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Scopoletin derivatives with anti-tumor activity, and preparation method and application thereof

A tumor and drug technology, applied in the field of scopolamine derivatives, can solve the problems of unstable metabolism, high effective concentration, and short action time in the body

Inactive Publication Date: 2013-12-18
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although scopoletin has anti-tumor activity, its effective concentration is high, its metabolism in the body is unstable, and its action time is short, which limits its clinical application.

Method used

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  • Scopoletin derivatives with anti-tumor activity, and preparation method and application thereof
  • Scopoletin derivatives with anti-tumor activity, and preparation method and application thereof
  • Scopoletin derivatives with anti-tumor activity, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Preparation of 2,4-dihydroxy-5-methoxybenzaldehyde:

[0049] Add aluminum trichloride (80g, 0.60mol) and anhydrous dichloromethane (400mL) into a 1000mL three-necked flask, then add 1gCTAB, and stir. 2,4,5-Trimethoxybenzaldehyde (20g, 0.10mol) was dissolved in anhydrous dichloromethane (100mL), added dropwise to the reaction flask, and heated to reflux for 4h. Pour the reactant into 500 g of crushed ice to which 100 mL of concentrated hydrochloric acid has been added, stir for 0.5 h, separate the organic layer, wash the organic layer three times with saturated aqueous sodium chloride solution, dry over anhydrous sodium sulfate, evaporate the solvent by rotary evaporation, and recrystallize from toluene , to obtain a light yellow solid (15.50g, 90.42%), mp.145℃.

[0050] 1 H NMR (300MHz, DMSO-d 6 ):δ3.71(3H,s,OCH 3 ), 3.94 (1H, s, OH), 6.50 (1H, s, phenyl1-H), 6.69 (1H, s, phenyl1-H), 9.80 (1H, s, OH), 10.70 (1H, s, CHO) .ESI-MS(m / z):168[M-H] - .

[0051] Preparat...

Embodiment 2

[0063] 3-(4-Chlorophenyl)-N-(6-methoxy-7-hydroxy-2H-1-benzopyran-2-one-3-yl)acrylamide (Ⅰ 2 )

[0064] Referring to the preparation method of Example 1, using p-chlorocinnamic acid and 6-methoxy-7-hydroxy-3-aminocoumarin as raw materials, recrystallized from ethanol to obtain about 120mg, yellow-white powder, yield 81.4%, mp >250°C.

[0065] ESI-MS(m / z):366[M-H]-.

[0066] IR(KBr,cm -1 ):3334(OH);3120(C=C);1708,1677(C=O).

[0067] 1 H NMR (DMSO-d 6 , 300MHz) δ: 3.83 (3H, m, OCH 3 ), 6.81 (1H, s, H8), 7.28 (1H, d, J=13.8Hz, CH), 7.35 (2H, d, J=8.1Hz, Ar-H), 7.51 (1H, s, H5), 7.53(2H,d,J=8.1Hz,Ar-H),7.64(1H,d,J=13.8Hz,CH),8.73(1H,s,H4),9.76(1H,s,NH),10.10( 1H,s,OH).

Embodiment 3

[0069] 3-(4-fluorophenyl)-N-(6-methoxy-7-hydroxy-2H-1-benzopyran-2-one-3-yl)acrylamide (Ⅰ 3 )

[0070] Referring to the preparation method of Example 1, using p-fluorocinnamic acid and 6-methoxy-7-hydroxy-3-aminocoumarin as raw materials, recrystallized from ethanol to obtain about 125mg, yellow powder, yield 75.2%, mp> 250°C.

[0071] ESI-MS(m / z):354[M-H] - .

[0072] IR(KBr,cm -1 ):3331(OH);3144(C=C);1710,1673(C=O).

[0073] 1 H NMR (DMSO-d 6 , 300MHz) δ: 3.83 (3H, m, OCH 3 ), 6.81 (1H, s, H8), 7.23 (1H, d, J=13.8Hz, CH), 7.32 (2H, d, J=8.1Hz, Ar-H), 7.49 (1H, s, H5), 7.54(2H,d,J=8.1Hz,Ar-H),7.67(1H,d,J=13.8Hz,CH),8.86(1H,s,H4),9.84(1H,s,NH),10.17( 1H,s,OH).

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Abstract

The invention relates to the fields of organic synthesis and medicinal chemistry, and particularly relates to scopoletin derivatives having anti-tumor activity and shown in a general formula I or II, a preparation method of the scopoletin derivatives, pharmaceutical compositions including the scopoletin derivatives and application of the scopoletin derivatives and the pharmaceutical compositions. Pharmacodynamic experiments prove that the scopoletin derivatives disclosed by the invention have the anti-tumor activity and can be applied to treatment of a breast cancer, a lung cancer, a colorectal cancer, a cancer of the liver, a gastric cancer, neuroglioma, an ovarian cancer, a cervical cancer, a thyroid cancer, a pancreatic cancer or histiocytic lymphoma.

Description

technical field [0001] The invention relates to the fields of organic synthesis and medicinal chemistry, in particular to a class of scopolamine derivatives, their preparation method, their pharmaceutical composition and their antitumor application. Background technique [0002] Cancer, that is, malignant tumors, is one of the common diseases with the highest mortality rate today due to its difficult detection of early symptoms, rapid development of advanced disease, and easy recurrence and metastasis. Antineoplastic drug research has always been the focus of attention, because traditional cytotoxic drugs mainly act on DNA, RNA, and other common parts that are critical to the life and death of all cells, resulting in low selectivity and high toxicity, causing serious adverse reactions and drug resistance Sexuality and other issues affect its clinical application. Therefore, it is an important research direction for pharmaceutical workers to find new anti-tumor drugs that ar...

Claims

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Application Information

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IPC IPC(8): C07D311/16A61K31/352A61K31/5377A61P35/00
Inventor 夏玉凤陈莉李林虎赵鹏胡经林戴岳
Owner CHINA PHARM UNIV
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