied by different degrees of nerve cell damage. For example, when ischemic stroke occurs, the decrease in blood flow leads to changes in the function of normal cells, and the brain tissue is very sensitive to local ischemia. Even brief ischemia of neurons triggers a cascade of events that culminates in neuronal death. Therefore, neuroprotective agents are widely used as an important therapeutic drug in the first-line clinical treatment of the abo...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/12C07D241/24A61K31/4965A61K31/497A61P25/00A61P25/28A61P25/16
CPCC07D241/12C07D241/24
Inventor 张晨泽王鹏龙雷鹏程
Owner 雷鹏程
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap