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Celecoxib derivative and preparation method and application thereof

A technology of celecoxib and derivatives, which is applied in the field of celecoxib derivatives and their preparation, can solve the problems of low absorption and poor dissolution, and achieve good medicinal biological activity

Pending Publication Date: 2019-08-09
ANHUI HEALSTAR PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Celecoxib has a good therapeutic effect on arthritis, but celecoxib is a poorly water-soluble drug, and its dissolution is not good
Only celecoxib capsules are currently on the market, and the absorption in the body is very low

Method used

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  • Celecoxib derivative and preparation method and application thereof
  • Celecoxib derivative and preparation method and application thereof
  • Celecoxib derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1 Compound I 1 preparation of

[0022] 100mL dry three-necked flask, install stirrer, thermometer, add celecoxide (95g, 0.249mol) and dry anhydrous acetonitrile 570mL and potassium carbonate (36g, 0.26mol) to wherein, stir; Slowly add the methanesulfonic acid to 30g The acetonitrile solution of acid chloride (60mL, 0.262mmol) was heated to 75-80°C and reacted for 8h, and the end point of the reaction was identified by TLC (thin layer development conditions (petroleum ether: ethyl acetate = 5:1)); the reaction was completed, and the reaction solution was Cool and crystallize at 0°C to 5°C for 2 hours, filter, wash the solid with an appropriate amount of acetonitrile, and dry it in vacuum at 65°C to 70°C for 6 hours to obtain 95 g of a light yellow crystalline powder solid with a yield of 83.1% and an HPLC content of 98.9%. Table 1 is compound Ⅰ 1 elemental analysis.

[0023] HPLC method: using octadecylsilane bonded silica gel as filler, buffer solution (2.7g / ...

Embodiment 2

[0029] Example 2 Compound I 1 Preparation of sodium salt

[0030] 100mL three-neck flask, add Ⅰ 1 Compound 53g and ethanol 400mL, at room temperature, add 22mL of 50% sodium hydroxide solution, stir at 45°C-50°C for 30min, stand at 5°C-10°C overnight, filter, use cold ethanol for solid, vacuum at 70°C-75°C Drying, white crystalline powdery solid 49.4g, yield: 89.6%, HPLC content 99.6%.

Embodiment 3

[0031] Example 3 Compound I 2 preparation of

[0032] With reference to the method of Example 1, ethanesulfonyl chloride was used instead of methanesulfonyl chloride to obtain 87g of white crystalline solid compound I 2 , HPLC content 97.4% (method is the same as embodiment 1). Table 2 is compound Ⅰ 2 elemental analysis.

[0033]

[0034] Table 2

[0035] 1 H—NMR (500MHz, CH 3 OH-d 3 / TMS):

[0036] δ H (ppm): 1.226(2H, m) 2.379(3H, s), 3.458(3H, t, J=7.5Hz; J=1.5Hz, J=8.0Hz), 4.978(2H, s), 6.739(1H, s), 7.109 (2H, d, J = 8.0Hz); 7.718 (2H, d, J = 8.0Hz); 7.471 (2H, d, J = 8.5Hz); 7.898 (2H, d, J = 8.5Hz)

[0037] MS: m / z: 474.5 (M+H) + .

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PUM

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Abstract

The invention discloses a celecoxib derivative with a structure shown as a formula (I) or a pharmaceutically acceptable salt thereof and a preparation method and application of the derivative. The disclosed compound can be used as a substitute of celecoxib and can exist as a hydrate or a solvent, and the problems are solved that existing celecoxib medicaments are insoluble in water, poor in dissolution performance and low in in-vivo absorption rate. The structure-function relationship of celecoxib is analyzed and studied, and it is confirmed that compared with esterification of nitrogen-containing derivatives, sulfur-containing derivatives, oxy-ethers and alcoholic hydroxyl functional groups and other structural transformation, the disclosed celecoxib sulfonamide derivative has better medicinal bioactivity.

Description

technical field [0001] The invention relates to the technical fields of medicinal chemistry and medicine, in particular to a celecoxib derivative and its preparation method and application. Background technique [0002] For a long time, people have suffered from various pains, such as migraine, arthritis, etc. According to reports, in the United States, about 1 / 6 people suffer from various arthritis, among which osteoarthritis and rheumatoid arthritis Inflammation is the most common and difficult to cure, and the disability rate is quite high. In order to protect patients from the torment of inflammation, various therapeutic drugs have been used clinically, the most common of which are non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs have been used clinically for more than 200 years, and their antipyretic, analgesic, and anti-inflammatory effects have been widely recognized clinically, especially as the drug of choice for controlling the symptoms of osteoarthritis and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/12A61K31/4164A61P29/00
CPCC07D231/12A61P29/00
Inventor 刘经星徐奎牛春霞
Owner ANHUI HEALSTAR PHARM CO LTD
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