Applications of composition of Virosaine A piperazinyl derivative and Virosaine A imidazolyl derivative in medicines for resisting hepatic fibrosis

A liver fibrosis and composition technology, applied in the fields of organic synthesis and medicinal chemistry, can solve the problems of lack of clinical treatment methods

Inactive Publication Date: 2016-09-07
NANJING FUHAIAOSAI PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In recent years, some anti-hepatic fibrosis treatments have emerged, including chemical drugs, biological agents, traditional Chinese medicine and gene therapy, etc., but the ideal clinical treatment methods are still lacking (Liu Ping. Strengthen the research on the mechanism of anti-hepatic fibrosis. Chinese liver disease Magazine, 2005, 8(13): 561)

Method used

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  • Applications of composition of Virosaine A piperazinyl derivative and Virosaine A imidazolyl derivative in medicines for resisting hepatic fibrosis
  • Applications of composition of Virosaine A piperazinyl derivative and Virosaine A imidazolyl derivative in medicines for resisting hepatic fibrosis
  • Applications of composition of Virosaine A piperazinyl derivative and Virosaine A imidazolyl derivative in medicines for resisting hepatic fibrosis

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Experimental program
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Effect test

Embodiment 1

[0014] The preparation of embodiment 1 compound Virosaine A

[0015] The preparation method of compound Virosaine A (I) refers to the literature published by Bing-Xin Zhao et al. (Bing-Xin Zhao et al., 2012. Virosaines A and B, Two New Birdcage-Shaped Securinega Alkaloids with an Unprecedented Skeleton from Flueggea virosa. Organic Letters 14(2012) 3096–3099).

[0016]

Embodiment 2

[0017] The synthesis of the O-bromoethyl derivative (II) of embodiment 2 Virosaine A

[0018] Compound I (235 mg, 1.00 mmol) was dissolved in 20 mL of benzene, tetrabutylammonium bromide (TBAB) (0.08 g), 1,2-dibromoethane (3.760 g, 20.00 mmol) and 5 mL of 50% sodium hydroxide solution. The mixture was stirred at 35 °C for 8 h. After 8 hours, the reaction solution was poured into ice water, extracted twice with dichloromethane immediately, and the organic phase solutions were combined. Then the organic phase solution was washed with water and saturated brine three times successively, then dried with anhydrous sodium sulfate, and finally concentrated under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography (mobile phase: petroleum ether / acetone=100:1.0, v / v), the brown concentrated elution band was collected and the solvent was evaporated to obtain a brown powder of Compound II (261mg, 78%) .

...

Embodiment 3

[0023] The synthesis of the O-(piperazinyl) ethyl derivative (III) of embodiment 3 Virosaine A

[0024] Compound II (171mg, 0.5mmol) was dissolved in 20mL of acetonitrile, anhydrous potassium carbonate (690mg, 5.0mmol), potassium iodide (168mg, 1.0mmol) and anhydrous piperazine (3446mg, 40mmol) were added thereto, and the mixture was heated to reflux 3h. After the reaction, the reaction solution was poured into ice water, extracted twice with an equal amount of dichloromethane, and the organic phases were combined. The combined organic phases were successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography (mobile phase: petroleum ether / acetone=100:1.0, v / v), the brown concentrated elution band was collected and the solvent was evaporated to obtain compound III as a light brown solid (123.2mg, ...

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Abstract

The invention relates to the fields of organic synthesis and pharmaceutical chemistry, and discloses and provides a composition prepared from Virosaine A piperazinyl derivative and Virosaine A imidazolyl derivative at the weight ratio of 25 to 75, and a method for preparing the composition by mixing the two compounds at the weight ratio of 25 to 75. The pharmacological experiment proves that the composition provided by the invention at 20 [mu] g / ml can obviously inhibit the proliferation of NIH / 3T3 and the proliferation of fibroblasts induced by transforming growth factor-beta 1, and has the effect of resisting hepatic fibrosis, and therefore, the invention further provides the applications of the composition prepared from the Virosaine A piperazinyl derivative and the Virosaine A imidazolyl derivative at the weight ratio of 25 to 75 in preparing medicines for resisting hepatic fibrosis.

Description

technical field [0001] The invention relates to the fields of organic synthesis and medicinal chemistry, in particular to a composition, a preparation method and an application thereof. Background technique [0002] Liver fibrosis is a dynamic process from chronic liver injury to liver cirrhosis, manifested in the synthesis and secretion of a large amount of extracellular matrix (ECM), while the degradation is absolutely or relatively insufficient, resulting in the diffuse deposition of ECM in the liver. It starts with necrosis of hepatocytes (HC), followed by inflammatory response, release of fibrogenesis mediators, activation of hepatic stellate cells (FSC), and finally, the synthesis and degradation of liver connective tissue components are obviously out of balance. Liver fibrosis is a common pathological process of many chronic liver diseases and an important factor affecting prognosis. [0003] In the past 20 years, the study of liver fibrosis has made great progress, ...

Claims

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Application Information

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IPC IPC(8): A61K31/496A61K31/439C07D498/22A61P1/16
CPCA61K31/439A61K31/496C07D498/22A61K2300/00
Inventor 王卓婷
Owner NANJING FUHAIAOSAI PHARMA CO LTD
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