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A kind of 3-(indol-5-yl)-indazole derivative and its application

A derivative, indazole technology, applied in the field of 3--indazole derivatives and its application, can solve the problems of poor water solubility and low bioavailability

Active Publication Date: 2020-08-25
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these natural products may interact with multiple targets in addition to the MD2-TLR4 pathway, and have defects such as poor water solubility and low bioavailability

Method used

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  • A kind of 3-(indol-5-yl)-indazole derivative and its application
  • A kind of 3-(indol-5-yl)-indazole derivative and its application
  • A kind of 3-(indol-5-yl)-indazole derivative and its application

Examples

Experimental program
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Effect test

Embodiment 13

[0026] The synthesis of embodiment 13-iodo-5-nitro-1H-indazole

[0027] Dissolve 5-nitroindazole (5g, 30.8mmol) in 30mL N, N-dimethylformamide, add iodine (15.66g, 61.6mmol) and potassium hydroxide solid (3.58g, 63.7mmol) in sequence, React at 65°C for 3h. After the reaction, 50 mL of 1M HCl and 80 mL of 10% sodium thiosulfate solution were added, and after stirring for 30 min, ice water was added to the reaction to precipitate a yellow bottom, filtered with suction, and the filter cake was washed with dichloromethane. The filter cake was further recrystallized from ethyl acetate to obtain 7.99 g of the yellow target product, with a yield of 90%.

Embodiment 2

[0028] Example 2 3-iodo-5-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (9a)

[0029] Add sodium hydride (60%; 720mg, 17.99mmol) to 3-iodo-5-nitro-1H-indazole (2g, 6.92mmol) solution in 15mL N,N-dimethylformamide at 0°C, and add after 30min 2-(Trimethylsilyl)ethoxymethyl chloride (1.50mL, 8.30mmol), stirred at room temperature for 3h. After the reaction was completed, it was quenched by adding ice water, extracted by adding ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography to obtain 2.6 g of product with a yield of 90%.

Embodiment 3

[0030] Example 3 Synthesis of 1-benzyl-3-iodo-5-nitro-1H-indazole (9b)

[0031] 3-iodo-5-nitro-1H-indazole (400mg, 1.38mmol) was dissolved in 10mL acetone, potassium carbonate (382mg, 2.76mmol) and benzyl bromide (164μL, 1.38mmol) were added, and the reaction was heated under reflux for 2h. After the reaction was completed, quenched by adding saturated ammonium chloride, the acetone solvent was removed by rotary evaporation, extracted by adding ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed by rotary evaporation, and the crude product was purified by column chromatography to obtain 497.5 mg product, yield 95%.

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PUM

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Abstract

The invention discloses 3-(indol-5-yl)-indazole derivatives. The structure of the 3-(indol-5-yl)-indazole derivatives is shown in formula (I) or (II), in formula (I), R1 is selected from substituted or unsubstituted aryl group or alkyl group; R2 is selected from hydrogen or benzyl group; and R3 is selected from hydrogen or alcoholic group. In formula (II), R1 is selected from nitro group or aminogroup. The research result shows that most of 3-(indol-5-yl)-indazole derivatives have better anti-inflammatory activity and can improve the druggability defect of the lead compound.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to a 3-(indol-5-yl)-indazole derivative and application thereof. Background technique [0002] Inflammation is the body's response to pathogenic factors and their damaging effects. It can usually be divided into two categories according to the course of the disease: acute inflammation and chronic inflammation. A large number of studies have shown that inflammation is closely related to the occurrence and development of various diseases including tumors, coronary heart disease, atherosclerosis and diabetes. Therefore, inflammation has become a hallmark feature of many human diseases. During the development of inflammation, the inflammatory factors closely related to it mainly include tumor necrosis factor-α (Tumor Necrosis Factor-alpha, TNF-α), interleukin-6 (interleukin-6, IL-6) and interleukin-1β, etc. ( interleukin-1β, IL-1β). These inflammatory factors can not only...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D403/04A61K31/416A61P29/00A61P19/02A61P25/00A61P17/06A61P37/02A61P17/00A61P37/00A61P1/16A61P13/00A61P37/08A61P31/04A61P19/06
CPCA61P1/16A61P13/00A61P17/00A61P17/06A61P19/02A61P19/06A61P25/00A61P29/00A61P31/04A61P37/00A61P37/02A61P37/08C07D403/04
Inventor 梁广刘志国王怡蔡跃飘陈凌锋赵云洁
Owner WENZHOU MEDICAL UNIV
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