Sulfonyl tetragonolin base compound and 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: 2022-07-15
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 tetragonolin base compound and preparation method and application thereof
  • Sulfonyl tetragonolin base compound and preparation method and application thereof
  • Sulfonyl tetragonolin base compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Dissolve 100.0 mg of tetrandrine base (about 0.18 mmol) in 3 mL of dichloromethane, add it to a two-necked flask filled with argon, and place it in a cold well with a temperature controlled to 0 °C, add it and dissolve it in 2 mL under magnetic stirring. 66.5 mg (about 0.72 mmol) of triethylamine in dichloromethane, after mixing for 1 h, 31.0 mg (about 0.27 mmol) of methanesulfonyl chloride was added to react, and the reaction was followed by TLC. After the reaction, the reaction solution was concentrated and purified by passing through a neutral alumina column. The eluent was dichloromethane: methanol (eluted at 120:1 and 80:1, respectively), and separated and purified to obtain a white powdery product 117.5 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...

Embodiment 2

[0057] Dissolve 100.0 mg of tetrandrine base (about 0.18 mmol) in 3 mL of chloroform, add it to a two-necked flask filled with argon, and place it in a cold well whose temperature is controlled to -20°C. Under magnetic stirring, add the solvent. After mixing 5.0 mg (about 0.20 mmol) of NaH in 2 mL of chloroform for 1 h, 23.2 mg (about 0.18 mmol) of ethylsulfonyl chloride was added to react, and the reaction was followed by TLC. After the reaction was completed, the reaction solution was concentrated and purified by passing through a neutral alumina column. The eluent was dichloromethane: methanol (eluted at 120:1 and 80:1, respectively), and 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,1...

Embodiment 3

[0059] Dissolve 100.0 mg of tetrandrine base (about 0.18 mmol) in 10 mL of dichloromethane, add it to a two-necked flask filled with argon, and place it in a cold well controlled to a temperature of 0 °C, add it and dissolve it in 2 mL under stirring. 62.0 mg (about 0.72 mmol) of piperidine in dichloromethane, after mixing for 1 h, 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, quickly filtered, and vacuum-dried below 50°C to obtain 115.9 mg (about 0.162 mmol) of white powdery 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...

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Abstract

The invention discloses a sulfonyl tetragonolin base compound, a preparation method and application thereof, and the compound has a structure represented by formula (I) or formula (I'): wherein, R is selected from hydrocarbon group, aromatic hydrocarbon group, benzyl group, heterocycle base, substituted hydrocarbon group, substituted aromatic hydrocarbon group, substituted benzyl group, substituted heterocyclic group; wherein, the substituent group of the substituted hydrocarbon group is halogen or nitro, the substituent group of the substituted aromatic hydrocarbon group, the substituent group of the substituted benzyl group, the substituted heterocyclic group The substituent group of the cyclic group is one or more of halogen, alkyl and nitro; Y is selected from 1 molecule of inorganic acid, organic acid or 2 molecules of inorganic acid and organic acid. The compounds have a bisbenzylisoquinoline core structure and a sulfonyl character, and have a good XOD inhibitory effect, and can be used for the treatment and improvement of gout, lowering uric acid and other applications.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a sulfonyl tetragonolin base compound and a preparation method and application thereof. Background technique [0002] The information disclosed in this Background section is only for enhancement of understanding of the general background of the invention and should not necessarily be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person of ordinary skill in the art. [0003] Uric acid is the final product of purine metabolism by XOD. The production, absorption, decomposition and excretion of uric acid in the human body are in a steady state balance. Once a disorder occurs in one of the above processes, it will lead to the steady state balance of uric acid in the body. An abnormality occurs, which in turn leads to hyperuricemia. [0004] XOD plays a key role in the synthesis of uric acid. Inhibiting the activity of XOD ca...

Claims

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Application Information

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Patent Type & Authority Patents(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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