Magnolol derivative, honokiol derivative and preparation method and application thereof

A technology of phenol derivatives and magnolol, which is applied in the fields of magnolol derivatives and honokiol derivatives and their pharmaceutical applications, can solve the problems of poor water solubility, low bioavailability, and restrictions on wide application, and achieve good antibacterial Thrombosis, reducing the effect of cerebral ischemia or cerebral ischemia-reperfusion injury

Active Publication Date: 2013-05-22
BEIJING HONGHUI MEDITECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, magnolol and honokiol have poor water solubility and low bioavailability, which seriously limit their wide application in medicine and need to be improved

Method used

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  • Magnolol derivative, honokiol derivative and preparation method and application thereof
  • Magnolol derivative, honokiol derivative and preparation method and application thereof
  • Magnolol derivative, honokiol derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1 [(S)-2,6-N-Boc-diamino-1-hexanoic acid]-[5,5'-dipropenyl-2'-hydroxy-2-biphenol] ester (compound 1) preparation of

[0052] Boc-Lys(Boc)-OH (3.097g, 8.9mmol) was dissolved in 80ml of dichloromethane, and DCC was added and stirred for 10min. Magnolol (1.9737 g, 7.3 mmol) was added to the solution and stirred at room temperature for 15 hours. The precipitate was filtered, the filtrate was concentrated, and residual column chromatography (PE:EA=10:1) obtained 2.3 g of compound 1.

[0053] Compound 1: C 34 h 46 N 2 o 7 =594.33, MS: 595.2[M+H] + . 1 H-NMR (300MHz, DMSO 3 )δ7.21-7.16 (2H, t), 7.11 (1H, s), 6.99-6.91 (2H, t), 6.81-6.76 (3H, t), 6.0-5.83 (2H, m), 5.09-4.98 ( 4H, m), 3.87-3.82 (1H, t), 3.39-3.23 (4H, m), 2.79 (2H, 1s), 1.37 (18H, s), 1.28-1.04 (8H, m).

Embodiment 2

[0054] Example 2 [(S)-2,6-diamino-1-hexanoic acid]-[5,5'-dipropenyl-2'-hydroxy-2-biphenol] ester hydrochloride (compound 2) preparation of

[0055] Add compound 1 (2.3g, 3.9mmol) and a saturated solution of hydrogen chloride in dioxane (50ml) into a 100ml single-necked bottle, stir at room temperature for 3 hours, remove the solvent under reduced pressure, and the crude product is subjected to column chromatography (C 18 , eluent: water / methanol=30%-50%) to obtain 1.7g of compound 2.

[0056] Compound 2: C 24 h 31 Cl 2 N 2 o 2 =449.18, MS: 395.2[M+H-2HCl] + . 1 H--NMR (300MHz, DMSO) δ9.44 (1H, s), 8.64 (3H, s), 8.00 (3H, s), 7.85-6.83 (6H, m), 6.08-5.86 (2H, m), 5.16-5.01 (4H, m), 4.01 (1H, m), 3.42-3.26 (4H, m), 2.62 (2H, m), 156-138 (4H, m), 117-099 (4H, m)

Embodiment 35

[0057] Example 35,5'-Dipropenyl-3-nitro-1,1'-biphenyl-2,2'-diphenol and 5,5'-dipropenyl-3,3'-dinitro- Preparation of 2,2'-biphenol (compounds 3a and 3b)

[0058] Add a solution of magnolol (0.5g, 1.88mmol) in acetic anhydride (500ml) into a 100ml single-necked bottle, and slowly add cold fuming nitric acid (5.9ml) and glacial acetic acid (6ml) dropwise at 0°C under constant stirring. anhydride (5ml) solution. After the dropwise addition, the reaction solution was poured into ice water, allowed to rise to room temperature, extracted with diethyl ether (500ml×3), dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The obtained crude product was separated by column chromatography (silica gel: 200-300 mesh, eluent: petroleum ether-petroleum ether / ethyl acetate 100:1) to obtain 150 mg of compound 3a and 250 mg of compound 3b.

[0059] Compound 3a: C 18 h 17 NO 4 =311.12, MS: 329[M+NH 4 ] + , 1 H-NMR (300MHz, CDCl 3 )δ8.01 (1H,...

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Abstract

The invention discloses a magnolol derivative, a honokiol derivative and a preparation method and an application thereof, and belongs to the field of magnolol or honokiol derivatives. Aiming at the defects that the magnolol and the honokiol are poor in water solubility, the invention structurally modifies or transforms the magnolol and the honokiol, introduces corresponding functional molecules and obtains the magnolol or honokiol derivative shown in formula I. Water solubility tests show that the magnolol or honokiol derivative shown in formula I has good water solubility. Pharmacodynamic tests show that the magnolol or honokiol derivative shown in formula I has an excellent antithrombosis activity and has a protection capability to cerebral ischemia-reperfusion injury.

Description

technical field [0001] The present invention relates to phenolic derivatives, especially magnolol derivatives and honokiol derivatives. The present invention further relates to their preparation methods and their application in the preparation of antithrombotic, anti-cerebral ischemia or cerebral ischemia-reperfusion injury protection The use in medicine belongs to the field of magnolol derivatives and honokiol derivatives and their medical applications. Background technique [0002] Magnolol and honokiol are the main active ingredients of the traditional Chinese medicine Magnolia officinalis. The chemical structural formula of magnolol and honokiol is figure 1 shown. In 1930, Japanese Sugii first isolated magnolol from the bark of Magnolia officinalis in China. In 1989, Meng Lizhen and others in China also isolated honokiol from magnolia bark (Chinese patent medicine: 1989, 11 (8): 223.). [0003] Magnolol and honokiol have a wide range of pharmacological effects such as...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C271/22C07C269/06C07C229/26C07C227/20C07C237/04C07C231/12C07C215/78C07C213/02A61K31/27A61K31/223A61K31/167A61K31/136A61P7/02A61P9/10
Inventor 王银叶刘晔张平平童卫民蔡阳
Owner BEIJING HONGHUI MEDITECH CO LTD
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