A monoamine oxidase inhibitor

A monoamine oxidase and inhibitor technology, applied in the field of monoamine oxidase A inhibitor and its synthesis, can solve the problems of high price, high toxicity, unstable properties of ruthenium tetroxide, etc., and achieve simple operation process, simple follow-up treatment, good monoamine oxidase A inhibition active effect

Active Publication Date: 2021-05-11
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, ruthenium tetroxide has disadvantages such as unstable properties, high toxicity, and high price, which have certain limitations for chemical research.

Method used

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  • A monoamine oxidase inhibitor
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1: the preparation of ether compound III

[0024] The reaction formula is as follows:

[0025]

[0026] In the reaction flask, add 1.258g (5.0mmol) compound II (purchased from Sigma-Aldrich company) and 1.382g (10.0mmol) potassium carbonate, dissolve with 60mL acetone, start stirring, then add 0.576g (5.0mmol) compound therein I (purchased from Sigma-Aldrich Company), heated and refluxed for 7 hours. The TLC method was used to detect that the reaction of compound II was complete, and the reaction was stopped. The reaction liquid was filtered and washed with dichloromethane (50 mL×2), and the filtrate and washing liquid were combined. Washed twice with saturated sodium chloride solution, dried with anhydrous sodium sulfate, evaporated to remove the solvent, and separated by column chromatography (mobile phase n-hexane: ethyl acetate = 15:1) to obtain the refined compound III with a yield of 77% . The structural representation of compound formula III is ...

Embodiment 2

[0028] Embodiment 2: the preparation of sulfone compound IV

[0029] The reaction formula is as follows:

[0030]

[0031] Add 0.02g Ru / C catalyst, sodium periodate 470mg (2.2mmol) in the reaction bottle, then add 4mL water, then add 285mg (1mmol) compound III in the reaction bottle under stirring state, react at room temperature 2h. The TLC method was used to detect that the reaction of compound III was complete, and the reaction was stopped. The reaction liquid was filtered and washed with dichloromethane (15 mL×2), and the filtrate and washing liquid were combined. Wash twice with saturated sodium chloride solution, dry with anhydrous sodium sulfate, and evaporate the solvent to obtain compound IV with a yield of 99%. The structural representation of compound formula IV is as follows:

[0032] 1 H NMR (500MHz, CDCl 3 )δ8.29-7.60(m,3H),4.27(s,1H),4.20-4.17(m,2H),3.92-3.88(m,2H),3.56-3.53(m,2H),3.27-3.24( m,2H),3.19(s,1H),3.34(s,3H). 13 C NMR (125MHz, CDCl 3 )δ141...

Embodiment 3

[0033] Example 3: Monoamine Oxidase A Inhibitory Activity Test

[0034] (1) Sample preparation

[0035] The compound (IV) prepared in Example 2 was dissolved in dimethyl sulfoxide (DMSO), and prepared into samples with a concentration gradient of 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 mmol / L respectively liquid, denoted as sample 1.

[0036] (2) Compound (IV) test method for monoamine oxidase-A inhibitory activity

[0037] Add 4 μL of monoamine oxidase-A (MAO-A) and 4 μL of sample 1 prepared in step (1) to EP tubes containing 386 μL of boric acid buffer (pH=8.4), mix, and react the mixture in a water bath at 38 °C for 2 h , and then add 2 μL of probe 7-(3-aminopropoxy)-4-methylcoumarin (10 mmol / ml) and 4 μL of bovine serum albumin ( BSA), and the EP tube was placed in a 38°C water bath to continue the reaction for 2h. At the same time, it is necessary to detect the enzyme activity of the enzyme without inhibitor, that is, add 4 μL monoamine oxidase-A (MAO-A) to the EP...

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Abstract

The invention discloses a monoamine oxidase A inhibitor, which is obtained by using cheap ruthenium carbon as a catalyst to catalyze the synthesis of thioether at room temperature, specifically: using the compound represented by formula (III) as the reaction raw material, Ru / C as catalyst, NaIO 4 is an oxidant, water is a solvent, and the reaction is carried out at room temperature. After the reaction is completed, the reaction liquid is post-treated to obtain the sulfone compound shown in formula (IV). The method of the invention uses water as a solvent, oxidizes cheap ruthenium carbon with sodium periodate to generate ruthenium tetroxide, and further oxidizes the sulfide compound to synthesize the target product, and the preparation method is more efficient, quick, environmentally friendly and mild. The prepared monoamine oxidase A inhibitor has good monoamine oxidase A inhibitory activity, can be used to prepare a drug for inhibiting the activity of monoamine oxidase A, and has broad application prospects in drug development, in order to provide a more effective way for the treatment of related diseases.

Description

[0001] (1) Technical field [0002] The invention relates to a monoamine oxidase A inhibitor and its synthesis method and application. [0003] (2) Background technology [0004] Sulfone compounds are very important intermediates in organic synthesis, which are widely used in medicinal chemistry, materials science, and have a wide range of biological activities. For example, bicalutamide (structure a) is an antiandrogen drug, which is suitable for the treatment of advanced prostate cancer; raropiran (structure b) is a commonly used cardiovascular drug for the treatment of lipodystrophy; Cyclooxygenase (structure c) is a selective inhibitor of cyclooxygenase, which can be used to treat arthritis pain relief, has good patient tolerance, and also has the ability to prevent colorectal cancer, esophageal cancer, treat head and neck cancer, breast cancer, Potential clinical value and therapeutic effect of bladder cancer and cervical cancer; Dapsone (structure d) has a certain antiba...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C319/20C07C323/29C07C315/02C07C317/36A61K31/145A61P25/28A61P25/18A61P25/24
CPCA61K31/145A61P25/18A61P25/24A61P25/28C07C315/02C07C317/36C07C319/20C07C323/29
Inventor 王宇光刘贝李静
Owner ZHEJIANG UNIV OF TECH
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