Quinazoline derivative serving as EGFR inhibitor and application of derivative

A drug and compound technology, applied in the field of biomedicine, can solve the problems of drug resistance and poor selectivity of EGFR inhibitors

Inactive Publication Date: 2019-05-21
WUHAN DENUOMEI BIOLOGY MEDICINE TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the second-generation inhibitors have solved the problem of drug resistance to a certain extent, due to their high inhibition of wild-type EGFR, side effects such as diarrhea and rash
[0006] In order to solve the defects of e

Method used

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  • Quinazoline derivative serving as EGFR inhibitor and application of derivative
  • Quinazoline derivative serving as EGFR inhibitor and application of derivative
  • Quinazoline derivative serving as EGFR inhibitor and application of derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] The preparation of embodiment 1 compound I-a

[0081]

[0082] first step:

[0083] Compound shown in formula I-a-1 (1.46g, 5.77mmol) was dissolved in 60mL isopropanol, compound (840mg, 5.77mmol) and p-toluenesulfonic acid (993mg, 5.77mmol) shown in formula 2 were added thereto, and The mixture was stirred and reacted at 75°C for 5 hours. After the reaction was detected by TLC, the solvent was evaporated under reduced pressure, and the residual solid was dispersed in 200 mL of ethyl acetate, washed with saturated aqueous sodium bicarbonate, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure A crude product was obtained, which was separated by column chromatography to obtain the compound shown in formula I-a-3 (yield 1.59 g, yield 76%).

[0084] Step two:

[0085] The compound shown in formula I-a-3 (290 mg, 0.8 mmol) was placed in a 100 mL hydrogenation bottle, 50 mL of methanol was added, and after nitrogen rep...

Embodiment 2

[0092] The preparation of embodiment 2 compound I-b

[0093]

[0094] The preparation method of compound I-b was carried out in a manner similar to that of Example 1, except that the starting materials were changed to compound I-b-1 and compound I-b-7. Purification by silica gel chromatography gave the compound represented by formula I-b (yield 66%, HPLC purity 99.6%).

[0095] m / z:530(M+H) + .

Embodiment 3

[0096] The preparation of embodiment 3 compound I-c

[0097]

[0098] The preparation method of compound I-c was experimented in a manner similar to that of Example 1, except that the starting material was changed to compound I-c-7. Purification by silica gel chromatography gave the compound represented by formula I-c (yield 52%, HPLC purity 99.2%).

[0099] m / z:502(M+H) + .

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PUM

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Abstract

The invention discloses a quinazoline derivative serving as an EGFR inhibitor and application of the derivative. The quinazoline derivative is a compound shown in formula I and is pharmaceutically acceptable salts or prodrugs. The compound can be used for being prepared into drugs for treating and/or preventing cancers, wherein the formula I is shown in the description.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to quinazoline derivatives as EGFR inhibitors and applications thereof. Background technique [0002] Malignant tumor is a common and frequently-occurring disease that seriously threatens human health. It is caused by abnormal proliferation of cells in the human body. Lung cancer, gastrointestinal cancer and liver cancer are the most common tumors in men, accounting for more than 70% of all cases (lung cancer 23%, gastric cancer 15.2%, liver cancer 13.57%, esophageal cancer 10.46%, colorectal cancer 9.39%), while breast cancer, Lung cancer, gastrointestinal cancer and liver cancer are the most common tumors in women, accounting for more than 60% of all cases (breast cancer 16.97%, lung cancer 14.85%, colorectal cancer 9.68%, gastric cancer 8.53%, liver cancer 6.17%). With the aging population in China, the prevalence of cancer is bound to increase. In addition, environmental pol...

Claims

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Application Information

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IPC IPC(8): C07D239/94C07D401/12C07D405/12A61P35/00A61K31/517A61K31/5377
Inventor 邱启裕全欣鑫
Owner WUHAN DENUOMEI BIOLOGY MEDICINE TECH
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