2,3,4,5-tetrasubstituted derivatives of benzyl ethylene class, preparation method and application

A technology of four-substitution and derivatives, which is applied in the field of 2,3,4,5-tetrasubstituted phenylpropene derivatives and their preparation and application, and can solve the problems of limited drug universal applicability, low selectivity, and ineffective curative effect. Satisfactory etc.

Inactive Publication Date: 2007-10-10
ZHEJIANG HISUN PHARMA CO LTD
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

However, the curative effect of drugs for the treatment of tumor diseases is not satisfactory. At present, the anti-tumor drugs used in clinical practi...

Method used

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  • 2,3,4,5-tetrasubstituted derivatives of benzyl ethylene class, preparation method and application
  • 2,3,4,5-tetrasubstituted derivatives of benzyl ethylene class, preparation method and application
  • 2,3,4,5-tetrasubstituted derivatives of benzyl ethylene class, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] Embodiment 1: the preparation of V-c (2-bromo-3,5-dimethoxy-4-(3,4-dichlorobenzyloxy) benzaldehyde)

[0078]

[0079] This example relates to a class of 2,3,4,5-tetrasubstituted phenylpropene derivative key intermediate 2,3,4,5-tetrasubstituted benzene with cytotoxic activity shown in formula (V) General synthesis method of formaldehyde series compounds. It specifically relates to the synthesis of compound 2-bromo-3,5-dimethoxy-4-(3,4-dichlorobenzyloxy)benzaldehyde. The compound 2-bromo-4-hydroxyl-3,5-dimethoxybenzaldehyde (0.85 g, 3.28 mmol) was dissolved in 20 ml of acetone, anhydrous potassium carbonate (1.13 g, 8.22 mmol) was added, and stirred for 10 minutes , and then added 3,4-dichlorobenzyl bromide (0.6 ml, 3.61 mmol) in 10 ml of acetone, and refluxed for 4 hours. Thin-layer chromatography (TLC) showed that the reaction of the raw material was basically complete, cooled to room temperature, filtered to remove potassium carbonate, and distilled off the solve...

Embodiment 2

[0081] Embodiment 2: the preparation of compound V-a (2,3,5-trimethoxy-4-(4-ethoxybenzyloxy) benzaldehyde)

[0082]

[0083] This example relates to a class of 2,3,4,5-tetrasubstituted phenylpropene derivative key intermediate 2,3,4,5-tetrasubstituted benzene with cytotoxic activity shown in formula (V) General synthesis method of formaldehyde series compounds. It specifically relates to the synthesis of compound 2,3,5-trimethoxy-4-(4-ethoxybenzyloxy)benzaldehyde. Add p-ethoxybenzyl bromide (0.51 g, 2.37 mmol) sodium iodide (59 mg, 0.40 mmol) and acetone (15 ml) successively in a 100 ml three-necked flask, then add potassium carbonate (0.82 g, 5.94 mmol) and 4-hydroxy-2,3,5-trimethoxybenzaldehyde (420 mg, 1.98 mmol), refluxed for 3 hours. Cool to room temperature, filter, concentrate the filtrate, and purify by column chromatography (petroleum ether / ethyl acetate=15:1, crude product / silica gel=1:30) to obtain 363 mg of white solid with a yield of 53%.

[0084] Compound V...

Embodiment 3-6

[0085] According to the method with one of embodiment 1-2, prepare embodiment 3-6 compound shown in following table 1:

[0086]

[0087] Table I

[0088]

[0089] List the physicochemical data of each compound in Table 1 below:

[0090] Compound V-b: white solid, Rf (n-hexane / ethyl acetate: 5 / 2) 0.57; 1 H-NMR (400MHz, CDCl 3 ): δ10.29 (1H, s, CHO), 7.62 (1H, d, J=2.0Hz, H-2′), 7.43 (1H, d, J=8.0Hz, H-5′), 7.29 (1H , m, J=8.0, 2.0Hz, H-6'), 7.11 (1H, s, H-6), 5.11 (2H, s, H-7'), 3.93 (3H, s, OCH 3 -2), 3.86 (6H, s, OCH 3 -3, 5).

[0091] Compound V-d: white solid, Rf (n-hexane / ethyl acetate: 5 / 2) 0.51; 1 H-NMR (400MHz, CDCl 3 ): δ10.26 (1H, s, CHO), 7.34 (2H, d, J=8.8Hz, H-3′, 5′), 7.26 (1H, s, H-6), 6.84 (2H, d, J=8.8Hz, H-2', 6'), 5.05(2H, s, H-7'), 4.00(2H, q, J=6.8Hz, OCH 2 CH 3 -4'), 3.87 (6H, s, OCH 3 -3, 5), 1.38 (3H, t, J=6.8Hz, OCH 2 CH 3 -4′).

[0092] Compound V-e: colorless liquid, Rf (n-hexane / ethyl acetate: 5 / 2) 0.61; 1 H-NMR (400MHz, CDCl3): δ...

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Abstract

This invention relates to 2, 3, 4, 5-tetrasubstituted phenyl propylene derivatives with cytotoxicity. This invention also relates to a method for preparing the derivatives, their drug compositions, and their pharmaceutical application. The derivatives can inhibit the bioactivity of prostate cancer cell (PC-3), nasopharyngeal cancer cell (CNE), oral epithelial cancer cell (KB), lung cancer cell (A549), liver cancer cell (BEL-7404), and cervical cancer cell (Hela), thus can be used as anti-tumor drugs.

Description

technical field [0001] The present invention relates to the fields of organic chemistry, medicinal chemistry and pharmacology, specifically, the present invention relates to the preparation method of 2,3,4,5-tetrasubstituted phenylpropenoid derivatives and key intermediates thereof, and for this series of compounds Six tumor cell lines were carried out, such as human prostate cancer cell (PC-3), nasopharyngeal carcinoma cell line (CNE), oral epithelial cancer cell line (KB), human lung cancer cell (A549), human liver cancer cell (BEL-7404 ), human cervical cancer cell (Hela) tumor cell growth inhibitory activity screening. The compounds are found to have a certain activity of inhibiting the growth of tumor cells, and can be expected to be used as antitumor drugs. Background of the invention [0002] At present, due to environmental pollution and other problems brought about by industrial development, the quality of human living environment continues to decline, and the inci...

Claims

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Application Information

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IPC IPC(8): C07C69/708C07C47/575A61K31/216A61P35/00
Inventor 赵昱张丽娟曾苏巫秀美白骅
Owner ZHEJIANG HISUN PHARMA CO LTD
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