Polar amino acid-modified indole ethanol derivative and its synthesis, activity and application

A technology of indole and ethoxyacetyl, which is applied in the field of biomedicine and can solve problems such as toxic and side effects

Inactive Publication Date: 2018-12-25
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

That is to say, this type of bis-indole alcohol benzyl amino acid faces a greater risk of toxic and side effects
The second point of dissatisfaction is that the minimum effective dose for them to play the triple role of anti-tumor, anti-tumor metastasis and anti-inflammation is 0.2μmol / kg, which is too high

Method used

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  • Polar amino acid-modified indole ethanol derivative and its synthesis, activity and application
  • Polar amino acid-modified indole ethanol derivative and its synthesis, activity and application
  • Polar amino acid-modified indole ethanol derivative and its synthesis, activity and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Example 1 Preparation of 1-ethoxycarbonylmethyl-3-ethoxycarbonylmethoxyethyl-indole (1)

[0016] Slowly add 2.98g (4mmol, 60%) NaH to a solution of 5.00g (31mmol) indole alcohol and 50mL anhydrous tetrahydrofuran (THF) at room temperature, and slowly add 17.22mL (5mmol) ethyl bromoacetate after stirring for 30 minutes , heated at 80°C for 48 hours. TLC (petroleum ether / ethyl acetate, 3 / 1) showed the reaction was complete. Heating was stopped and the reaction mixture was cooled to room temperature. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3 / 1) to obtain 1.54 g (15%) of the title compound as a yellow syrup. ESI-MS(m / e):334[M+H] + .

Embodiment 2

[0017] Embodiment 2 prepares 1-carboxymethyl-3-carboxymethoxy ethyl indole (2)

[0018] 1.31 g (3.9 mmol) of 1-ethoxycarbonylmethyl-3-ethoxycarbonylmethoxyethyl-indole (1) was dissolved in 10 mL of methanol under ice cooling. A 2N NaOH aqueous solution was added dropwise to the obtained solution to adjust the pH of the solution to 12. After stirring for 5 hours, TLC (petroleum ether / ethyl acetate, 3 / 1) showed that the reaction was complete. The reaction mixture was saturated with KHSO 4 The pH of the aqueous solution was adjusted to 7, concentrated under reduced pressure, the residue was extracted 3 times with 15 mL ethyl acetate, and the aqueous layer was washed with saturated KHSO 4 The aqueous solution was adjusted to pH 4 and extracted 3 times with 15 mL of ethyl acetate. The separated aqueous layer continued to be saturated with KHSO 4 Adjust the pH to 2 with aqueous solution, extract 3 times with 15 mL ethyl acetate and combine the separated ethyl acetate layers, wash...

Embodiment 3

[0019] Example 3 Preparation of 1-(acetyl-Ser-OBzl)-3-(ethoxyacetyl-Ser-OBzl) indole (3a)

[0020] A solution of 0.55 g (2.0 mmol) of 1-carboxymethyl-3-carboxymethoxyethyl-indole (2), 0.54 g (4.0 mmol) of N-hydroxybenzotriazole and 10 mL of anhydrous THF was stirred After 30 minutes, reaction solution A was obtained. 0.82 g (4.0 mmol) of dicyclohexylcarbodiimide was dissolved in 5 mL of anhydrous THF to obtain a reaction solution B. Under ice-cooling, the reaction solution B was slowly added dropwise to the reaction solution A, and stirred for 30 minutes. Then add a solution of 1.85g (8.0mmol) HCl·Ser-OBzl and 15mL anhydrous THF to it. The reaction mixture was adjusted to pH 9 with N-methylmorpholine and stirred at room temperature for 10 hours. TLC (CH 2 Cl 2 / CH 3 OH, 30 / 1, plus 3 drops of acetic acid) showed completion of the reaction. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was dissolved in 30 mL of et...

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Abstract

The invention discloses 1-(acetyl-AA-OBzl)-3-(ethoxyacetyl-AA-OBzl)indole shown as a formula below, which is shown in the description, (wherein, AA is L-Ser residue, L-Thr residue, L-Gln residue, L-Asn residue and L-Cys(Bzl) residue), and also discloses their preparation method, antitumor activity, anti-tumor-metastasis activity, and anti-inflammatory activity. Therefore, the invention discloses their application in the preparation of antitumor drugs, anti-tumor-metastasis drugs and anti-inflammatory drugs.

Description

technical field [0001] The present invention relates to 1-(acetyl-AA-OBzl)-3-(ethoxyacetyl-AA-OBzl)indole, to their preparation method, to their antitumor activity, to their antitumor metastasis activity, and Involving their anti-inflammatory activity, so the present invention relates to their application in the preparation of anti-tumor drugs, anti-tumor metastasis drugs and anti-inflammatory drugs. The invention belongs to the field of biomedicine. Background technique [0002] Malignant tumors seriously threaten human health. Lung cancer is one of the most aggressive human cancers. For patients with advanced lung cancer, usually 10%-15% of them can only survive for 5 years. This difficult situation has not improved significantly over the past 30 years. In many clinical cases, lung cancer has metastasized to surrounding tissues before being diagnosed. Tumor metastasis, especially tumor lung metastasis is the greatest risk of death in cancer patients. So far, there is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/12A61K31/404A61P35/00A61P29/00
CPCC07D209/12
Inventor 赵明彭师奇王玉记吴建辉甘太平吴晨
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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