Novel inhibitor of epidermal growth factor receptor (EGFR) and application thereof

An epidermal growth factor and inhibitor technology, which can be used in medical preparations containing active ingredients, organic active ingredients, organic chemistry, etc., to solve problems such as hormone resistance, rapid metastasis, and resistance to radiotherapy and chemotherapy.

Inactive Publication Date: 2012-02-29
EAST CHINA UNIV OF SCI & TECH
View PDF2 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Overexpression of EGFR often indicates poor prognosis, rapid metastasis, resis

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Novel inhibitor of epidermal growth factor receptor (EGFR) and application thereof
  • Novel inhibitor of epidermal growth factor receptor (EGFR) and application thereof
  • Novel inhibitor of epidermal growth factor receptor (EGFR) and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] 3-(1,1,3,3-Tetramethylbutylamino)-6-chloroimidazo[1,2-a]pyrazine

[0029] Under nitrogen protection, add 100 mL of a mixture of ethanol and dichloromethane and 2-amino-5-chloropyrazine (2.00 g, 15 mmol) into a 150 mL three-necked flask, stir and dissolve, then add formaldehyde (5.33, 75 mmol) and trifluoromethane Scandium sulfonate (0.74 g, 1.5 mmol). Stir at room temperature for 1 h. Add 1,1,3,3-tetramethylbutylisonitrile (2.33 g, 15 mmol) and stir at room temperature for 48 h. TLC showed that the raw material was completely reacted, the solvent was distilled off under reduced pressure, the residue was separated with water (100 mL) and ethyl acetate (150 mL), the organic layer was dried over anhydrous sodium sulfate, and concentrated to obtain the product (2.10 g, crude product). It was directly used in the next reaction without purification.

[0030] MS (EI) m / z (%): 280.2 (100%), 282.2 (33%) 1 H NMR (DMSO-d 6 , 400MHz) δ: 8.71(s, 1H), δ: 8.46(s, 1H), δ: 7.52(s, ...

Embodiment 2

[0032] 3-Amino-6-chloroimidazo[1,2-a]pyrazine

[0033] In a 250mL round bottom flask, add 3-(1,1,3,3-tetramethylbutylamino)-6-chloroimidazo[1,2-a]pyrazine (1.00g, 3.6mmol) and dry After dissolving dichloromethane (45 mL), trifluoroacetic acid (100 mL) was added under ice-cooling, and stirred at room temperature for 1 h. After the reaction, the solvent was distilled off under reduced pressure, and saturated NaHCO 3 (200mL) after solution treatment, dichloromethane (200mL) extraction, after the organic layer is dried over anhydrous sodium sulfate, dichloromethane solvent is removed, and crude product is purified by column chromatography to obtain white solid 3-amino-6-chloroimidazo[1 , 2-a]pyrazine (0.30 g, 50%).

[0034] MS (EI) m / z (%): 168.0 (100%), 170.0 (33%) 1 H NMR (DMSO-d 6 , 400MHz) δ: 8.62(s, 1H), δ: 8.35(s, 1H), δ: 7.20(s, 1H), δ: 6.84(s, 2H)

Embodiment 3

[0036]3-(3-Chloro-4-fluorobenzylamino)-6-chloroimidazo[1,2-a]pyrazine

[0037] Add 3-amino-6-chloroimidazo[1,2-a]pyrazine (0.20g, 1.2mmol) in a 25mL round bottom flask, (3-chloro-4-fluoroben bromide (0.40g, 1.8mmol) and 10mL of dioxane, heated and stirred under reflux for 3h. After the reaction, the solvent was distilled off, and 100mL of ethyl acetate was added. After dissolving, the solution was washed with saturated NaHCO 3 (100mL) solution was washed, dried over anhydrous sodium sulfate, and purified by column chromatography to obtain white solid 3-(3-chloro-4-fluorobenzylamino)-6-chloroimidazo[1,2- a] Pyrazine (0.28 g, 75%).

[0038] MS (EI) m / z (%): 310.0 (100%), 312.0 (65%) 1 H NMR (DMSO-d 6 , 400MHz) δ: 8.72(s, 1H), δ: 8.45(s, 1H), δ: 7.10-6.79(m, 4H), δ: 6.68(t, 1H), δ: 4.29(d, 2H)

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a novel inhibitor of an EGFR and an application thereof. The general formula of the EGFR inhibitor is represented by a formula shown in the specification. In the formula, L is a C1-4 lower alkyl group, a C1-4 lower alkyloxy group, a C1-4 lower alkylamino group, O, OR4, S, SR4, NH or NR4, wherein R4 is a C1-4 lower alkyl group, a C1-4 lower alkyloxy group, or a C1-4 lower monoalkylamino group; R1 is a phenyl group, a substituted phenyl group, a substituted five-nine-membered aromatic cycle, a substituted five-nine-membered aromatic heterocycle or a substituted aromatic bicycle; R2 is hydrogen, a C1-9 alkyl group, a C1-9 alkyloxy group, OH, NH2, NO2, SH, or NR5R6, wherein R5R6 is hydrogen, a C1-9 alkyl group, a C1-9 alkyloxy group or a C1-9 monoalkylamino group, a three-nine-membered substituted aliphatic cycle, an aliphatic heterocycle, a substituted aromatic cycle, a substituted aromatic heterocycle, or a three-nine-membred bicycle; and R3 is halogen, H, SH, OH or NO2. The virtual screening of a computer, EGFR kinase activity inhibition experiments, and cancer cell inhibition experiments confirm that compounds of above formula are the EGFR inhibitor and have good curative effects and prevention effects on cancers related with the EGFR.

Description

【Technical field】 [0001] The invention relates to the technical field of inhibiting epidermal factor receptor and related receptors, in particular, a novel inhibitor of epidermal growth factor receptor and its application. 【Background technique】 [0002] Epidermal growth factor receptor (EGFR) is an important transmembrane tyrosine kinase growth factor receptor, located in the cell membrane, and HER2 / ErbB-2 / Neu / pl85, HER3 / ErbB-3, HER4 / ErbB-4 Equivalently belong to the HER / ErbB family. It consists of three parts: extracellular region, transmembrane region and intracellular region. Its ligands include epidermal growth factor (epidermal growth factor, EGF), transforming growth factor-alpha (transforming growth factor-alpha, TGF-alpha), beta-cellulin (betacellulin, BTC), amphiregulin (amphiregulin), epidermin (epiregulin), heparin-binding epidermal growth factor (heparin-binding EGF, HB-EGF), etc. EGF and TGF-α are the most important. EGFR interacts with its ligand extracellu...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D487/04A61K31/4985A61P35/00
Inventor 蓝闽波李思远唐赟赵红莉袁慧慧孙宪强郭春莹洪涛杨福科
Owner EAST CHINA UNIV OF SCI & TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap