Pyrimidine-2,4-diamine derivative and anticancer pharmaceutical composition comprising same as effective ingredient

一种药学、化合物的技术，应用在癌症的预防或治疗用药学组合物领域，达到防止癌症复发、优秀抑制间变性淋巴瘤激酶活性的效果

Active Publication Date: 2017-02-22
KOREA RES INST OF CHEM TECH
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Then, drugs that exhibit anticancer effects as tyrosine kinase inhibitors include epidermal growth factor receptor (EGFR, epidermal growth factor receptor) used as a therapeutic agent for non-small cell lung cancer, and Gemfid as a tyrosine kinase inhibitor. Gefitinib and erlotinib, sorafenib and sunitinib are used as therapeutic agents for renal cell carcinoma, but are known to have bleeding, cardiac paralysis, heart failure, liver Side effects such as functional failure

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
  • Pyrimidine-2,4-diamine derivative and anticancer pharmaceutical composition comprising same as effective ingredient
  • Pyrimidine-2,4-diamine derivative and anticancer pharmaceutical composition comprising same as effective ingredient
  • Pyrimidine-2,4-diamine derivative and anticancer pharmaceutical composition comprising same as effective ingredient

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0182]And, the present invention provides the preparation method of the compound represented by above-mentioned chemical formula 1, as shown in following reaction formula 1, the preparation method of above-mentioned compound comprises: Step 1, make the compound represented by chemical formula 2 and the compound represented by chemical formula 3 react to prepare the compound represented by Chemical Formula 4; Step 2, to prepare the compound represented by Chemical Formula 5 by replacing the -Boc group of the compound represented by Chemical Formula 4 obtained in the above Step 1 with hydrogen; and Step 3, making the compound represented by the Chemical Formula 5 in the above Step 2 The compound represented by Chemical Formula 5 obtained in and the compound represented by Chemical Formula 6 were reacted to obtain the compound represented by Chemical Formula 1.

[0183] Reaction 1:

[0184]

[0185] In the above reaction formula 1, -Boc is or R 1 , R 2 , R 3 , R 4 , R ...

preparation example 1

[0274] Preparation of tert-butyl-6-amino-7-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

[0275] Step 1: Preparation of 2,2,2-trifluoro-N-(4-methoxyphenylethyl)acetamide

[0276]

[0277] After dissolving 4-methoxyphenylethylamine (12.0 g, 79.4 mmol) in dichloromethane, trifluoroacetic acid anhydrate (13.5 mL, 95.2 mmol) was added.

[0278] The temperature was lowered to 0°C, triethylamine (27.6 mL, 198 mmol) was slowly added, and stirred at room temperature for 3 hours. After completion of the reaction, water was added for dilution, extracted twice with ethyl acetate, dried over anhydrous magnesium sulfate, and then concentrated under pressure. The filtrate which was concentrated under pressure was purified by column chromatography, and the target compound (19 g, 97%) was obtained.

[0279] 1H-NMR (300MHz, DMSO-d 6 )δ2.72(t, J=7.2Hz, 2H), 3.35-3.39(m, 2H), 3.71(s, 3H), 6.87(d, J=8.4Hz, 2H), 7.11(d, J=8.7 Hz, 2H), 9.46(s, 1H);

[0280] LC / MS 248.30[M + +H].

[...

preparation example 2

[0306] Preparation of tert-butyl-7-amino-6-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

[0307] Step 1: Preparation of methyl 3-methoxyphenylethyl carbamate

[0308]

[0309] After dissolving 3-methoxyphenylethylamine (30.0 g, 198 mmol) in dichloromethane, sodium carbonate (42.1 g, 396 mmol) was added. Methyl chloroformate (18.6 mL, 238 mmol) was added slowly at a temperature of 0°C and stirred for 2 hours. After completing the reaction, the organic layer was separated by adding water, and dried over anhydrous magnesium sulfate. Concentration under pressure was performed to obtain the target compound (35 g, 86%).

[0310] 1H NMR (300MHz, CDCl 3 )δ2.76(t, J=6.9Hz, 2H), 3.41(t, J=6.9Hz, 2H), 3.66(s, 3H), 3.80(s, 3H), 3.92(s, 3H), 4.69( br s, 1H), 6.74-6.79(m, 3H), 7.20-7.26(m, 1H);

[0311] EI / MS 209.1 [M+].

[0312] Step 2: Preparation of 6-methoxy-3,4-dihydroisoquinolin-1(2H)-one

[0313]

[0314] Polyphosphoric acid (184mL, 184mmol) was put into the reacti...

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 present invention relates to a pyrimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for prevention or treatment of cancer comprising the same as an effective ingredient. A compound according to the present invention has the good effect of inhibiting anaplastic lymphoma kinase (ALK) activity, whereby a therapeutic effect on cancer cells having a anaplastic lymphoma kinase (ALK) fusion protein such as EML4-ALK, NPM-ALK, etc. can be enhanced and it is expected that a recurrence of cancer will be effectively inhibited. As such, the compound can be effectively used in a pharmaceutical composition for prevention or treatment of cancer.

Description

technical field [0001] The present invention relates to a pyrimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for preventing or treating cancer comprising the same as an active ingredient. Background technique [0002] Unlike normal cells, which can proliferate and suppress in a regular and controlled manner according to individual needs, cancers are cell clusters formed of undifferentiated cells that proliferate indefinitely regardless of the desired state in tissues. called a tumor. Cancer cells undergoing such unrestricted proliferation infiltrate the surrounding tissue, and in the case of further deterioration, the above-mentioned cancer cells metastasize to other organs of the body, accompanied by severe pain, and eventually called an intractable disease leading to death. [0003] According to the data of the American Cancer Society (American Cancer Society), in 2007, there were more than 12 million patients...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/12C07D471/04A61K31/506A61P35/00
CPCC07D403/12C07D471/04A61K31/506A61P35/00A61P43/00C07D401/12C07D401/14C07D405/14C07D209/04C07D239/12
Inventor 尹昌洙金亨来赵成伦郑熙静李光浩蔡钟学李廷玉朴志勋金珌虎黄宗渊河在斗安璇珠
Owner KOREA RES INST OF CHEM 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