Coumarin macromolecule polymer with anti-tumor activity and preparation method of coumarin macromolecule polymer

A technology of polymer copolymers and coumarins, which is applied in the direction of organic active ingredients, antineoplastic drugs, and medical preparations of non-active ingredients, etc., to achieve the effects of enhancing inhibition, reducing toxicity, and promoting inhibition

Inactive Publication Date: 2013-04-03
NORTHWEST NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, until now, there have been no reports on the preparation of anticancer drugs by linking the above two anticancer drugs to the polymer carrier HPMA.

Method used

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  • Coumarin macromolecule polymer with anti-tumor activity and preparation method of coumarin macromolecule polymer
  • Coumarin macromolecule polymer with anti-tumor activity and preparation method of coumarin macromolecule polymer
  • Coumarin macromolecule polymer with anti-tumor activity and preparation method of coumarin macromolecule polymer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Preparation of 7-hydroxycoumarin monomer: weigh 7-hydroxycoumarin (1 mmol, 160 mg), dissolve in 20 ml of dichloromethane, cool to about 0 °C; weigh methacryloyl chloride (1.5 mmol, 150 mg), was added dropwise to a solution of 7-hydroxycoumarin in dichloromethane; weighed triethylamine (0.2 mmol, 0.02 g), added dropwise to the above solution, and then stirred overnight in an ice-water bath , to obtain a clear dark red solution; the reaction solution was evaporated on a rotary evaporator to remove the solvent to obtain a light red solid, column chromatography (ethyl acetate:petroleum ether=1:8 (v / v)) to obtain a white solid, namely For 7-hydroxy coumarin monomer. Yield 193 mg (85 %).

[0055] 1 H NMR (400 MHz, D 2 O, δ, ppm): 7.73 (d, 1H, Ar- H) ; 7.52 (d, 1H, Ar- H ); 7.27 (s, 1H, Ar- H ); 7.08-7.16 (m, 1H, Ar- H ); 6.42 (s, 1H, H -CH = C); 6.39 (s, 1H, Ar- H ); 5.83 (s, 1H, H -CH = C); 2.08 (s, 3H, -C H 3 ). 13 C NMR (400MHz, DMSO, δ, ppm): 165.07; 160...

Embodiment 2

[0059] Preparation of 7-hydroxycoumarin monomer: same as Example 1.

[0060] Preparation of sulfadiazine monomer: weigh sulfadiazine (1 mmol, 250 mg), dissolve in a mixed solution of acetone and sodium hydroxide (1:1.5 (v / v)), cool to about 0°C; Acid chloride (1.5 mmol, 150 mg) was added dropwise to the above cooled solution, stirred overnight in an ice-salt bath, and a yellow precipitate was obtained; after suction filtration and drying, use methanol-water mixed solvent (2:0.5 (v / v) ) recrystallized, then suction filtered, and dried in a vacuum oven at 40 °C for 72 hours to obtain a light yellow solid which is the sulfadiazine monomer (B). Yield was (230 mg, 72%).

[0061] 1 H NMR (400 MHz, DMSO, δ, ppm ): 11.69 (s, 1H, -CO-N H -), 10.14 (s, 1H, -SO 2- N H -), 8.48-8.49 (d, 2H, pyrimidine- H ), 7.92 (q, 4H, Ar- H ), 7.0 (s, 1H, pyrimidine- H ), 5.82 (s, 1H, H-CH = C), 5.56 (s, 1H, H -CH = C), 1.92 (s, 3H, CH 2 = C-C H 3 ). 13 C NMR (400 MHz, DMSO, δ, ppm): 167....

Embodiment 3

[0065] Preparation of 7-hydroxycoumarin monomer: same as Example 1.

[0066] Preparation of coumarin-based polymer copolymer (1): Weigh 7-hydroxycoumarin monomer (8%, 23 mg, 0.1 mmol), HPMA (92%, 165 mg, 1.15 mmol) in a reaction flask , add 0.5ml of DMSO, stir to make it completely dissolved, then add 1ml of acetone and stir evenly; then add azobisisobutyronitrile (8%, wt, 15 mg,); vacuumize and fill with nitrogen, at 60℃ Polymerized for 24 hours. Dissolve the polymerization reaction solution with acetone precipitation methanol (2:1 (v / v)) for 3 times and then filter the precipitate to obtain a white solid. Centrifuge to remove small molecules, and dry the liquid after centrifugation to obtain a white solid that is a polymer drug (1). The yield was (138 mg, 73 %).

[0067] 1 H NMR (400 MHz, DMSO, δ, ppm): 8.10 (1H, Ar- H of UMB), 7.88 (1H, Ar- H of UMB), 7.25 (1H. Ar- H of UMB), 7.21 (1H, Ar- H of UMB), 6.53 (1H, Ar- H of UMB), 3.71 (1H, CH 3 C H (OH)CH 2 NH- ...

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Abstract

The invention provides a coumarin macromolecule polymer with anti-tumor activity. 7-hydroxycoumarin or 7-hydroxycoumarin and sulfadiazine is or are connected to N-(2-hydroxypropyl) methacrylamide through a polymerization mode to form a macromolecule copolymer with good biological compatibility. The macromolecule copolymer is used for connecting the 7-hydroxycoumarin with anti-tumor activity and the sulfadiazine to a tumor targeted drug carrier N-(2-hydroxypropyl) methacrylamide to ensure that the anti-tumor activity is overlapped, further the inhibition of the macromolecule polymer to tumors is promoted, and the standing time of anti-tumor drugs in tumors is greatly prolonged; and meanwhile, by adopting the macromolecule carrier HPMA (hydroxypropyl methacrylate), the toxicity of the anti-cancer drugs is reduced, and the hurt to normal tissues is decreased. The coumarin macromolecule polymer can be used for preventing and treating cancers such as gastric cancer, colon cancer, hepatoma and the like.

Description

Technical field [0001] The present invention is a compound synthesis and application field, involving a fragrant polymer with anti -tumor activity; the present invention also involves the preparation method of the fragrant beanin polymer. Background technique [0002] Cancer has become one of the main threats of human health and has shown a significant upward trend.The main methods of treating cancer today include radiotherapy, chemotherapy, surgical therapy and gene therapy.Among them, radiotherapy and chemotherapy are extremely important non -surgical therapies, but radiotherapy and chemotherapy also cause severe damage to normal cells of the body while killing tumor cells.The existing anticancer drugs are small molecular drugs. During the circulation of the body, it is quickly discharged from the body and does not achieve the expected treatment effect.So far, there have been no special effects of prevention and treatment of cancer or tumor. [0003] Cottonin -type compounds ca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F220/58C08F222/14C08F220/60A61K47/48A61K31/37A61K31/635A61P35/00A61K47/58
Inventor 袁建超宋凤英谢小利贾宗栗静袁兵年王福州
Owner NORTHWEST NORMAL UNIVERSITY
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