Pyrimidine-2,4-diamine derivative and pharmaceutical anticancer composition containing same as active ingredient

A kind of technology of diamine derivative and pyrimidine, which is applied in the field of pharmaceutical compositions for preventing or treating cancer, and achieves the effect of improving the therapeutic effect

Active Publication Date: 2016-10-12
KOREA RES INST OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these drugs show side effects such as bleeding, heart attack, heart failure, and liver failure

Method used

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  • Pyrimidine-2,4-diamine derivative and pharmaceutical anticancer composition containing same as active ingredient
  • Pyrimidine-2,4-diamine derivative and pharmaceutical anticancer composition containing same as active ingredient
  • Pyrimidine-2,4-diamine derivative and pharmaceutical anticancer composition containing same as active ingredient

Examples

Experimental program
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preparation example Construction

[0106] In the preparation method of the present invention, step 1 is to obtain the compound represented by formula 4 by reacting the compound represented by formula 2 with the compound represented by formula 3.

[0107] Specifically, the compound represented by Formula 4 is prepared by reacting the compound represented by Formula 2 with the compound represented by Formula 3 via alkylation in the presence of an organic solvent and a base.

[0108] At this time, the organic solvent used herein is selected from the group consisting of tetrahydrofuran; dioxane; ether solvents including diethyl ether and 1,2-dimethoxyethane; lower alcohols including methanol, ethanol , propanol and butanol; dimethylformamide (DMF), dimethylsulfoxide (DMSO), Tosylate, Chlorobenzenesulfonate, Xylenesulfonate, Phenylacetate, Phenylpropionate, Phenylbutyrate, Citrate, Lactate, Beta-Hydroxybutyrate, Glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2...

Embodiment 1

[0129] Example 1: 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(1,2,3,6-tetrahydropyridine-4- Preparation of yl)phenyl)pyrimidine-2,4-diamine

[0130] Step 1: 4-(4-((5-Chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-3-methoxyphenyl)- Preparation of tert-butyl 5,6-dihydropyridine-1(2H)-carboxylate

[0131]

[0132] 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine (1.6g, 4.6mmol) was dissolved in 25ml of THF, and 4-(4- Amino-3-methoxyphenyl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (1.4 g, 4.6 mmol). Add 4,5-bisdiphenylphosphine-9,9-dimethylxanthene to it in sequence (266mg, 0.46mmol) and Cs 2 CO 3 (4.5 g, 13.8 mmol), followed by degassing by filling with nitrogen. Add Pd(OAc) to it 2 (51.6 mg, 0.23 mmol). After filling with nitrogen, the reaction mixture was stirred at 130 °C for 18 hours. After the reaction was complete, the mixture was then washed with EA / H 2 O extraction. The organic layer was wash...

Embodiment 2

[0138] Example 2: 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2 Preparation of -(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine

[0139] Step 1: 4-(4-((5-Chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2- Preparation of tert-butyl methylphenyl)-5,6-dihydropyridine-1(2H)-carboxylate

[0140]

[0141] 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine (1 g, 2.88 mmol) was dissolved in 20 ml of THF, and 4-(4-amino - tert-butyl 5-isopropoxy-2-methylphenyl)-5,6-dihydropyridine-1(2H)-carboxylate (955 mg, 2.88 mmol). Add 4,5-bisdiphenylphosphine-9,9-dimethylxanthene (167 mg, 0.288 mmol) and Cs in sequence 2 CO 3 (2.8 g, 8.64 mmol), followed by degassing by filling with nitrogen. Add Pd(OAc) to it 2 (32 mg, 0.144 mmol). After filling with nitrogen, the reaction mixture was stirred at 130 °C for 18 hours. After the reaction was complete, the mixture was then washed with EA / H 2 O extraction. Th...

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Abstract

The present invention relates to a pyrimidine-2,4-diamine derivative or pharmaceutically acceptable salts thereof, and a pharmaceutical composition for preventing or treating cancer, which contains a pyrimidine-2,4-diamine derivative as an active ingredient. A compound according to the present invention is very effective in suppressing anaplastic lymphoma kinase (ALK) activity, and as a result, can improve the effectiveness of treatment on cancer cells having anaplastic lymphoma kinase (ALK) fusion proteins, such as EML4-ALK and NPM-ALK, and is expected to effectively prevent recurrence of cancer, thus being useful as a composition for preventing or treating 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 containing the pyrimidine-2,4-diamine derivative as an active ingredient for preventing or treating cancer. Background technique [0002] Unlike normal cells that proliferate or inhibit according to certain rules and necessary methods, cancer cells proliferate infinitely in tissues regardless of these necessary rules and methods. Cancer is a cell mass composed of such infinitely proliferating undifferentiated cells, which also called a tumor. Unrestricted proliferation of cancer cells invades surrounding tissues and even other organs, causing severe pain and problems, and even death. Therefore, cancer is considered an incurable disease. [0003] According to the report of the American Cancer Society, there were at least 12 million new patients diagnosed with cancer worldwide in 2007, of which 7.6 million ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12A61K31/506A61P35/00
CPCA61K31/506A61P35/00C07D401/12
Inventor 郑熙静金亨来金珌虎朴志勋安璇珠尹昌洙李光浩李廷玉赵成伦蔡锺学河在斗黄宗渊
Owner KOREA RES INST OF CHEM TECH
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