Sulfonyl fangchinoline compound as well as preparation method and application thereof

A technology of fangchinoline base and compound, which is applied in the field of medicine and can solve the problems of small application range

Active Publication Date: 2021-01-22
SHANDONG NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the common adverse reactions of febuxostat and topinastat mainly include abnormal liver function, headache, diarrhea, vomiting, and joint pain. At the same time, this type of XOD inhibitor is mainly metabolized by the liver, and it is forbidden to use it in patients with hepatic insufficiency. Its use is small

Method used

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  • Sulfonyl fangchinoline compound as well as preparation method and application thereof
  • Sulfonyl fangchinoline compound as well as preparation method and application thereof
  • Sulfonyl fangchinoline compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Dissolve 100.0mg fangchinoline base (about 0.18mmol) in 3mL of dichloromethane, add it into a two-necked flask filled with argon, and place it in a cold well with temperature controlled to 0°C, add the dissolved 2mL under magnetic stirring 66.5 mg (about 0.72 mmol) of triethylamine in dichloromethane was mixed for 1 h, and then 31.0 mg (about 0.27 mmol) of methanesulfonyl chloride was added to react, and the reaction was tracked by TLC. After the reaction was finished, the reaction solution was concentrated and purified through a neutral alumina column. The eluent was dichloromethane:methanol (120:1, 80:1 were used for elution, respectively), and the white powder product 117.5 was separated and purified. mg (about 0.17 mmol), melting point: 208.1-209.9°C, yield 94.4%. Product analysis and characterization: 1 H NMR (400MHz, CDCl 3 )δ7.40(dd, J=8.2,1.9Hz,1H),7.15(dd,J=8.2,2.5Hz,1H),6.85(d,J=7.7Hz,2H),6.81(dd,J=8.3 ,2.5Hz,1H),6.56(s,1H),6.46(s,1H),6.40(s,1H),6.33(dd,J=8...

Embodiment 2

[0057] Dissolve 100.0 mg of fangchinoline base (about 0.18 mmol) in 3 mL of chloroform, add it into a two-necked flask filled with argon, and place it in a cold well with temperature controlled to -20 ° C. Under magnetic stirring, add the dissolved Add 5.0 mg (about 0.20 mmol) of NaH in 2 mL of chloroform, mix for 1 h, add 23.2 mg (about 0.18 mmol) of ethylsulfonyl chloride to react, and track the reaction by TLC. After the reaction was finished, the reaction solution was concentrated and purified through a neutral alumina column. The eluent was dichloromethane:methanol (eluted at 120:1 and 80:1 respectively), separated and purified to obtain a white powdery product 113.6 mg (about 0.162 mmol), melting point: 205.5-207.2°C, yield 90.0%. Product analysis and characterization: 1 H NMR (400MHz, CDCl 3 )δ7.36(dd, J=8.2,1.9Hz,1H),7.14(dd,J=8.2,2.4Hz,1H),6.82(dt,J=8.3,5.3Hz,3H),6.51(d,J =16.7Hz,2H),6.42–6.30(m,2H),6.04(s,1H),3.92(s,3H),3.88–3.81(m,1H),3.81–3.73(m,3H),3.69( s,1H)...

Embodiment 3

[0059] Dissolve 100.0mg fangchinoline base (about 0.18mmol) in 10mL of dichloromethane, add it into a two-necked flask filled with argon, and place it in a cold well with temperature controlled to 0°C. 62.0 mg (about 0.72 mmol) of piperidine in dichloromethane was mixed for 1 hour, then 25.6 mg (about 0.20 mmol) of n-propylsulfonyl chloride was added to react, and the reaction was tracked by TLC. After the reaction, the reaction solution was concentrated to 1 / 3 of the volume of the original solution, crystallized in a cold well at 0°C for more than 4 hours, filtered quickly, and dried in vacuum below 50°C to obtain 115.9 mg (about 0.162 mmol) of a white powder product. Melting point: 204.9-206.5°C, yield 90.0%. Product analysis and characterization: 1 H NMR (400MHz, CDCl 3 )δ7.29(dd, J=8.2,1.9Hz,1H),7.06(dd,J=8.1,2.4Hz,1H),6.74(dt,J=8.3,5.4Hz,3H),6.43(d,J =14.0Hz,2H),6.36–6.19(m,2H),5.96(s,1H),3.84(s,3H),3.76(dd,J=11.1,5.3Hz,0H),3.73–3.65(m, 3H), 3.62(d, J=9.7Hz, 0H), 3.40...

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Abstract

The invention discloses a sulfonyl fangchinoline compound as well as a preparation method and application thereof. The sulfonyl fangchinoline compound has a structure as shown in a formula (I) or a formula (I'). According to the formula (I) or formula (I'), R is selected from alkyl, aryl, benzyl, heterocyclyl, substituted alkyl, substituted aryl, substituted benzyl and substituted heterocyclyl; the substituent group of the substituted alkyl is halogen or nitro; the substituent group of the substituted aryl, the substituent group of the substituted benzyl and the substituent group of the substituted heterocyclyl are one or more of halogen, alkyl and nitro; Y is selected from one-molecule inorganic acid and organic acid or two-molecule inorganic acid and organic acid. The compound has a bisbenzylisoquinoline parent nucleus structure, has sulfonyl characteristics, has a good XOD inhibition effect, and can be used for treating and improving gout, reducing uric acid and the like.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a sulfonyl fangchinoline base compound and a preparation method and application thereof. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Uric acid is the final product of purine metabolism through XOD. The generation, absorption, decomposition and excretion of uric acid in the human body are in a steady state balance. Once any of the above processes is disturbed, it will lead to the steady state balance of uric acid in the body. Abnormalities occur, which in turn can cause hyperuricemia. [0004] XOD plays a key role in the synthesis of uric acid. Inhibiting the activity of XOD can re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D491/18A61K31/4748A61P19/06
CPCC07D491/18A61P19/06
Inventor 刘玉法吕绪涛高修正闫新华
Owner SHANDONG NORMAL UNIV
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