Diarylurea derivatives and application thereof used for preparing anti-neoplastic medicament

A technology of derivatives and heteroaryl groups, which can be used in anti-tumor drugs, drug combinations, medical preparations containing active ingredients, etc., and can solve problems such as insufficient inhibition of tumor development.

Inactive Publication Date: 2009-10-07
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] With the in-depth study of the mechanism of tumorigenesis, it is found that the signal transduction of solid tumors is a complex, mu

Method used

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  • Diarylurea derivatives and application thereof used for preparing anti-neoplastic medicament
  • Diarylurea derivatives and application thereof used for preparing anti-neoplastic medicament
  • Diarylurea derivatives and application thereof used for preparing anti-neoplastic medicament

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0102] Example 1: 1-[4-[(8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)methoxy]phenyl]-3-(2 , 6-difluorophenyl) urea methanesulfonate;

[0103] Step A: Preparation of 2-chloromethyl-8-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

[0104] Add 38g (0.35mol) of 2-amino-4-picoline and 250g of polyphosphoric acid into a 1000ml three-necked flask, and heat to 45°C. Under stirring, 55 ml (0.43 mol) of ethyl 4-chloroacetoacetate was added dropwise, and after the drop was completed, the temperature was raised to 125° C. for about 2 hours. Cool to 50°C after the reaction is complete, then pour into a large amount of ice water, CHCl 3 Extract, wash with water, and dry over anhydrous sodium sulfate. Evaporate to dryness to obtain 60.0 g of off-white solid, yield: 81.4%, MS: 209 (M+1).

[0105] Step B: Preparation of 8-methyl-2-[(4-nitrophenoxy)methyl]-4H-pyrido[1,2-a]pyrimidin-4-one

[0106] Dissolve 27g (0.129mol) of 2-chloromethyl-8-methyl-4H-pyrido[1,2-a]pyrimidin-4-one in 200ml of DMF,...

Embodiment 2

[0115] 1-[4-[(8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)methoxy]phenyl]-3-(2,4-di Methylphenyl)urea methanesulfonate;

[0116] MS: 429(M+1)

[0117] 1 H-NMR (DMSO-d 6 )δ(ppm): 8.98(s, 1H), 8.89(s, 1H), 7.85(s, 1H), 7.68(s, 1H), 7.61(s, 1H), 7.48(s, 1H), 7.42( s, 2H), 6.96~7.01 (t, J 1 =9Hz,J 2 =6.6Hz, 4H), 6.55(s, 1H), 5.13(s, 2H), 2.57(s, 3H), 2.20(s, 3H), 2.18(s, 3H).

Embodiment 3

[0119] 1-[4-[(4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)methoxy]phenyl]-3-(2,4-dimethylphenyl) Urea mesylate;

[0120] MS: 415(M+1);

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Abstract

The invention belongs to the field of medical technology, which relates to diarylurea derivatives or salts accepted in medicine shown in formula I, wherein substituents of Ar1, Ar2, X and n have definitions given in an instruction. The derivatives shown in the formula I can be used for preparing receptor protein-tyrosine kinase inhibitor (RPTKI), and medicaments used for treating and/or preventingcancer or other proliferative diseases. The derivatives or salts accepted in medicine can be taken as active ingredients for preparing composition or different preparations used in clinical requirement mixed together with different carriers or excipient in medicine so as to be used for treating and/or preventing from various cancers.

Description

technical field [0001] The invention belongs to the technical field of medicine, relates to bisaryl urea derivatives and their use in the preparation of antitumor drugs, and also relates to pharmaceutical compositions using the derivatives as active ingredients, and their use in the preparation of receptor protein tyrosine Kinase inhibitors, and use in medicaments for the treatment and / or prevention of various cancers and proliferative diseases. Background technique [0002] Cancer generally refers to all malignant tumors and is a common and frequently-occurring disease that seriously threatens human life. According to WHO statistics, there are about 9 million new cases of malignant tumors in the world every year. By 2015, the number of newly discovered malignant cases worldwide will reach 15 million per year, and cancer will become the number one killer of human health by then. [0003] With the in-depth study of the mechanism of tumorigenesis, it is found that the signal...

Claims

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Application Information

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IPC IPC(8): C07D471/04A61K31/519A61P35/00
Inventor 宫平刘亚婧赵燕芳翟鑫
Owner SHENYANG PHARMA UNIVERSITY
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