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Pyrazolyl steroid derivatives and preparation method and application thereof

A technology for pyrazolyl steroids and derivatives, which is applied in the field of drug synthesis and can solve problems such as inability to meet the treatment of diseases

Inactive Publication Date: 2015-09-16
PESTICIDE INST XIBEI AGRI & FORESTRY TECHUNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The treatment methods of existing drugs can no longer meet the needs of disease treatment, and there is an urgent need to screen out new anticancer drugs to deal with changing diseases

Method used

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  • Pyrazolyl steroid derivatives and preparation method and application thereof
  • Pyrazolyl steroid derivatives and preparation method and application thereof
  • Pyrazolyl steroid derivatives and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] The preparation of pyrazolyl steroid derivatives of formula (I) by chemical synthesis can be carried out with reference to the following steps.

[0061] (1) Dissolve 6.32g (20mmol) of pregnenolone 1 in a 250mL eggplant-shaped flask with 150mL glacial acetic acid, stir until completely dissolved; then add phenylhydrazine hydrochloride derivatives (22mmol) in batches, stir and sonicate until Dissolve; measure 3.46mL (25mmol) triethylamine, slowly drop it into the reaction system at room temperature, drop it after half an hour, stir at room temperature for 6h until solid precipitates, filter with suction, wash with glacial acetic acid, and dry to obtain the target compound 2.1-2.3 is about 7.8g, the product of this step can be directly used in the next reaction without separation.

[0062] (2) First prepare the visemier reagent: take a well-dried round-bottomed flask, add 20 mL of dried DMF solution, slowly add phosphorus oxychloride solution (4.65 mL, 50 mmol) dropwise un...

Embodiment 2

[0068] The target compound synthesized in Example 1 and the important intermediate are carried out structural identification, and the structure of each compound is passed 1 H-NMR, 13 C-NMR, DEPT135 0 confirm.

[0069] Compound 3.1

[0070] Compound 3.1 is a key intermediate, and its structure was confirmed by single crystal diffraction. The results are as follows.

[0071]

[0072] 1 H-NMR (CDCl 3 ,500MHz): δ(ppm)9.96(s,1H),8.39(s,1H),8.04(s,1H),7.72(d,2H,J=7.5Hz),7.48(t,2H,J=7.5 Hz), 7.34(t, 1H, J=7.5Hz), 5.43-5.42(m, 1H), 4.75(m, 1H), 3.28(t, 1H, J=10.0Hz), 2.60-2.53(m, 1H ),2.38-2.37(m,2H),2.10-2.01(m,2H),1.92-1.79(m,3H),1.68-1.52(m,6H),1.45-1.14(m,5H),1.03(s ,3H), 0.64(s,3H).

[0073] 13 C-NMR (CDCl 3 ,125MHz): δ(ppm)184.90(CH),160.64(CH),155.53(C),139.42(C),139.33(C),130.65(CH),129.59(CH),129.59(CH),127.49( CH), 123.93(C), 122.82(CH), 119.58(CH), 119.58(CH), 73.92(CH), 56.52(CH), 50.14(CH), 48.38(CH), 44.65(C), 38.07( CH 2 ),37.99(CH 2 ),36.95(CH 2 ), 36...

Embodiment 3

[0215] The anti-tumor cell proliferation activity of formula (I) pyrazolyl steroid derivatives, draws by preliminary test, its cancer cell toxicity IC 50 None of the values ​​exceeded 6uM. In this example, several compounds were selected and evaluated for their biological activity.

[0216] The present embodiment adopts RSB method to measure pyrazolyl steroid derivatives of the present invention formula (I) to A549 (human lung adenocarcinoma cell), Hela (cervix cancer cell line), HepG2 (human liver cancer cell) three kinds of tumor cells growth inhibitory activity.

[0217] specific method:

[0218] Accurately weigh 1-3mg of the compound to be tested, use DMSO as solvent, prepare a solution with a concentration of 10mMol / L, and let it stand at room temperature for half an hour until the sample is completely dissolved, then store it for later use.

[0219] Take A549, Hela, and HepG2 cells in the logarithmic growth phase, wash and digest with trypsin to make a cell suspension...

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PUM

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Abstract

The invention discloses pyrazolyl steroid derivatives having a structure shown in the formula (I) in the specification, wherein substituent R1 can be H, nitryl or halogen, substituent R2 can be C1-C6 alkyl, hydroxy-substituted C1-C6 alkyl or monosubstituted or polysubstituted aryl. The synthesis route of the pyrazolyl steroid derivatives takes pregnenolone as a raw material; the method is used for synthesizing the pyrazolyl steroid derivatives for the first time and has the advantages of high yield, easy separation and the like. The pyrazolyl steroid derivatives show inhibitory activity for human lung adenocarcinoma cell, cervical carcinoma cell line and hepatoma carcinoma cell and have a prospect of being developed into anti-cancer drug or medicine compositions.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and specifically relates to various pyrazolyl steroid derivatives, their preferred preparation methods and their application in the preparation of anticancer drugs. Background technique [0002] Steroids are a class of organic compounds that widely exist in organisms and have several physiological functions. Steroids have been developed as drugs very early and more and more. Due to their special structure and activity characteristics, more and more researchers are constantly pursuing the modification of their structure in order to change their activity or new The emergence of beneficial activity. The addition or change of certain functional groups in steroid molecules can greatly improve the efficacy of the compound, reduce the toxic and side effects on the human body, and change the action properties of the compound, making its exclusive action single. [0003] Cancer has always been th...

Claims

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Application Information

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IPC IPC(8): C07J43/00A61K31/58A61P35/00
CPCC07J43/003
Inventor 师宝君李健张继文赵西梅吴文君
Owner PESTICIDE INST XIBEI AGRI & FORESTRY TECHUNIV
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