Fujisu and its preparation method and application

A post-reaction technology of phexidine, applied in the field of medicine, can solve problems such as poor prognosis of surgery and unsatisfactory results of cholangiocarcinoma

Active Publication Date: 2020-05-29
SHANDONG NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the principle of treatment for cholangiocarcinoma is still based on the comprehensive treatment plan of surgical resection, but less than 1 / 3 of the patients can be surgically resected at the time of diagnosis, and the prognosis of surgery is poor. The effect of combined chemotherapy on locally advanced or metastatic unresectable cholangiocarcinoma Not ideal, urgent need to develop new therapeutic drugs
These compounds are mainly alkaloid derivatives, and have not achieved ideal effects in anti-pancreatic cancer and anti-cholangiocarcinoma

Method used

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  • Fujisu and its preparation method and application
  • Fujisu and its preparation method and application
  • Fujisu and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Weigh 18.30g of fangchinoline base and 0.72g of sodium hydride, dissolve it in 200mL of methanol and put it in a 500mL three-neck flask, then add 4.50g of o-fluorobenzyl chloride, stir and heat at 65°C, and keep stirring for 72h. TLC detects fangchinoline base For the whole reaction, distill methanol off, cool down to room temperature, add 80 mL of water, extract 3 times with dichloromethane (300 mL×3), trace the separation and purification process of the reaction and product by TLC, recover dichloromethane from the extract, and store the solid at 60°C After drying for 4 hours, 17.21 g of a light yellow powder was obtained. The melting point of the target product: 152.2-153.9°C, 13 C NMR (CDCl 3 ,100MHz)δ160.31,157.86,152.79,150.36,148.34,147.81,147.38,146.09,142.95,135.61,133.89,133.77,131.60,129.39,127.96,127.46,126.94,126.50,123.74,122.76,122.12,121.79,120.81,119.34 . TOF-HRMS: M / e (716.8477), molecular formula: C 44 h 45 o 6 N 2 F, namely compound 1 in Table ...

Embodiment 2

[0070] Weigh 18.30g of fangchinoline base, 2.10g of sodium ethoxide and dissolve it in 200mL of absolute ethanol in a 500mL three-neck flask, then add 5.80g of p-fluorobenzyl bromide, stir and heat at 78.5°C, keep stirring for 36h, and detect fangchinoline by TLC Lin alkali reacted completely, distilled out absolute ethanol, cooled to room temperature, added 80mL of water, extracted 3 times with chloroform (300mL×3), followed the separation and purification process of reaction and product by TLC, recovered chloroform from the extract, solid Dry at 60°C for 4 hours to obtain 17.85 g of a light yellow powder. The melting point of the target product: 153.1-154.7°C, 13 C NMR (CDCl 3 ,100MHz)δ163.55,161.11,153.75,151.39,149.43,148.78,148.52,147.13,143.95,136.68,135.12,134.68,133.31,132.65,130.15,130.09,130.01,128.43,128.26,128.10,123.12,122.82,121.91,120.23 . TOF-HRMS: M / e (716.8474), molecular formula: C 44 h 45 o 6 N 2 F, namely compound 3 in Table 1.

Embodiment 3

[0072] Weigh 6.10g of fangchinoline base and 1.40g of potassium carbonate, dissolve it in 100mL of propanol in a 500mL three-neck flask, then add 2.10g of 2,5-difluorobenzyl bromide, heat and stir at 98°C, and keep stirring for 24h, TLC Detect the entire reaction of fangchinoline base, evaporate the solvent under reduced pressure, cool down to room temperature, add 50 mL of water, extract 3 times with acetone (50 mL×3), trace the separation and purification process of the reaction and the product by TLC, and use anhydrous Na 2 SO 4 After drying for 8 hours, acetone was recovered, and the solid was dried at 60° C. for 4 hours to obtain 5.75 g of a light yellow powder. The melting point of the target product: 151.5-153.2°C, 13 C NMR (101MHz, CDCl 3 )δ153.76,151.22,151.09,149.42,148.73,148.63,148.46,147.08,143.80,136.34,135.32,134.87,134.73–134.56(m),132.65,130.13,128.75,128.60,123.91,123.29,122.80,121.89,120.17, 117.01, 116.83, 116.51, 116.23, 112.97, 111.61, 106.01, 72.85, 6...

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Abstract

The invention provides fujisu as well as a preparation method and application thereof. The fujisu has a structure shown as a formula (I) or a formula (I') shown in the description, wherein R is substituted benzyl or substituted pyridylmethyl; the substituted benzyl is benzyl substituted by one or more substituents selected from halogen, alkyl, alkoxy or halogenated alkyl; the substituted pyridylmethyl is pyridylmethyl substituted by halogen; Y is selected from inorganic acids and organic acids. The compound has the characteristics of the fluoro-substituted benzyl or the fluoro-substituted pyridylmethyl while having a bisbenzylisoquinoline mother core structure; based on 0.2 [mu]g / mL of the fujisu, the inhibition rate on the proliferation of bile duct cancer cells QBC-939 and human pancreatic cancer cells PANC-1 is generally higher than 62 percent; the inhibition rate of most compounds is generally higher than 80 percent, and the activity is much higher than that of clinically-applied fluorouracil.

Description

technical field [0001] The invention relates to the field of medicine, in particular to phexidine and its preparation method and application. Background technique [0002] Pancreatic cancer is a common pancreatic tumor. It is a highly malignant tumor of the digestive tract that is difficult to diagnose and treat. The 5-year survival rate is <1%. Pancreatic cancer is one of the malignant tumors with the worst prognosis due to its low diagnosis rate and high surgical mortality rate. At present, the main therapeutic drugs are fluorouracil, doxorubicin, ifosfamide, semustine, paclitaxel, gemcitabine, cisplatin, etc., but the clinical cure rate is very low. Cancer drugs are very necessary. [0003] Cholangiocarcinoma is a common malignant tumor of the biliary tract (Wang Xiangyu et al. Progress in clinical treatment of hilar cholangiocarcinoma[J], Chinese Electronic Journal of Liver Surgery, 2018, 7(4):253-257), with a high degree of malignancy, The prognosis is extremely p...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D491/18A61P35/00A61K31/4748
Inventor 刘玉法张彦春吕绪涛王继庆王磊王恬慧张一帆井晓琳
Owner SHANDONG NORMAL UNIV
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