Derivative composition of benzimidazole and dichloroethylamino of Psiguadial A for anti-hepatic fibrosis

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

Inactive Publication Date: 2017-05-31
苏州贺澳德生物医药科技有限公司
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  • 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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  • Derivative composition of benzimidazole and dichloroethylamino of Psiguadial A for anti-hepatic fibrosis
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  • Derivative composition of benzimidazole and dichloroethylamino of Psiguadial A for anti-hepatic fibrosis

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Effect test

Embodiment 1

[0015] Example 1 Preparation of Compound Psiguadial A

[0016] The preparation method of compound Psiguadial A (I) refers to the literature published by Meng Shao et al. (Meng Shao et al., 2010.Psiguadials A and B, Two Novel Meroterpenoids with UnusualSkeletons from the Leaves of Psidium guajava.Organic Letters 12(2010)5040- 5043) method.

[0017]

Embodiment 2

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

[0019] Compound I (474 ​​mg, 1.00 mmol) was dissolved in 20 mL of benzene, tetrabutylammonium bromide (TBAB) (0.16 g), 1,2-dibromoethane (7.520 g, 40.00 mmol) and 12 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=100:0.5, v / v), the brown concentrated elution band was collected and the solvent was evaporated to obtain a brown powder of Compound II (502mg, 73%) ...

Embodiment 3

[0024] Synthesis of O-(benzimidazolyl)ethyl derivative (III) of Psiguadial A of embodiment 3

[0025] Compound II (344mg, 0.5mmol) was dissolved in 25mL of acetonitrile, anhydrous potassium carbonate (690mg, 5.0mmol), potassium iodide (168mg, 1.0mmol) and benzimidazole (4720mg, 40mmol) were added thereto, and the mixture was heated to reflux for 3h . After the reaction was completed, the reaction solution was poured into 20 mL of ice water, extracted three times 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=100:0.5, v / v), the yellow concentrated elution band was collected and the solvent was evaporated to obtain a yellow powder of c...

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Abstract

The invention relates to the field of organic synthesis and drug chemicals. The invention discloses a composition prepared from O-(benzimidazole) ethyl derivative (III) and O-(dichloroethylamino) ethyl derivative (IV) of Psiguadial A according to mass ratio of 20: 80 and a preparation method of the composition by mixing above compounds according to mass ratio of 20: 80. The pharmacological experiment indicates that the composition provided by the invention can significantly inhibit the NIH/3T3 propagation and fibroblast propagation induced by transforming growth factor-beta 1 when its content is 20 ug/ml, and the composition has the anti-hepatic fibrosis effect; therefore, the invention further provides the application of the composition prepared from O-(benzimidazole) ethyl derivative (III) and O-(dichloroethylamino) ethyl derivative (IV) of Psiguadial A according to mass ratio of 20: 80 in preparing the anti-hepatic fibrosis drugs.

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): A61K31/4184A61K31/335A61P1/16C07D313/06C07D405/14
CPCA61K31/4184A61K31/335C07D313/06C07D405/14
Inventor 朱磊磊
Owner 苏州贺澳德生物医药科技有限公司
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