Unlock instant, AI-driven research and patent intelligence for your innovation.

Diarylpyrazole compound and its preparation method and application

A technology of diarylpyrazoles and compounds, applied in the field of diarylpyrazoles and their preparation, can solve the problems of prostate cancer no longer effective, solid-state re-emergence, etc.

Active Publication Date: 2017-11-10
SHANDONG UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although androgen deprivation therapy works well for most early-stage prostate cancers, after a period of treatment, most prostate cancers will solidify and become castration-resistant prostate cancer (CRPC). ), at this time androgen receptor antagonists, such as flutamide (Flutamide) and nilutamide (Nilutamide) are no longer effective against prostate cancer, and bicalutamide (Bicalutamide) will become partial agonistic activity, in this In this case, the application of androgen ablation therapy should be stopped or other androgen receptor antagonists should be used, but enzalutamide (Enzalutamide) will develop resistance after a period of application, so a new type of androgen receptor antagonist with novel structure is designed and synthesized agent has become an urgent need

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Diarylpyrazole compound and its preparation method and application
  • Diarylpyrazole compound and its preparation method and application
  • Diarylpyrazole compound and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] The preparation of embodiment 1 intermediate compound 14

[0068] Weighing Weigh 12mmol (1eq) of the intermediate compound 3-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-ethyl carboxylate 5 into a 100mL eggplant-shaped flask, and dissolve it in 30mL of tetrahydrofuran. Weigh 36mmol (1.37g, 3eq) of lithium aluminum hydride, add to the reaction solution in portions under ice bath conditions, react at room temperature for 15 minutes, when no intermediate 4 is detected by TLC, the reaction is complete, and add to the reaction solution under ice bath conditions Add 50mL of ice water dropwise to the solution, evaporate THF under reduced pressure, adjust the pH to 1 with 1mol / L HCl, when the solution is no longer a colloid, extract with ethyl acetate (50mL×3), combine the organic phases, and wash the organic phases with saturated chlorine Wash with sodium chloride, dry, filter, and evaporate the organic solvent under reduced pressure to obtain a white solid.

[0069] The intermedi...

Embodiment 2

[0071] The preparation of embodiment 2 intermediate compound 15

[0072] Weigh 0.8mmol of intermediate compound 14 in a 50mL eggplant-shaped bottle, dissolve it with 10mL of dichloromethane, slowly drop into 1.6mmol of thionyl chloride, and react at room temperature for 1 hour. When no intermediate compound 14 is detected by TLC, the reaction is completed and reduced Dichloromethane and thionyl chloride were evaporated under pressure to obtain a pale yellow solid.

[0073]The intermediate compound 14 used is 3-(4-fluorophenyl)-1-methyl-1H-5-pyrazolyl)methanol, and correspondingly, the obtained intermediate compound is 5-chloromethyl-3-(4- Fluorophenyl)-1-methyl-1H-pyrazole, specifically as follows;

[0074] 5-Chloromethyl-3-(4-fluorophenyl)-1-methyl-1H-pyrazole (15); pale yellow solid, yield: 100%; Mp: 124-126°C; 1 H-NMR (400MHz, DMSO-d 6 )δ (ppm): 7.799 (t, J = 7.2Hz, 2H), 7.227 (t, J = 7.2Hz, 2H), 6.800 (s, 1H), 4.953 (s, 2H), 3.891 (s, 3H) .

Embodiment 3

[0075] The preparation of embodiment 3 target compound 16

[0076] Weigh 0.8mmol (1eq) of substituted aniline in a 50mL eggplant-shaped flask, dissolve it in 12mL of acetone, add 4mmol (553mg, 5eq) of anhydrous potassium carbonate and 0.08mmol (13mg, 0.1eq) of potassium iodide, and dissolve 0.8mmol (179mg, 1eq) ) Intermediate compound 15 was added therein, stirred at room temperature for 8 hours, when the TLC reaction was completed, the reaction was stopped, acetone was evaporated under reduced pressure, the solid was dissolved with 50mL water and 50mL ethyl acetate, the water phase was separated, and the organic phase was saturated with sodium chloride (30mL×1), washed, dried, filtered, the filtrate was taken, the organic solvent in the filtrate was evaporated under reduced pressure, and the obtained solid was separated and purified by silica gel column chromatography to obtain the target compound 16. The elution system is petroleum ether:ethyl acetate=10:1;

[0077] The sub...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a diarylpyrazole compound as well as a preparation method and application of the diarylpyrazole compound. The structure is shown as a general formula (I) shown as the accompanying drawing, wherein R1 is hydrogen, halogen or methyl; R2 is hydrogen, cyanogroup, trifluoromethyl or halogen; R3 is hydrogen, halogen or nitrile groups; X shown as the formula is carbamoyl, thioureido, methylamino or aminomethyl. The diarylpyrazole compound, particularly 11aM01, 11aM02, 11M04, 13aM01, 16aM01, 16aM02, 16aM10, 16aM11, 16aM12 and 16aM15 have higher cell growth inhibition activity on prostate cancer cells LNCaP and PC-3, 11aM03, 12aM01, 12aM02, 16aM05, 16aM06, 16aM07, 16aM08, 16aM13 and 16aM16 have higher selectivity on prostate cancer cells LNCaP, and all compounds can be used for preparing antineoplastic medicine.

Description

technical field [0001] The invention relates to the fields of organic compound synthesis and medical application, in particular to diarylpyrazole compounds and their preparation methods and applications. Background technique [0002] Prostate cancer (PCa) is one of the most common tumors in men and the fourth most common tumor in the world. In the United States alone, 200,000 people are diagnosed with prostate cancer every year. One in five males over the age of ten will be diagnosed with this life-threatening condition. [0003] The main method for the treatment of metastatic prostate cancer is androgen deprivation therapy (androgen deprivation therapy, ADT, also known as castration therapy), including the inhibition of androgen biosynthesis and the application of androgen receptor antagonists, thereby blocking the interaction between androgen and receptors binding to block the transcription and translation of downstream genes. Although androgen deprivation therapy works ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D231/40C07D231/38C07D231/12A61P35/00
CPCC07D231/12C07D231/38C07D231/40
Inventor 赵桂森郭广柱刘建珍王冠杰张道广陆锦杰
Owner SHANDONG UNIV