Kinase inhibitor and application thereof

A technology of medicinal salts and solvates, which is applied in the application field of compounds and drugs as ALK inhibitors, and can solve the problems of drug resistance and other problems

Active Publication Date: 2015-11-25
HUBEI BIO PHARMA IND TECHCAL INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although people have studied a large number of compounds with inhibitory activity on protein kinases, and some protein kinase ...

Method used

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  • Kinase inhibitor and application thereof
  • Kinase inhibitor and application thereof
  • Kinase inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Embodiment 1: compound (intermediate) shown in preparation formula 2-a

[0070]

[0071] Put the compound shown in formula a (15g, 106.31mmol), potassium carbonate (29.38g, 212.61mmol) in a 500mL round bottom bottle, add 150ml of DMF, add isopropyl mercaptan (compound shown in formula b) under stirring (8.5g, 111.62mmol), the mixture was stirred and heated to 80°C, and reacted for 5 hours. After the reaction was completed, the reaction solvent was evaporated under reduced pressure, and the obtained crude product was washed with water, extracted with ethyl acetate, dried, concentrated, and obtained by column chromatography. The compound shown in c (yield 19.5 g, yield 95%).

[0072]The compound shown in formula c (19.5g, 98.86mmol) and m-chloroperoxybenzoic acid (mCPBA, the compound shown in formula d) (60.2g, 348.84mmol) were placed in a 1000mL round bottom bottle, and 500ml of dichloromethane was added , the mixture was stirred overnight at room temperature, quench...

Embodiment 2

[0074] Embodiment 2: compound (intermediate) shown in preparation formula 2-b

[0075]

[0076] Compound shown in formula f (14.2g, 0.1mol), potassium carbonate (27.6g, 0.2mol) are placed in 500mL round bottom bottle, add 150 milliliters of DMF, add isopropyl thiol (compound shown in formula b) under stirring ) (8.0g, 0.105mol), the mixture was stirred and heated to 75°C, reacted for 6 hours, after the reaction was completed, the reaction solvent was evaporated under reduced pressure, the obtained crude product was washed with water, extracted with ethyl acetate, dried and concentrated, and obtained by column chromatography Compound represented by formula g (yield: 17.9 g, yield: 92.5%).

[0077] The compound shown in formula g (19.8g, 0.1mol) and m-chloroperoxybenzoic acid (mCPBA, the compound shown in formula d) (60.9g, 0.35mol) were placed in a 1000mL round bottom bottle, and 500ml of dichloromethane was added , the mixture was stirred overnight at room temperature, que...

Embodiment 3

[0079] Embodiment 3: compound (intermediate) shown in preparation formula 2-b

[0080]

[0081] Compound (15.9g, 0.1mmol) shown in formula j, potassium carbonate (27.6g, 0.2mmol) are placed in 500mL round bottom bottle, add 150 milliliters of DMF, add isopropyl mercaptan under stirring (compound shown in formula b ) (8.0g, 0.105mol), the mixture was stirred and heated to 80°C, reacted for 5 hours, after the reaction was completed, the reaction solvent was evaporated under reduced pressure, the obtained crude product was washed with water, extracted with ethyl acetate, dried and concentrated, and obtained by column chromatography Compound represented by formula g (yield: 18.1 g, yield: 93%).

[0082] The compound shown in formula g (19.8g, 0.1mol) and m-chloroperoxybenzoic acid (mCPBA, the compound shown in formula d) (48.7g, 0.28mol) were placed in a 1000mL round bottom bottle, and 500ml of dichloromethane was added , the mixture was stirred overnight at room temperature, ...

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PUM

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Abstract

The invention provides a kinase inhibitor and application thereof. The compound is a compound shown in a formula I or pharmaceutical salt, a hydrate, a solvate, a metabolite or a prodrug of the compound shown in the formula I, wherein R1 and R2 are defined in the description. The compound and a pharmaceutical composition can be used for preparing an ALK inhibitor and drugs for treating or preventing cancers and inhibiting the proliferative effect of cancer cells. The formula I is shown in the description.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to novel compounds as kinase inhibitors, specifically, the invention relates to compounds as ALK inhibitors, and the application of these compounds in the preparation of medicines for treating and preventing cancer. Background technique [0002] Non-small-cell lung cancer (NSCLC) is synonymous with "non-small-cell carcinoma". Non-small cell lung cancer, including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, has slower growth and division of cancer cells than small cell carcinoma, and relatively late spread and metastasis. Non-small cell lung cancer accounts for about 80-85% of all lung cancers. Statistics show that the current incidence of lung cancer in my country is increasing by 26.9% every year. From 2000 to 2005, the number of lung cancer patients in China is estimated to increase by 120,000 people. Among them, male lung cancer patients increased from 260,000 in 20...

Claims

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Application Information

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IPC IPC(8): C07D401/12C07D409/12C07D239/48A61K31/506A61P35/00
CPCA61K31/506C07D239/48C07D401/12C07D409/12
Inventor 王学海许勇李莉娥盛锡军黄璐张晓林乐洋黄文杰
Owner HUBEI BIO PHARMA IND TECHCAL INST
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