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2,4,6-trisubstituted pyrimidine compounds containing 1,2,3-triazole, preparation method and application thereof

A compound, tri-substituted technology, applied in the application field of anti-tumor drug lead compounds

Active Publication Date: 2014-06-25
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few reports on the combination of the two, so this study has very important value

Method used

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  • 2,4,6-trisubstituted pyrimidine compounds containing 1,2,3-triazole, preparation method and application thereof
  • 2,4,6-trisubstituted pyrimidine compounds containing 1,2,3-triazole, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0059] general formula( II ) is prepared with reference to the following documents:

[0060] H.I. Skulnick, J.H. Ludens, M.G. Wendling. Journal of Medicinal Chemistry , 1986 , 29, 1499-1504.

[0061] general formula( IV ) is prepared with reference to the following documents:

[0062] (a) Ina Wilkening.; Giuseppe del Signore.; C. P. R. Hackenberger. Chem. Commun. 2011 , 47, 349-351. (b) Mingyu Hu.; Junqi Li.; ShaoQ Yao. Org. Lett , 2008 , 10, 5529-5531.

Embodiment

[0063] Example 1 general formula( II ), R 3 =H, the derivative of ( II-1 ) preparation

[0064] Add ethyl cyanoacetate (2.262g, 20mmol) and sodium hydroxide (1.200g, 30mmol) into the ethanol solution, under reflux conditions, react for a period of time, then add thiourea (2.284g, 30mmol) and benzaldehyde (3.184 g, 30mmol) was added into the reaction system, stirred and reacted, followed by TLC detection. After the reaction, filter with suction and recrystallize to obtain the pure product.

[0065] Example 2 general formula( III ), R 3 = H, a derivative of ( III-1 ) preparation

[0066] Add propyne bromide (3.569g, 30mmol) dropwise into a solution of II-1 (2.674g, 10mmol) in 1,4-dioxane, heat and stir to react. Monitor the reaction process with TLC until the reaction is complete; then directly dropwise add phosphorus oxychloride (4.600g, 30mmol) in the reaction system, after the reaction is complete, pour it into ice water, stir, solids are precipitated, and su...

Embodiment 32

[0139] Example 32 The antitumor activity assay of above-mentioned compound:

[0140] 1. Experimental method:

[0141] The compounds used in the screening are all synthesized and purified by the present invention; sample stock solution: weigh 3-5 mg of the sample and place it in a 1.5 mL EP tube, and then use DMSO to prepare a concentration of 128×10 3 μg / mL solution, stored at 4 °C, and diluted with medium according to the required concentration during the experiment.

[0142] 2. Primary screening

[0143] Take the cells in the logarithmic growth phase, digest and count them, adjust the cell density with medium, inoculate 4000-5000 cells / well into a 96-well plate, 150 μL per well, culture for 24 h, discard the medium, add Drugs (50 μg / mL, 100 μg / mL) diluted with culture medium were used, and 6 replicate wells were set up for each concentration, and a blank control group and a negative control group were also set up. After 72 h of drug action, add 20 μL MTT to ea...

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Abstract

The invention discloses 2,4,6-trisubstituted pyrimidine compounds containing 1,2,3-triazole, a preparation method and application thereof in preparation of medicine and belongs to the field of medicinal chemistry. A pyrimidine parent nucleus and a 1,2,3-triazole activity unit are combined by using classical click chemistry to simply and efficiently synthesize the 2,4,6-trisubstituted pyrimidine compounds containing 1,2,3-triazole in an environment-friendly manner. The 2,4,6-trisubstituted pyrimidine compounds containing 1,2,3-triazole have a structure general formula as shown in the specification. In vitro anticancer activity tests show that the compounds have a certain inhibition effect on many tumor cells including EC-109, MCF-7, MGC-803 and B16 and can be applied to preparation of an antitumor medicine, as a further developed candidate or lead compound.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a class of novel 2,4,6-trisubstituted pyrimidine compounds containing 1,2,3-triazole, their preparation method and their use as a class of new antitumor drugs Application of lead compounds. Background technique [0002] Click chemistry, first proposed by the American chemist Sharpless, who won the Nobel Prize in Chemistry in 2001, currently refers to a class of Cu(I)-catalyzed reactions between azide compounds and alkyne compounds to generate 1,2,3-triazoles Reactions of five-membered ring compounds. Due to its mild reaction conditions, high reaction yield, simple post-treatment of products and many other advantages, it has been widely used in the optimization of drug lead compounds and the construction of compound libraries. 1, 2, 3-triazoles exhibit a variety of biological activities, such as anti-inflammatory, anti-allergic, anti-tuberculosis, antibacterial, anti-HIV activ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/12A61K31/506A61P35/00
CPCC07D403/12
Inventor 刘宏民马立英庞露苹王博张淼户彪郑甲信张恩
Owner ZHENGZHOU UNIV
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