Inhibitor for monoamine oxidase A

A monoamine oxidase and inhibitor technology, applied in the field of monoamine oxidase A inhibitor and its synthesis, can solve the problems of ruthenium tetroxide instability, high price, high toxicity, etc., achieve good monoamine oxidase A inhibitory activity, simple operation process, and subsequent treatment simple effect

Active Publication Date: 2020-01-03
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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  • Inhibitor for monoamine oxidase A
  • Inhibitor for monoamine oxidase A
  • Inhibitor for monoamine oxidase A

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 an inhibitor for monoamine oxidase A. The inhibitor for the monoamine oxidase A is obtained by using cheap ruthenium / carbon as a catalyst to catalyze thioether synthesis at room temperature. The method specifically comprises the following steps: by taking a compound represented by a formula (III) shown in the specification as a reaction raw material, the Ru / C as the catalyst, NaIO4 as an oxidizing agent and water as a solvent, performing a reaction at room temperature, and after the reaction is finished, carrying out post-treatment on the reaction solution to obtain thesulfone compound represented by a formula (IV) shown in the specification. According to the method, the water is used as the solvent, the cheap ruthenium / carbon is oxidized by sodium periodate to generate ruthenium tetroxide, so that the thioether compound is further oxidized to synthesize the target product, and the preparation method is more efficient, faster, more environmentally friendly andmilder; and the prepared inhibitor for the monoamine oxidase A has good monoamine oxidase A inhibition activity, can be used for preparing drugs for inhibiting the activity of the monoamine oxidase A,has a wide application prospect in drug development, and is expected to provide a more effective way for 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 Applications(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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