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Salicylamide derivative crystal

A technology of compounds and diffraction peaks, applied in the field of crystallization of salicylic acid amide derivatives

Active Publication Date: 2014-02-19
SHENZHEN WANHE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It has also been reported that NF-κB affects CXCR 4 expression (Helbig et al., 2003), suggesting that NF-κB inhibitors may be equally effective against X4-tropic isolates that arise during late stages of infection

Method used

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  • Salicylamide derivative crystal
  • Salicylamide derivative crystal
  • Salicylamide derivative crystal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Example 1: Preparation of compound of formula 1 (5,6-epoxy-4-hydroxyl-3-salicyylamino-2-cyclohexenone, DHM2EQ) crystallization

[0084] Step 1: Synthesis of N-(2-acetoxybenzoyl)-2,5-dimethoxyaniline

[0085]

[0086] 2,5-Dimethoxyaniline (10.0 g, 65.3 mmol) was dissolved in pyridine (100 ml). Under ice-cooling, a solution of O-acetylsalicyloyl chloride (13.0 g, 65.3 mmol) in ethyl acetate (50 ml) was added thereto over 15 minutes, followed by stirring at the same temperature for 15 minutes. After adding water (10ml) to the reaction solution to stop the reaction, add ethyl acetate (500ml), then successively add 3 equivalents of hydrochloric acid (500ml), water (500ml), 2% aqueous sodium bicarbonate (500ml) and water (500ml )washing. The ethyl acetate layer was dried over Glauber's salt, concentrated under reduced pressure and dried in vacuo to obtain the title compound (19.8 g) as a pale yellow syrup. The compound was used directly in the following step witho...

Embodiment 2

[0111] Embodiment 2: preparation formula 1 compound crystallization

[0112] Under heating conditions (40 DEG C), 5g of the product obtained in step 5 of the above embodiment 1 is dissolved in DMF (5 times its weight is the weight of the compound of formula 1), and absolute ethanol (for example, its volume is 5 times that of the compound of formula 1) is added in this solution. 4 times) and glacial acetic acid (the weight of which is 0.3 times that of the compound of formula 1), cooling and crystallization, filtering out the precipitate, washing with absolute ethanol, and vacuum drying to obtain. The crystallization yield was 83.8%.

[0113] The content is 99.7% (HPLC), of which the total impurity is 0.185%, and the largest single impurity is 0.018%.

[0114] Determination of powder X-ray diffraction, the results are basically the same as figure 1 Consistent, specifically: with figure 1 The 2θ values ​​of the 19 peaks in the figure 1 The 2θ values ​​of the corresponding ...

Embodiment 3

[0116] Embodiment 3: preparation formula 1 compound crystallization

[0117] Under heating conditions (80 DEG C), 5 g of the product obtained in step 5 of the above embodiment 1 is dissolved in DMF (2 times the weight of the compound of formula 1), and absolute ethanol (for example, its volume is DMF) is added to the solution. 8 times) and glacial acetic acid (its weight is 0.1 times that of the compound of formula 1), cooling and crystallization, filtering out the precipitate, washing with absolute ethanol, and vacuum drying to obtain. The crystallization yield was 85.7%.

[0118] The content is 99.9% (HPLC), of which the total impurity is 0.202%, and the largest single impurity is 0.014%.

[0119] Determination of powder X-ray diffraction, the results are basically the same as figure 1 Consistent, specifically: with figure 1 The 2θ values ​​of the 19 peaks in the figure 1 The 2θ values ​​of the corresponding peaks all differ within ±0.10°.

[0120] A total of four dif...

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Abstract

The invention discloses a salicylamide derivative crystal and specifically discloses a compound shown in the formula 1. Under Cu-K alpha radiation, in the powder x-ray diffraction pattern represented by 2 theta angle, the compound has a diffraction peak at about 9.4 degrees. The invention also discloses a preparation method of the compound shown in the formula 1, a pharmaceutical composition containing the compound, and a use of the compound or its pharmaceutically acceptable salts, solvates, esters, prodrugs and isomers in preparation of drugs for treating or preventing cancers, inflammation, autoimmune disease, diabetes, diabetic complication, infection, cardiovascular diseases and ischemia-reperfusion injuries. The compound shown in the formula 1 has good drug properties.

Description

technical field [0001] The present invention relates to the crystallization of salicylic acid amide derivative shown in formula 1, and its preparation method. The crystalline salicylic acid amide derivative can be used for the treatment of cancer, inflammation, autoimmune disease, diabetes and diabetic complications, infection, cardiovascular disease and defective reperfusion injury. Background technique [0002] NF-κB (Nuclear factor-kappa B) activation is involved in various diseases including cancer, diabetes, cardiovascular disease, autoimmune disease, viral replication, septic shock, neurodegenerative disease, ataxia telangiectasia arthritis (AT), arthritis, asthma, inflammatory bowel disease, and other inflammatory conditions. For example, activation of NF-κB by gram-negative bacterial lipopolysaccharide (LPS) can produce septic shock because NF-κB hyperactivates the transcription of many cytokines and modifying enzymes, whose prolonged expression can adversely affect...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D303/36A61K31/625A61P35/00A61P29/00A61P3/10A61P9/00A61P9/10A61P37/00A61P31/00
CPCC07D303/36
Inventor 马俊余卫麟
Owner SHENZHEN WANHE PHARMA
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