Application of Harrisotone A O-(diethylamino)ethyl derivative and O-(piperazine) ethyl derivative composition to anti-hepatic fibrosis drug

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: 2017-03-15
NANJING GUANGKANGXIE BIOLOGICAL MEDICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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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  • Application of Harrisotone A O-(diethylamino)ethyl derivative and O-(piperazine) ethyl derivative composition to anti-hepatic fibrosis drug
  • Application of Harrisotone A O-(diethylamino)ethyl derivative and O-(piperazine) ethyl derivative composition to anti-hepatic fibrosis drug
  • Application of Harrisotone A O-(diethylamino)ethyl derivative and O-(piperazine) ethyl derivative composition to anti-hepatic fibrosis drug

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Experimental program
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Effect test

Embodiment 1

[0015] The preparation of embodiment 1 compound Harrisotone A

[0016] The preparation method of compound Harrisotone A (I) refers to the literature published by Sheng Yin et al. (Sheng Yin et al., 2009.Harrisotones A–E, five novel prenylated polyketides with a rarespirocyclic skeleton from Harrisonia perforata.Tetrahedron 65(2009) 1147–1152 )Methods.

[0017]

Embodiment 2

[0018] The synthesis of the O-bromoethyl derivative (II) of embodiment 2 Harrisotone A

[0019] Compound I (472 mg, 1.00 mmol) was dissolved in 15 mL of benzene, and tetrabutylammonium bromide (TBAB) (0.08 g), 1,2-dibromoethane (3.760 g, 20.00 mmol) and 6 mL of 50% sodium hydroxide solution. The mixture was stirred at 35 °C for 3 h. After 3h, 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 twice with water and saturated brine 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=100:1.5, v / v), the brown concentrated elution band was collected and the solvent was evaporated to obtain a yellow powder of compound II (602mg, 76%) .

[00...

Embodiment 3

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

[0024] Compound II (396mg, 0.5mmol) was dissolved in 15mL of acetonitrile, anhydrous potassium carbonate (345mg, 2.5mmol), potassium iodide (84mg, 0.5mmol) and diethylamine (2920mg, 40mmol) were added thereto, and the mixture was heated to reflux for 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=100:1.5, v / v), and the concentrated brown elution band was collected and concentrated to give Compound III as a pale yellow solid (246.1mg, 64%) .

[0...

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Abstract

The invention relates to the field of organic synthesis and pharmaceutical chemistry, and discloses a composition comprising a Harrisotone A O-(diethylamino)ethyl derivative (III) and an O-(piperazine) ethyl derivative (IV) according to the mass ratio of 65:35 and a method for preparing the composition by mixing compounds according to the mass ratio of 65:35. Pharmacological experiments indicate that the composition at a concentration of 20 microgram/ml can remarkably inhibit NIH/3T3 proliferation and transforming growth factor-beta 1 induced fibroblast proliferation and has the function of resisting hepatic fibrosis, so that the invention further provides an application of the composition comprising the Harrisotone A O-(diethylamino)ethyl derivative (III) and the O-(piperazine) ethyl derivative (IV) according to the mass ratio of 65:35 to preparation of an anti-hepatic fibrosis drug.

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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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/496A61P1/16C07D295/088C07C217/12C07C213/02A61K31/132
CPCA61K31/496A61K31/132C07C45/64C07C213/02C07C217/12C07D295/088A61K2300/00C07C49/753
Inventor 陆贤
Owner NANJING GUANGKANGXIE BIOLOGICAL MEDICAL TECH
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