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Benzofuran derivative as well as preparation method and application thereof

A technology of benzofuran and derivatives, which is applied in the field of benzofuran derivatives and their preparation, can solve the problems of unseen, small toxic and side effects, strong targeting effect, etc., and achieve good inhibitory effect and good AKT protein kinase Inhibitory effect, strong effect of tumor suppressor activity

Inactive Publication Date: 2021-04-20
苏聪
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention innovatively synthesizes a benzofuran derivative, which has a good inhibitory effect on the activity of AKT protein kinase, and can inhibit the growth of abnormal tumor cells at the same time, with remarkable anti-tumor activity, strong targeting effect, and small toxic and side effects. In order to obtain a new compound that can be used to prepare AKT protein kinase inhibitors, there are no reports of related structures in the prior art

Method used

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  • Benzofuran derivative as well as preparation method and application thereof
  • Benzofuran derivative as well as preparation method and application thereof
  • Benzofuran derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1. Preparation of compound 1

[0034]

[0035] (1) Intermediate 2,3-bis((bromotriphenyl-λ 5 Synthesis of -phosphoryl)methyl)benzene-1,4-diol (compound shown in structural formula 2):

[0036] 2,3-Bis(bromomethyl)benzene-1,4-diol (compound of formula 1) (100 mmol) and triphenylphosphine (210 mmol) were heated under reflux in 160.0 mL of chloroform for 0.5 hours. The reaction mixture was then allowed to cool and the white precipitate formed was filtered off. The filtrate was evaporated to dryness in vacuo, the obtained crude product was dissolved in 50.0 mL of toluene to be slurried, filtered, washed with toluene, the resulting solids were combined and dried under vacuum at 50°C to obtain 66.46 g of an off-white solid with a yield of 81% .

[0037] 1 H-NMR (400MHz, CDCl 3 )δ: 2.60(d, 4H), 6.49(s, 2H), 7.15(m, 12H), 7.44-7.47(m, 18H), 9.68(s, 2H). 13 C-NMR (125MHz, CDCl 3 )δ: 29.58, 118.00, 123.17, 126.49, 131.37, 132.66, 134.54, 147.30.

[0038] (2) Synth...

Embodiment 2

[0050] Example 2. Preparation of compound 2 (compound represented by chemical structural formula 7)

[0051] (1)(2,6-Dibutylbenzo[1,2-b:5,4-b']difuran-3,5-diyl)bis((4-((2-methpropenyl) ) oxy) phenyl) ketone) (compound shown in chemical structure 7) synthesis:

[0052]

[0053] Potassium carbonate (20 mmol) was added to (2,6-dibutylbenzo[1,2-b:5,4-b']difuran-3,5-diyl)bis((4-hydroxyphenyl) ) ketone) (compound of formula 5) (20 mmol) in toluene (80 mL). The mixture was then stirred at 25-30°C for 0.5 hours and heated to reflux, after which 3-chloro-3-methylpropene (45 mmol) was added maintaining the temperature. The reaction mixture was refluxed for 5 hours. The reaction mixture was then cooled to 25-30°C, and the inorganic solids were filtered and washed with toluene (50 mL). The filtrate was collected and concentrated under reduced pressure, followed by flash column chromatography (ethyl acetate as the eluent) to give 9.71 g of an off-white solid in 78.5% yield.

[0054...

Embodiment 3

[0055] Example 3. Preparation of compound 3 (compound represented by structural formula 8)

[0056] (1)(2,6-Dibutylbenzo[1,2-b:5,4-b']difuran-3,5-diyl)bis((4-(2-methylbutoxy) ) phenyl) ketone) (compound of formula 8) synthesis

[0057]

[0058]Potassium carbonate (20 mmol) was added to (2,6-dibutylbenzo[1,2-b:5,4-b']difuran-3,5-diyl)bis((4-hydroxyphenyl) ) ketone) (compound of formula 5) (20 mmol) in toluene (80 mL). The mixture was then stirred at 25-30°C for 0.5 hours and heated to reflux, after which 1-chloro-2-methylbutane (45 mmol) was added maintaining the temperature. The reaction mixture was refluxed for 5 hours. The reaction mixture was then cooled to 25-30°C, and the inorganic solids were filtered and washed with toluene (50 mL). The filtrate was collected and concentrated under reduced pressure, followed by flash column chromatography (ethyl acetate as the eluent) to give 10.74 g of an off-white solid in 82.5% yield.

[0059] 1 H-NMR (400MHz, CDCl 3 )δ: 0....

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Abstract

The invention belongs to the field of medicines, and relates to a benzofuran derivative as well as a preparation method and application thereof. The structural formula of the benzofuran derivative is shown as a formula I. Pharmacological research shows that the compound prepared by the invention can effectively inhibit the activity of AKT protein kinase, and can be used as an AKT protein kinase inhibitor to effectively prevent and / or treat hyperproliferative diseases such as cancers.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to a benzofuran derivative as well as a preparation method and application thereof. Background technique [0002] At present, malignant tumor is one of the diseases with the highest fatality rate in the world, second only to cardiovascular and cerebrovascular diseases. Therefore, the research and development of anticancer drugs has very important clinical and social significance. Studies have shown that protein kinase signaling pathways play an important role in the formation of cancer. The phosphatidylinositol 3 kinase / protein kinase B / mammalian target of rapamycin (PI3K / Akt / mTOR) signaling pathway is one of the important signaling pathways in mammalian cells. The activation state of the molecule plays the role of inhibiting cell apoptosis and promoting proliferation. It can be seen that this pathway is overactivated in cancer patients and is one of the most frequently altered pathways in hu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D493/04A61P35/00A61P29/00
Inventor 苏聪高磊
Owner 苏聪
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