Indole or azaindole derivatives as well as preparation method and application thereof

A technology of indoles and derivatives, applied in the field of medicine, can solve the problems of weak pharmacodynamic activity, high nephrotoxicity, large dose and the like

Active Publication Date: 2018-05-04
CHINA RESOURCES SAIKE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] Lesinurad has problems such as weak drug activity and large dose, which brings about high

Method used

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  • Indole or azaindole derivatives as well as preparation method and application thereof
  • Indole or azaindole derivatives as well as preparation method and application thereof
  • Indole or azaindole derivatives as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 12

[0200] Example 1 2-[[1-(4-cyanonaphthalen-1-yl)-1H-indol-3-yl]mercapto]acetic acid (I1)

[0201]

[0202] Step 1: 2-[(1H-Indol-3-yl)mercapto]acetic acid

[0203] Indole (2.9g) was dissolved in methanol (30mL), thiourea (12g) was added, a mixed aqueous solution (50mL) of iodine (6.4g) and potassium iodide (4.2g) was added dropwise at room temperature, and the reaction was stirred at room temperature, TLC Monitor the completion of the reaction. Add NaOH solution (2M, 125mL), and stir at 100oC for 10min. Add methyl bromoacetate (4.9g), and stir the reaction at room temperature for 2h. After the TLC reaction was complete. Extract with ethyl acetate (300mL) and water (100mL), wash the ethyl acetate phase with saturated brine (100mL*4), dry the organic phase over anhydrous sodium sulfate, filter, concentrate under reduced pressure, and purify by column chromatography (eluent , dichloromethane:methanol=10:1, v:v), 800 mg of pure product was obtained, and the yield was 15.6%. ...

Embodiment 2

[0207] Example 2 Sodium 2-[[1-(4-cyanonaphthalen-1-yl)-1H-indol-3-yl]mercapto]acetate (I2)

[0208] Dissolve 2-[[1-(4-cyanonaphthalen-1-yl)-1H-indol-3-yl]mercapto]acetic acid (100mg, 0.279mmol) in 5mL methanol, add sodium hydroxide solution (1M , 0.279mL), stirred at room temperature for 10 minutes, concentrated to dryness under reduced pressure to obtain 106 mg of white solid, yield 100%, LC-MS: m / z 359.1 [M+H] + .

Embodiment 32

[0209] Example 3 2-[[1-(4-cyanonaphthalen-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]mercapto]acetic acid (I3)

[0210] Using 7-azaindole as raw material instead of indole, the synthesis method is the same as the preparation method of the compound described in Example 1, LC-MS: m / z 360.1 [M+H] + .

[0211] 1 H NMR (400MHz, DMSO-d 6 ): δ=12.70(s,1H),8.54(d,J=6,4Hz,1H),8.51(t,J=7.6Hz,1H),8.36(d,J=8.4Hz,1H),8.12( s,1H),7.98(d,J=7.6Hz,1H),7.81(d,J=8.0Hz,1H),7.72(t,J=8.0Hz,1H),7.50(t,J=8.0Hz, 1H), 7.45(d, J=6.4Hz, 1H), 7.32(d, J=7.6Hz, 1H), 3.79(s, 2H).

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Abstract

The invention belongs to the field of medicine. In particular, the invention relates to a preparation method of a series of indole or azaindole derivatives and medicinal salt thereof, a medicinal composition containing the derivatives, and application of the derivatives and the medicinal composition to preparation of anti-gout medicines and treatment on related diseases. The structural formula ofthe compound is shown in the description.

Description

technical field [0001] The present invention belongs to the field of medicine, in particular, the present invention relates to a series of indole or azaindole derivatives and preparation methods of pharmaceutically acceptable salts thereof, pharmaceutical compositions containing said derivatives, and said derivatives Uses of medicines and pharmaceutical compositions in the preparation of anti-gout drugs and the treatment of related diseases. Background technique [0002] Gout is due to the disorder of purine metabolism in the body and excessive uric acid in the blood, resulting in the precipitation of urate in the joints, kidneys and connective tissues, thereby causing gouty arthritis, gouty nephropathy and stone disease, etc., which are collectively called gout in medicine. The disease is characterized by birefringent sodium urate monohydrate crystals found in joint fluid and tophi. Its clinical features are: hyperuricemia and urate crystals, characteristic acute arthritis...

Claims

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Application Information

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IPC IPC(8): C07D209/30C07D471/04A61K31/404A61K31/437A61P19/06A61P19/02A61P13/04A61P13/12
CPCC07D209/30C07D471/04
Inventor 杨琰王奇昌扈占坤秦至臻卞德乾刘海云
Owner CHINA RESOURCES SAIKE PHARMA
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