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5-Hydroxytryptophan methyl ester derivative with anti-tumor activity and its preparation method and application

A technology for hydroxytryptophan methyl ester and antitumor activity, which is applied in the field of 5-hydroxytryptophan methyl ester derivatives and their preparation, and can solve the problems of unsatisfactory therapeutic effect, enhanced systemic toxic and side effects, and reduced effective drug concentration.

Active Publication Date: 2019-02-22
XINXIANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the main treatment method for malignant tumors is still mainly surgical treatment, supplemented by comprehensive treatment such as chemotherapy, radiotherapy, gene therapy and other biological treatments, but the treatment effect is still not satisfactory. Among them, radiotherapy and chemotherapy are extremely important non-surgical treatments. However, while radiotherapy and chemotherapy kill tumor cells, they also cause serious damage to normal cells in the body.
Due to the lack of targeting of the drug itself, the effective concentration of the drug at the tumor site is reduced, the systemic side effects are enhanced, and there are treatment problems such as low cure rate, multidrug resistance, and large toxic and side effects.

Method used

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  • 5-Hydroxytryptophan methyl ester derivative with anti-tumor activity and its preparation method and application

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Effect test

Embodiment

[0017] Synthesis of 5-hydroxy-N-[[1-(4-tert-butylbenzyl)-1H-1,2,3-triazol-4-yl]carbonyl]-D-tryptophan methyl ester :

[0018]

[0019] a: NaN 3 , DMF, rt, 12h; b: CuSO 4 , Sodium ascobate, THF-H 2 O(1:1), rt, 5h; c: LiOH, THF-MeOH-H 2 O(4:2:1), rt, over night; d: SOCl 2 , MeOH, reflux, 5h; e: EDC·HCl, HOBt, DMF, triethylamine, rt, over night.

[0020] The specific steps of the synthesis process are:

[0021] 1) Synthesis of 5-hydroxytryptophan methyl ester

[0022] Add 44.00 g (0.2 mol) of 5-hydroxytryptophan and 350 mL of methanol into a 500 mL three-necked flask, cool down to -5°C, and slowly add 17.4 mL (0.24 mol) of thionyl chloride dropwise at low temperature. After the dropwise addition, the temperature was raised to 35° C. to react overnight. TLC detects that the raw material disappears and stops the reaction. Methanol was distilled off under reduced pressure, and after cooling, 300 mL of ethyl acetate was added to stir, filtered with suction, and dried to o...

experiment example 1

[0032] The purpose of this test example is to study the in vitro anti-tumor cell proliferation activity of the compound of the present invention

[0033] Human esophageal squamous cell carcinoma cells (TE-1), human gastric carcinoma cells (MGC803), and human colon carcinoma cells (HCT116) in the logarithmic growth phase were divided into 6×10 3 Each well was inoculated into a 96-well plate, and after 24 hours of culture, the medium was replaced with 5-hydroxy-N-[[1-(4-tert-butylbenzyl)-1H-1,2,3-triazol Azol-4-yl]carbonyl]-D-tryptophan methyl ester medium, 9 concentrations for each sample, respectively 128, 64, 32, 16, 8, 4, 2, 1, 0.5 μg / mL, A blank control group was set up, and culture continued for 72 hours. After the culture is over, add 20 μL of MTT to each well, discard the medium after four hours, add 150 mL of DMSO to each well, measure the OD value with a microplate reader at a wavelength of 490 nm after shaking evenly, and calculate the IC of the compound using SPSS s...

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Abstract

The invention discloses a 5-hydroxytryptophan methyl ester derivative with anti-tumor activity and its preparation method and application, specifically 5-hydroxy-N-[[1-(4-tert-butylbenzyl) ‑1H‑1,2,3‑triazole‑4‑yl]carbonyl]‑D‑tryptophan methyl ester, its structural formula is:. The invention also discloses the preparation method of the 5-hydroxytryptophan methyl ester derivative with antitumor activity and its application in the preparation of antitumor drugs. The compound synthesized by the invention has good anti-tumor cell proliferation activity in vitro, and is significantly inhibited on the growth of TE-1, MGC803 and HCT116 cells, and can be further developed as an anti-tumor drug or a lead compound.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a 5-hydroxytryptophan methyl ester derivative with antitumor activity and a preparation method and application thereof. Background technique [0002] Malignant tumor is an important disease that endangers human health, and its mortality rate is the second largest disease after cardiovascular and cerebrovascular diseases. At present, the main treatment method for malignant tumors is still mainly surgical treatment, supplemented by comprehensive treatment such as chemotherapy, radiotherapy, gene therapy and other biological treatments, but the treatment effect is still not satisfactory. Among them, radiotherapy and chemotherapy are extremely important non-surgical treatments. However, while radiotherapy and chemotherapy kill tumor cells, they also cause serious damage to normal cells in the body. Due to the lack of targeting of the drug itself, the effectiv...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D403/12A61P35/00A61P35/02
CPCC07D403/12
Inventor 赵杰刘兆敏马矜烁吴娇
Owner XINXIANG MEDICAL UNIV