Ursolic acid pyrimidine amide derivative as well as preparation method and application thereof

A technology of ursolic acid pyrimidine amide and fruit acid pyrimidine amide, which is applied in the field of ursolic acid pyrimidine amide derivatives and its preparation, can solve problems such as threats to human health and difficulties in cancer treatment, and achieve novel structural effects

Active Publication Date: 2021-06-22
NANJING FORESTRY UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Because many reasons may induce the occurrence of cancer, and the treatment

Method used

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  • Ursolic acid pyrimidine amide derivative as well as preparation method and application thereof
  • Ursolic acid pyrimidine amide derivative as well as preparation method and application thereof
  • Ursolic acid pyrimidine amide derivative as well as preparation method and application thereof

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preparation example Construction

[0031] The preparation method of I-a to I-p of pyrimidine amide derivatives of ursolic acid comprises the steps:

[0032] (1) ursolic acid obtains 3-oxidized ursolic acid through Jones reagent oxidation reaction, and structural formula is as shown in formula II:

[0033]

[0034] (2) Benzaldehyde of different substituents carries out ClaisenSchmidt condensation reaction with 3-oxidized ursolic acid under the effect of KOH / Ethanol to obtain corresponding benzylidene ursolic acids containing different substituents, and the structural formula is as shown in formula III:

[0035]

[0036] (3) The benzylidene ursolic acid III of different substituents obtains the amide compound of the corresponding benzylidene ursolic acid under the effect of DCC / HOBt, and the structural formula is as shown in formula IV:

[0037]

[0038] (4) Benzylidene ursolic acid amide compounds with different substituents react with guanidine hydrochloride under potassium tert-butoxide alkaline condi...

Embodiment 1

[0040]The synthesis of ursolic acid pyrimidine amide (I-a) comprises the following steps:

[0041] (1) Add 4.6mmol of ursolic acid and 250mL of acetone to a 500mL round bottom flask, stir to dissolve, stir in ice water for 15min, slowly add 1.87mL of Jones reagent dropwise and rise to room temperature, stir for 5h, then add 90mL of iso Propanol stirring reaction 30min, after the reaction finishes, filter and precipitate and collect the filtrate, the light yellow-green viscous solid obtained by concentrating the filtrate under reduced pressure obtains the white needle-shaped crystals obtained by methanol recrystallization, and makes 3-oxidized ursolic acid (II) ( 1.2g, 65.6%);

[0042] (2) Take by weighing 1.1 equivalents (relative to 3-oxidized ursolic acid) of benzaldehyde in a round bottom flask, add 20mL of absolute ethanol as a solvent, and take by weighing 0.5g of catalyst potassium hydroxide, and prepare a mass fraction of 2.5 % potassium hydroxide ethanolic solution, a...

Embodiment 2

[0047] Synthesis of Pyrimidinamide Ursolic Acid (I-b)

[0048] Using 4-fluorobenzaldehyde and 3-dimethylamino-1-propylamine as raw materials, prepare the benzylidene ursolic acid amide compound IV-b by the above method, and dissolve 0.001mol of compound IV-b in 10mL of tert-butyl Alcohol, slowly dissolve 0.005mol potassium tert-butoxide and 0.004mol guanidine hydrochloride in the reaction solution in turn, slowly rise to 85°C and stir and reflux for 24 hours. After the reaction is completed, extract the organic phase 3 times with ethyl acetate, wash 3 times with water, Wash once with saturated sodium bicarbonate solution and concentrated brine, remove water with anhydrous sodium sulfate, concentrate under reduced pressure to remove organic solvent to obtain a white solid, separate and purify it with an alumina column, and use dichloromethane / methanol as the gradient elution solvent (200:1-100:1), the product components were combined, concentrated under reduced pressure, and th...

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Abstract

The invention discloses an ursolic acid pyrimidine amide derivative as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis and medicinal chemistry. The structural formula of the ursolic acid pyrimidine amide derivative is as shown in formula I. The preparation of the ursolic acid pyrimidine amide derivative comprises the following steps: oxidizing C-3 hydroxyl on an ursolic acid A ring into carbonyl, reacting with benzaldehyde with different substituent groups to obtain a benzylidene ursolic acid derivative, and reacting with different amines under the action of DCC/HOBt to generate an amide group, and reacting the ursolic acid amide derivative with guanidine hydrochloride in an alkaline environment to obtain the finished compound. The compound has a remarkable inhibition effect on human lung cancer cells A549, human breast cancer cells MCF-7, human cervical cancer cells HeLa and human hepatoma cell lines Hep G2, shows low toxicity on human normal hepatic epithelial cells Ges-1, and has the potential of developing and preparing antitumor drugs.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis and medicinal chemistry, and in particular relates to ursolic acid pyrimidine amide derivatives and their preparation methods and applications. Background technique [0002] There are two types of tumors: malignant and benign. Malignant tumors refer to a common disease in which cells have lost self-control and threaten personal life, which is the so-called cancer. Because many reasons may induce cancer, and the treatment of cancer is very difficult, it has brought a huge threat to human health. Conquering cancer has become a arduous and meaningful task that medical and chemical workers must face. In the process of clinical treatment of tumors, comprehensive treatment methods are mainly adopted. Chemotherapy is a means to block cell growth, inhibit or directly kill cancer cells. Chemical drugs are used to suppress cancer cells and treat various tumors. Disease is a fast and efficient me...

Claims

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Application Information

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IPC IPC(8): C07J71/00A61P35/00
CPCA61P35/00C07J71/0047
Inventor 谷文王文燕李阿良刘青松孙月王石发
Owner NANJING FORESTRY UNIV
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