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7-acyl-15-oxo-spiraea lactone derivative as well as preparation method and applications thereof

An acetyl and formyl technology, which is applied in the application field of preparing anti-tumor drugs, can solve the problems of strong drug resistance of tumor cells, drug resistance of cancer cells, and difficulty in effectively inhibiting the development or metastasis of cancer.

Inactive Publication Date: 2013-07-10
THE KEY LAB OF CHEM FOR NATURAL PROD OF GUIZHOU PROVINCE & CHINESE ACADEMY OF SCI +2
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Currently, clinically applied cancer treatment methods include surgery, radiotherapy and chemotherapy, but these methods are difficult to effectively inhibit the development or metastasis of cancer
Radiotherapy and chemotherapy are nonselective, have severe side effects on normal tissues, and can induce drug resistance in cancer cells
In addition, mutations or deletions of multiple genes in cancer cells may also lead to strong drug resistance in tumor cells

Method used

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  • 7-acyl-15-oxo-spiraea lactone derivative as well as preparation method and applications thereof
  • 7-acyl-15-oxo-spiraea lactone derivative as well as preparation method and applications thereof
  • 7-acyl-15-oxo-spiraea lactone derivative as well as preparation method and applications thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] a: in N 2 Oxalyl chloride ((COCl) 2 , 2.0eq, 28ul) into 10ml of dry dichloromethane (DCM), stirred at 0°C, slowly added N, N-dimethylformamide (DMF, 2.0eq, 23ul) dropwise, after the addition was completed, in After stirring at 0°C for 30 min, inject 50 mg of compound 1 (dissolved in 5 ml of dichloromethane solution) into the reaction system, move it to room temperature and stir for 2 hours, track it with TLC, and find that the raw material disappears, add 20 ml of water to quench Reaction, separate the dichloromethane layer, continue to extract the water layer with 20ml of dichloromethane once, combine the dichloromethane layers, wash with saturated brine, dry over anhydrous sodium sulfate, concentrate, and obtain compound 1a through simple silica gel column chromatography (50.9 mg, 94% yield).

[0032] b: compound 1 (50mg), 4-dimethylaminopyridine (DMAP, 0.5eq, 9.2mg) was placed in a dry reaction bottle, and the sample was dissolved with 10ml of dry dichloromethane ...

Embodiment 2

[0035] Compound spectral data:

[0036] compound ( 1a ): 7-formylacyl-15-oxospirandrolactone, 1 H-NMR (400MHz, CDCl 3 ) δ: 8.05(1H, s), 5.95(1H, d, J=1.4Hz), 5.43(1H, dd, J=4.4, 10.8Hz), 5.25(1H, d, J=1.4Hz), 4.24( 1H, dd, J=2.4, 11.6Hz), 4.12(1H, d, J=11.6Hz), 3.14(1H, m), 2.81(1H, brs), 2.16-2.27(4H, m), 1.85-1.92 (1H, m), 1.60-1.78(5H, m), 1.53-1.57(1H, m), 1.33-1.48(3H, m), 1.18-1.26(1H, m), 0.95(3H, s). 13 C-NMR (100MHz, CDCl 3 ) δ: 200.6, 173.7, 160.4, 147.3, 117.3, 76.4, 70.6, 48.7, 46.4, 45.7, 44.6, 40.6, 37.3, 35.6, 32.8, 26.9, 25.8, 23.7, 23.4, 27 m / z 358.1781 [M] + (C 21 h 26 o 5 , calcd 358.1780).

[0037] compound ( 1b ): 7-acetylacyl-15-oxospirandrolactone, 1 H-NMR (400MHz, CDCl 3 ) δ: 5.84(1H, d, J=1.6Hz), 5.22(1H, dd, J=4.4, 11.6Hz), 5.15(1H, d, J=1.6Hz), 4.15(1H, dd, J=3.6 , 11.6Hz), 4.13(1H, d, J=11.6Hz), 3.05(1H, m), 2.72(1H, t, J=2.8, 2.8Hz), 2.05-2.16(3H, m), 1.92(3H , s), 1.68-1.82(1H, m), 1.08-1.68(11H, m), 0.86(3H, s). 13 C-NMR (100...

Embodiment 3

[0057] Inhibitory effects of compounds on various tumor cell lines:

[0058] (1) Experimental method

[0059] 1. Inoculate cells: Use culture medium (DMEM or RMPI1640) containing 10% fetal bovine serum to prepare a single cell suspension, inoculate 5000-10000 cells per well into a 96-well plate with a volume of 100 μl per well, and adherent cells in advance 12 hour inoculation.

[0060] 2. Add the compound solution to be tested (fixed concentration of 40 μM for primary screening, at which concentration the compound that inhibits the growth of tumor cells near 50% is set to enter the gradient rescreening at 5 concentrations), the final volume of each well is 200 μl, and each treatment is set at 3 multiple holes.

[0061] 3. Color development: After incubating at 37 degrees Celsius for 48 hours, add 20 μl of MTT solution to each well. Continue to incubate for 4 hours, terminate the culture, discard the culture supernatant in the well, add 200 μl of SDS solution (10%) to e...

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Abstract

The invention provides a 7-acyl-15-oxo-spiraea lactone derivative which is a medicinal composition of medicinal active ingredients, a preparation method of the derivative, an application of the derivative in preparation of medicaments for resisting hepatitis C virus, and an application of the derivative in preparation of antivirus medicaments. In the process of studying plant antitumor natural products, 7-acyl-15-oxo-spiraea lactone is discovered to have activity of resisting various tumor cell strains, and most derivatives are stronger than a primer 15-oxo-spiraea lactone (1). The 7-acyl-15-oxo-spiraea lactone derivative is subjected to an activity test for inhibiting a Wnt signal channel, and the antitumor activity of the 7-acyl-15-oxo-spiraea lactone derivative is discovered to be in positive correlation with the activity of the 7-acyl-15-oxo-spiraea lactone derivative for inhibiting the Wnt signal channel.

Description

technical field [0001] The invention belongs to the field of medicines, in particular, it relates to a meadowsweet diterpene 7-acyl-15-oxospirandrolide derivative, a pharmaceutical composition which is an active ingredient of a medicine, a preparation method thereof, and a method for preparing anti- Application in tumor medicine. Background technique [0002] The incidence of tumor (cancer) is on the rise and has become the number one killer of human health. According to the forecast of the World Health Organization: by 2020, the number of cancer patients in the world will reach 15 million. According to the recent data released by the Ministry of Health of our country, whether in urban or rural areas, the incidence of cancer has surpassed cardiovascular diseases and has risen to the first place. Currently, clinically applied cancer treatment methods include surgery, radiotherapy and chemotherapy, but these methods are difficult to effectively inhibit the development or met...

Claims

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Application Information

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IPC IPC(8): C07D311/94C07D407/12C07D409/12A61K31/366A61K31/381A61P35/00
Inventor 郝小江晏晨刘海洋何红平李林何小丽
Owner THE KEY LAB OF CHEM FOR NATURAL PROD OF GUIZHOU PROVINCE & CHINESE ACADEMY OF SCI
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