Application of composition of derivatives of Artalbic acid in preparation of anti-liver fibrosis medicine

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: 2016-10-26
南京海澳斯生物医药科技有限公司
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  • 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 id

Method used

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  • Application of composition of derivatives of Artalbic acid in preparation of anti-liver fibrosis medicine
  • Application of composition of derivatives of Artalbic acid in preparation of anti-liver fibrosis medicine
  • Application of composition of derivatives of Artalbic acid in preparation of anti-liver fibrosis medicine

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Embodiment 1

[0014] The preparation of embodiment 1 compound Artalbic acid

[0015] The preparation method of compound Artalbic acid (I) refers to the literature published by Antonella Maggio et al. (Antonella Maggio et al., 2011. Artalbic acid, a sesquiterpene with an unusual skeleton from Artemisia alba (Asteraceae) from Sicily. Tetrahedron Letters, 52 (2011) 4543–4545) approach.

[0016]

Embodiment 2

[0017] Synthesis of O-bromoethyl derivative (II) of embodiment 2 Artalbic acid

[0018] Compound I (266 mg, 1.00 mmol) was dissolved in 10 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 40 °C for 16 h. After 16 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 for 5 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 (272mg, 73%) .

...

Embodiment 3

[0023] The synthesis of the O-(dichloroethylamino) ethyl derivative (III) of embodiment 3 Artalbic acid

[0024] 1. Synthesis of O-(dihydroxyethylamino)ethyl derivatives of Artalbic acid

[0025] Compound II (187 mg, 0.5 mmol) was dissolved in 20 mL of acetonitrile, anhydrous potassium carbonate (690 mg, 5.0 mmol), potassium iodide (252 mg, 1.5 mmol) and diethanolamine (1051 mg, 10 mmol) were added thereto, and the mixture was heated to reflux for 1 h. 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 washed successively 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), and the ...

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Abstract

The invention discloses an application of O-(dichloroethylamino)-ethyl and O-(bis(2-methylthioethyl) amino)ethyl derivatives of Artalbic acid in preparation of an anti-liver fibrosis medicine, relating to the fields of organic synthesis and pharmaceutical chemistry. The invention discloses and provides a composition composed of O-(dichloroethylamino)-ethyl and O-(bis(2-methylthioethyl) amino)ethyl derivatives of Artalbic acid in a mass ratio of 30:70 and a method for preparing the composition by mixing the compounds in a mass ratio of 30:70. Pharmacological experiments show that the composition provided by the invention can obviously inhibit NIH/3T3 proliferation and transforming growth factor-beta 1 induced fibroblast proliferation at 20mu g/ml and has an anti-liver fibrosis effect. Therefore, the invention also provides an application of the composition composed of the O-(dichloroethylamino)-ethyl and O-(bis(2-methylthioethyl) amino)ethyl derivatives of Artalbic acid in a mass ratio of 30:70 in preparation of the anti-liver fibrosis medicine.

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): A61K31/195A61P1/16C07C217/12C07C323/25
CPCA61K31/195C07C217/12C07C323/25A61K2300/00
Inventor 丁秋菊
Owner 南京海澳斯生物医药科技有限公司
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