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Preparation method and application of one group of pyrazolyl steroid derivative with antitumor activity

A technology of pyrazolyl steroids and anticancer activity, which is applied in the direction of organic active ingredients, medical preparations containing active ingredients, steroids, etc., and can solve problems such as unsatisfactory treatment of diseases

Inactive Publication Date: 2017-06-20
NORTHWEST A & F UNIV
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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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  • Preparation method and application of one group of pyrazolyl steroid derivative with antitumor activity
  • Preparation method and application of one group of pyrazolyl steroid derivative with antitumor activity
  • Preparation method and application of one group of pyrazolyl steroid derivative with antitumor activity

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Preparation of Pyrazolyl Steroid Derivatives of Formula (I) by Chemical Synthesis

[0026] (1) Dissolve 6.32g (20mmol) of pregnenolone in a 250mL eggplant-shaped flask with 150mL of glacial acetic acid, stir until it is completely dissolved, then add phenylhydrazine (22mmol) in batches, stir and ultrasonically until dissolved, and measure 3.46mL (25mmol) triethylamine was slowly dripped into the reaction system at normal temperature, and the dripping was completed after half an hour, and stirred at normal temperature for 6h until solids were precipitated, filtered by suction, washed with glacial acetic acid, and dried to obtain about 7.8g of target compounds 2 and 8, This product was directly used in the next reaction without isolation.

[0027] (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 under stirring, and drop the solution after ...

Embodiment 2

[0032] Compound structure identification, the structures of the three compounds synthesized by 1 H-NMR, 13 Confirmed by C-NMR and high resolution mass spectrometry (HRMS).

[0033] 1 H-NMR, 13 C-NMR and HRMS data are as follows:

[0034] 17β-(1-phenyl-4-((methylamino)methyl)-3-pyrazolyl)androst-3β-ol(5a)

[0035] 5a, white solid, Yield: 88%, mp 204-206℃; 1 H-NMR (CDCl 3 &CD 3 OD, 500MHz): δ(ppm) 8.09(s, 1H), 7.67(d, 2H, J=8.5Hz), 7.43(t, 2H, J=7.0Hz), 7.26(t, 1H, J=7.5Hz ), 3.90-3.80(m, 2H), 3.58-3.53(m, 1H), 2.74(t, 1H, J=9.5Hz), 2.53(s, 3H, CH 3), 2.47-2.40(m, 1H), 2.01-1.93(m, 1H), 1.78-1.70(m, 4H), 1.56-1.54(m, 3H), 1.40-1.10(m, 12H), 1.00-0.93 (m, 2H), 0.81 (s, 3H, CH 3 ), 0.73-0.67 (m, 1H), 0.64 (s, 3H, CH 3 ); 13 C-NMR (CDCl 3 &CD 3 OD, 125MHz): δ(ppm) 152.48, 140.02, 129.29, 129.29, 127.45, 126.18, 118.91, 118.91, 115.61, 70.81, 56.33, 54.53, 48.39, 44.91, 44.79, 44.33, 39.56, 37 , 33.17, 32.07, 31.04, 28.65, 26.66, 24.43, 21.07 (CH 3 ), 13.33 (CH 3 ),...

Embodiment 3

[0055] Anti-tumor cell proliferation activity of pyrazolyl steroid derivatives of formula (I) of the present invention

[0056] Adopt RSB method to measure the pyrazolyl steroid derivative of formula (I) of the present invention to four kinds of cells of A549 (human lung adenocarcinoma cell), Hela (cervix cancer cell line), MCF7 (human liver cancer cell line), 293T cell line growth inhibitory activity.

[0057] Specific method: Accurately weigh 1-3mg of the compound to be tested, use DMSO as solvent, prepare a solution with a concentration of 10mMol / L, let it stand at room temperature for half an hour until the sample is completely dissolved, and store it for later use. Take A549, Hela, 293T, MCF7 cells in the logarithmic growth phase, wash and digest with trypsin to make a cell suspension, count the cells and dilute to an appropriate concentration, and add the cell suspension evenly to a 96-well plate, each well 100ul, three replicates were set for each group, and negative c...

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Abstract

The invention discloses a preparation method and application of one group of pyrazolyl steroid derivative with antitumor activity, which belong to the technical field of medicine synthesis. The preparation method comprises the steps of generating phenylhydrazones 2 and 8 under the catalysis of isopregnenolone 1,5,16-diene progesterone and phenylhydrazine acetic acid; then carrying out ring closing reaction under the catalysis of phosphorus oxychloride to obtain compounds 3 and 9 with pyrazolyl heterocycle; then hydrolyzing to obtain compounds 4 and 10 without formyl groups; carrying out reduction with sodium borohydride to obtain 6; carrying out amination reduction reaction on the intermediate products 4 and 10 and amine under the catalysis of sodium triacetoxy borohydride to obtain 5a-e and 11a-e. The preparation method provided by the invention has the advantages of novel route, high yield and easiness for separation, and the route is an optimal route for preparing the compound.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and relates to a preparation method and application of a group of pyrazolyl steroid derivatives with anticancer activity. Background technique [0002] Cancer has always been the greatest threat to human health. Although the current prevention and treatment methods have been developed, the number of patients dying of cancer is still increasing every year. 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 variable diseases. Based on the advantages of low toxicity of steroid drugs, high utilization rate, and resistance to drug resistance, more and more steroid drugs have been developed. Contents of the invention [0003] The object of the present invention is to provide a group of preparation methods and applications of pyrazolyl steroid derivatives with anticancer activity...

Claims

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Application Information

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IPC IPC(8): C07J43/00A61K31/58A61P35/00
CPCC07J43/003
Inventor 师宝君李健张继文吴文君
Owner NORTHWEST A & F UNIV
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