A kind of substituted phenyl indoline carbazole derivative and its preparation method and application

A technology of substituted phenylindolecarbazole and phenylindolecarbazole, which is applied in the field of substituted phenylindolecarbazole derivatives and their preparation, can solve the problem of insensitivity to chemotherapeutic drugs and resistance to It can reduce the level of ROS, induce apoptosis and autophagy, and achieve the effect of simple synthesis method.

Inactive Publication Date: 2018-02-27
FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Although the level and curative effect of leukemia chemotherapy have been continuously improved, the insensitivity to chemotherapy drugs and the effect of relapsed refractory leukemia after remission are still unsatisfactory (currently etoposide (VP-16) podophyllin derivatives are the most effective treatment for refractory leukemia It is an important therapeutic drug, but there are adverse reactions such as bone marrow suppression, gastrointestinal reactions, skin reactions, and neurotoxicity), and the common problems are large toxic and side effects, drug resistance, and unsatisfactory curative effects, etc.

Method used

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  • A kind of substituted phenyl indoline carbazole derivative and its preparation method and application
  • A kind of substituted phenyl indoline carbazole derivative and its preparation method and application
  • A kind of substituted phenyl indoline carbazole derivative and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Embodiment 1: Preparation of indoline carbazole phenol (Ar is p-hydroxyphenyl, numbering is ZW2-1)

[0042] Add 492 mg (2 mmol) of bis-indolylmethane and 146 mg (1.2 mmol) of p-hydroxybenzaldehyde into a 50 mL round bottom flask, add 30 mL of absolute ethanol and stir to dissolve. Add 0.2 mL of concentrated sulfuric acid dropwise under ice-cooling, and stir thoroughly for 5 minutes. After reacting at room temperature for 24 hours, it was detected by TLC that the starting point of bisindolylmethane disappeared, the reaction was stopped, and the reaction solution was concentrated to dryness under reduced pressure. The residue was dissolved in 30mL ethyl acetate, transferred to a 100mL separatory funnel, washed successively with saturated aqueous sodium bicarbonate (10mL×3) and saturated aqueous sodium chloride (10mL×3), and the ethyl acetate layer was washed with anhydrous Dry over sodium sulfate for 2 hours, filter, and concentrate the filtrate to dryness under reduced ...

Embodiment 2

[0044] Embodiment 2: Preparation of indoline carbazole phenol (Ar is 3-carboxy-4-hydroxyl phenyl, numbering is ZW2-2)

[0045] Add 492mg (2mmol) of bisindolylmethane and 218mg (1.2mmol) of syringaldehyde into a 50mL round bottom flask, add 30mL of absolute ethanol and stir to dissolve. Add 0.2 mL of concentrated sulfuric acid dropwise under ice-cooling, and stir thoroughly for 5 minutes. After reacting at room temperature for 24 hours, it was detected by TLC that the starting point of bisindolylmethane disappeared, the reaction was stopped, and the reaction solution was concentrated to dryness under reduced pressure. The residue was dissolved in 30mL ethyl acetate, transferred to a 100mL separatory funnel, washed successively with saturated aqueous sodium bicarbonate (10mL×3) and saturated aqueous sodium chloride (10mL×3), and the ethyl acetate layer was washed with anhydrous Dry over sodium sulfate for 2 hours, filter, and concentrate the filtrate to dryness under reduced pr...

Embodiment 3

[0047] Example 3: Preparation of indoline carbazole phenol (Ar is 3,5-dimethoxy-4-hydroxyphenyl, numbered ZW2-3)

[0048] Add 492mg (2mmol) of bisindolylmethane and 180mg (1.1mmol) of salicylaldehyde into a 50mL round bottom flask, add 30mL of absolute ethanol and stir to dissolve. Add 0.2 mL of concentrated sulfuric acid dropwise under ice-cooling, and stir thoroughly for 5 minutes. After reacting at room temperature for 24 hours, it was detected by TLC that the starting point of bisindolylmethane disappeared, the reaction was stopped, and the reaction solution was concentrated to dryness under reduced pressure. The residue was dissolved in 30mL ethyl acetate, transferred to a 100mL separatory funnel, washed successively with saturated aqueous sodium bicarbonate (10mL×3) and saturated aqueous sodium chloride (10mL×3), and the ethyl acetate layer was washed with anhydrous Dry over sodium sulfate for 2 hours, filter, and concentrate the filtrate to dryness under reduced pressu...

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Abstract

The invention discloses a substituted phenyl indoline carbazole derivative and a preparation method and application thereof. Please see the structural formula in formula I, wherein Ar adopts hydroxyphenyl or 3-carboxyl-4-hydroxyphenyl or 3,5-dimethoxy-4-hydroxyphenyl. The substituted phenyl indoline carbazole derivative can obviously lower the ROS level in a leukemia cell and can serve as a candidate compound of an antineoplastic drug and / or an anti-leukemia chemotherapeutic agent and / or a leukemia differentiation inducer.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a substituted phenylindolecarbazole derivative and a preparation method and application thereof. Background technique [0002] According to the statistics of the World Health Organization in 2002, there are about 300,000 new cases of leukemia every year in the world, and the death toll is about 220,000, ranking ninth among fatal malignant tumors. Leukemia is one of the top ten high-incidence malignant tumors in my country, accounting for the sixth place in the incidence of tumors. The incidence of leukemia in my country is about 3 / 100,000-4 / 100,000 population. With the continuous development of leukemia treatment, autologous bone marrow transplantation, allogeneic bone marrow transplantation, stem cell transplantation and gene therapy have made great progress, but all these treatments require effective chemotherapy as the basis. [0003] There are more than 30 chemotherapy dru...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04A61K31/403A61P35/02
CPCC07D487/04
Inventor 章金刚王文敬吕茂民赵雄
Owner FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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