Hydroximic acid-containing 2-phenylaminopyrimidine derivatives and application thereof

A technology of anilinopyrimidine and hydroxamic acid, which is applied to 2-phenylaminopyrimidine derivatives and in the fields of tumor treatment and medicinal chemistry, can solve the problems of large toxic and side effects, difficulty in suppressing tumor development, and easy generation of drug resistance.

Active Publication Date: 2022-03-01
THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, most of the anti-tumor drugs in clinical use are cytotoxic drugs, which have many problems such as high toxicity and side effects, and are prone to drug resistance. However, although the highly selective anti-tumor drugs that act on a single target on the market in recent years

Method used

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  • Hydroximic acid-containing 2-phenylaminopyrimidine derivatives and application thereof
  • Hydroximic acid-containing 2-phenylaminopyrimidine derivatives and application thereof
  • Hydroximic acid-containing 2-phenylaminopyrimidine derivatives and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: 2-Chloro-4-((trimethylsilyl)ethynyl)pyrimidine (2a)

[0035]

[0036] Triphenylphosphine palladium dichloride (Pd(PPh 3 ) 2 Cl 2 , 0.047g, 0.067mmol), triphenylphosphine (PPh 3 , 0.034g, 0.13mmol), 2,4-dichloropyrimidine (2.0g, 13.4mmol) were added to tetrahydrofuran (THF, 10mL) and triethylamine (Et 3 N, 15 mL) in a mixed solvent, the air in the reaction system was replaced with nitrogen, and then copper iodide (CuI, 0.026 g, 0.13 mmol) and trimethylsilylacetylene (1.579 g, 16.1 mmol) were added in sequence. Cool to room temperature after heating to reflux reaction 3h, filter and remove the solid (Et 3 N . HCl), the filtrate was concentrated, and purified by column chromatography (petroleum ether: ethyl acetate=100:1, volume ratio) to obtain a yellow solid, namely 2-chloro-4-((trimethylsilyl)ethynyl)pyrimidine ( 2a), yield: 57%.

Embodiment 2

[0037] Example 2: 2-Chloro-5-fluoro-4-((trimethylsilyl)ethynyl)pyrimidine (2b)

[0038]

[0039] The preparation method refers to Example 1, wherein 2,4-dichloropyrimidine is replaced by 2,4-dichloro-5-fluoropyrimidine, and the reaction time is 10 minutes. Yellow solid (2b), yield: 62%. 1 H NMR (400MHz, CDCl 3 )δ8.50(s,1H),0.31(s,9H).ESI-MS m / z:229.0[M+H] + .

Embodiment 3

[0040] Example 3: 2-Chloro-4-ethynylpyrimidine (3a)

[0041]

[0042]2-Chloro-4-((trimethylsilyl)ethynyl)pyrimidine (2a, 1.0 g) was dissolved in 10 mL of methanol (MeOH). The KOH solution prepared by dissolving potassium hydroxide (KOH, 3 mg) in 5 mL of methanol was added to the above reaction system, reacted at room temperature for 0.5 h, concentrated and purified by column chromatography (eluted with pure dichloromethane) to obtain a white solid (3a), Yield: 90%.

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PUM

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Abstract

The invention belongs to the field of medicinal chemistry, and particularly relates to 4-triazole-2-phenylaminopyrimidine derivatives of which the structures are shown in the specification. In the formula (I), R1 is methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; r2 is hydrogen, fluorine or trifluoromethyl; x is oxygen or. Pharmacological experiments show that the compounds and pharmaceutically acceptable salts thereof have the effect of inhibiting tumor cell proliferation.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a class of 2-anilinopyrimidine derivatives containing hydroxamic acid and its application in the field of tumor treatment. Background technique [0002] Tumor is one of the major refractory diseases that seriously threaten human life and health. In our country, malignant tumor has become the first cause of death among residents. Although antitumor drugs, as an important means of tumor treatment, play a very important role in the clinical treatment of tumor patients, however. At present, most of the anti-tumor drugs in clinical use are cytotoxic drugs, which have many problems such as high toxicity and side effects, and are prone to drug resistance. However, although the highly selective anti-tumor drugs that act on a single target on the market in recent years have a clear mechanism of action, they are not It is still difficult to curb the development of tumors. ...

Claims

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Application Information

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IPC IPC(8): C07D403/04A61P35/00A61K31/506
CPCC07D403/04A61P35/00
Inventor 阚全程田鑫王素华程伟彦杜玥
Owner THE FIRST AFFILIATED HOSPITAL OF ZHENGZHOU UNIV
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