1-styryl isoquinoline derivative as well as preparation and application thereof

A styryl, methyl isoquinoline technology, applied in the field of medicine, can solve the problems of insignificant early symptoms of gastric cancer, low survival rate of gastric cancer, etc., and achieve inhibition of gastric cancer cell migration and invasion, significant anti-gastric cancer activity, and good anti-gastric cancer. active effect

Pending Publication Date: 2022-04-29
THE FIRST AFFILIATED HOSPITAL HENGYANG MEDICAL SCHOOL UNIV OF SOUTH CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

After endoscopic or surgical treatment of early gastric cancer, the 5-year survival rate can reach more than 90%. However, because the early symptoms of gastric cancer are often not obvious, most patients have already reached the advanced stage when they go to the doctor, so the overall 5-year survival rate of gastric cancer remains low. hovering at a lower level

Method used

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  • 1-styryl isoquinoline derivative as well as preparation and application thereof
  • 1-styryl isoquinoline derivative as well as preparation and application thereof
  • 1-styryl isoquinoline derivative as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] (E)-1-(2-fluorostyryl)isoquinoline (compound 1)

[0035] The structural formula of compound 1 is:

[0036] Put 1-methylisoquinoline (1.0 mol), o-fluorobenzaldehyde (1.1 mol), and p-toluenesulfonamide (1.1 mol) in a 50 mL round-bottomed flask, and replace it with argon, add 10 mL of toluene, and Heat to reflux at 120°C and react for 8 hours. After the completion of the reaction monitored by TLC, the solvent was removed by rotary evaporation, and the compound (E)-1-(2-fluorostyryl)isoquinoline (compound 1) was obtained by column chromatography separation with a yield of 67%. 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.63 (d, J = 8.3Hz, 1H), 8.55 (d, J = 5.5 Hz, 1H), 8.32 (d, J = 15.6 Hz, 1H), 8.21 – 8.11 (m,2H), 7.93 (d, J = 7.8 Hz, 1H), 7.78 – 7.64 (m, 3H), 7.38 (ddd, J = 12.6, 5.7,2.7 Hz, 1H), 7.31 – 7.21 (m, 2H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 160.27 (d, J =248.9 Hz), 153.24, 142.25, 136.22, 130.30 (d, J = 8.5 Hz), 130.09, 128.08 (d, J = 3.0 Hz), 127.49...

Embodiment 2

[0038](E)-1-(2-chlorostyryl)isoquinoline (Compound 2)

[0039] The structural formula of compound 2 is:

[0040] The o-fluorobenzaldehyde in the operating steps of Example 1 was replaced by o-chlorobenzaldehyde, and all the other operating steps were the same as in Example 1, with a yield of 71%. 1 H NMR (400 MHz, Chloroform- d ) δ 8.57 (d, J = 5.6 Hz, 1H), 8.33(d, J = 15.5 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 15.6 Hz, 1H),7.84 – 7.76 (m, 2H), 7.68 – 7.61 (m, 1H), 7.60 – 7.50 (m, 2H), 7.41 (m, 1H),7.28 (td, J = 7.6, 1.4 Hz, 1H), 7.25 – 7.18 (m, 1H). 13 C NMR (101 MHz, DMSO- d 6 ) δ 154.11, 142.50, 136.57, 135.14, 134.28, 131.94, 129.92, 129.79, 129.29, 127.23, 127.19, 127.18, 126.83, 126.68, 120.16.

Embodiment 3

[0042] (E)-1-(2-bromostyryl)isoquinoline (compound 3)

[0043] The structural formula of compound 3 is:

[0044] The o-fluorobenzaldehyde in the operating steps of Example 1 was replaced by o-bromobenzaldehyde, and all the other operating steps were the same as in Example 1, and the productive rate was 83%. 1 H NMR (400 MHz, Chloroform- d ) δ 8.59 (d, J = 5.6 Hz, 1H), 8.37 –8.24 (m, 2H), 7.90 (d, J = 15.5 Hz, 1H), 7.81 (m, J = 7.9, 1.6 Hz, 2H), 7.70– 7.59 (m, 2H), 7.57 (d, J = 5.8 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.17 (m, J = 7.7, 1.6 Hz, 1H). 13 C NMR (101 MHz, Chloroform- d ) δ 154.16, 142.61, 137.03, 136.65, 134.63, 133.24, 129.87, 129.59, 127.55, 127.44, 127.30, 127.26, 126.75, 126.10, 124.808, 2.124

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Abstract

The invention provides a 1-styryl isoquinoline derivative and a preparation method thereof, and the 1-styryl isoquinoline derivative is synthesized by using 1-methylisoquinoline and a benzaldehyde compound as raw materials through an intermolecular nucleophilic addition elimination reaction under the catalysis of p-toluenesulfonamide. The 1-styryl isoquinoline derivative prepared by the invention has good anti-gastric cancer activity, blocks a cell cycle in a G2/M period, and induces cell apoptosis by inhibiting a PI3K/Akt/mTOR pathway. The compound has good cytotoxicity to tumor cells, is simple to synthesize and can be applied to preparation of gastric cancer treatment drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a preparation method of 1-styryl isoquinoline derivatives; the invention also relates to the application of 1-styryl isoquinoline derivatives in the preparation of anti-gastric cancer drugs. Background technique [0002] Gastric cancer is a common malignant tumor in the world, ranking third among the related deaths caused by malignant tumors in the world. More than 70% of the new cases of gastric cancer are in developing countries, and about 50% of the cases are in eastern Asia, mainly concentrated in China. Its death rate ranks second among malignant tumors in China. After endoscopic or surgical treatment of early gastric cancer, the 5-year survival rate can reach more than 90%. However, because the early symptoms of gastric cancer are often not obvious, most patients have already reached the advanced stage when they go to the doctor, so the overall 5-year survival r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/14C07D217/02A61P1/00A61P35/00A61K31/472
CPCC07D217/14C07D217/02A61P1/00A61P35/00
Inventor 王震谢黎明张茜李昭冯益悦卢莹美
Owner THE FIRST AFFILIATED HOSPITAL HENGYANG MEDICAL SCHOOL UNIV OF SOUTH CHINA
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