Amide compound and application thereof in preparing monoamine oxidase inhibitor

An amide compound, monoamine oxidase technology, applied in organic chemistry, drug combination, medical preparations containing active ingredients, etc., can solve the problems of psychotic episodes, side effects, liver toxicity, etc., and achieves improved selectivity, stable properties, and operation. Ease of the process

Inactive Publication Date: 2012-02-29
日照新睿招商发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in addition to inhibiting monoamine oxidase, these drugs also have inhibitory effects on liver drug-metabolizing enzymes. They have many side effects, can produce central excitement, induce psychosis, have liver toxicity, and cause orthostatic hypotension.

Method used

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  • Amide compound and application thereof in preparing monoamine oxidase inhibitor
  • Amide compound and application thereof in preparing monoamine oxidase inhibitor
  • Amide compound and application thereof in preparing monoamine oxidase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Reaction formula:

[0035]

[0036] Method:

[0037] (1) Dissolving the phenolic compound (II) in DMF solvent, then adding NaOH and 2-chloroacetamide, and heating at 85°C for about 6 hours. The amount of phenolic compound: 2-chloroacetamide: NaOH is 5mmol: 5mmol: 7.2mmol, and the volume of DMF is 10ml.

[0038] (2) Dilute the amide compound constructed in step (1) with DMSO solvent to a concentration of 100 μM, pipette 4 μL of the diluent and add it to the reaction well of a 96-well plate, then add 400 μL of pH8.4 boric acid buffer and 4 μL of BSA, and add MAO -A (20mg / mL) or MAO-B (20mg / mL) 4μL, the mixture was reacted at 38°C for 3h, and then the fluorescent probe 4-methyl-7-(3-aminopropyl)-coumarin 2μL ( 10mmol / mL), then react at 38°C for 2h, and use a fully functional spectrofluorometer (λ ex / λ em =365 / 460nm) for detection, judge the level of inhibitory activity of amide compounds on monoamine oxidase according to the level of fluorescence value: the stronge...

Embodiment 2

[0043]Example 2: Preparation of 2-(4-((propene-2-imino)methyl)phenoxy)acetamide (II-1)

[0044]

[0045] The synthetic route is as follows:

[0046]

[0047] 4-Hydroxybenzaldehyde (6mmol), NaOH (7.2mmol) and DMF (10ml) were added to a 50ml round-bottomed flask. After the dissolution was complete, 2-chloroacetamide (5mmol) was added and stirred at 85°C for 6h, the reaction was complete After 3*20ml dichloromethane extraction, NaHCO 3 Washed with saturated solution, dried over anhydrous magnesium sulfate, filtered, sucked dry, purified by column chromatography to obtain a white solid powder with a yield of 91%. Dissolve the obtained white powder in dichloromethane, add one equivalent of propargyl amine and react for one hour, extract with 3*20ml dichloromethane, NaHCO 3 Washed with saturated solution, dried over anhydrous magnesium sulfate, filtered, sucked to dryness, and purified by column chromatography to obtain a white solid product with a yield of 85%. Compound Ch...

Embodiment 3

[0048] Example 3: Preparation of 2-(4-((propene-2-imino)methyl)phenoxy)acetamide (II-2)

[0049]

[0050] The synthetic route is as follows:

[0051]

[0052] 2-Hydroxybenzaldehyde (6mmol), NaOH (7.2mmol) and DMF (10ml) were added to a 50ml round-bottomed flask. After the dissolution was complete, 2-chloroacetamide (5mmol) was added and stirred at 85°C for 6h, the reaction was complete After 3*20ml dichloromethane extraction, NaHCO 3 Washed with saturated solution, dried over anhydrous magnesium sulfate, filtered, sucked to dryness, and purified by column chromatography to obtain a white solid powder with a yield of 88%. Dissolve the obtained white powder in dichloromethane, add one equivalent of propargyl amine and react for one hour, extract with 3*20ml dichloromethane, NaHCO 3 Washed with saturated solution, dried over anhydrous magnesium sulfate, filtered, sucked to dryness, and purified by column chromatography to obtain a white solid product with a yield of 74%. ...

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PUM

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Abstract

The invention provides a new amide compound shown as structural formula (I) and application thereof in preparing monoamine oxidase inhibitor. The invention takes phenols compound shown as formula (II) and 2-chloroacetamide shown as formula (III) as reaction substrate, reaction is taken place to obtain amide compound shown as the formula (I), and then fluorescence detection method is used for detecting monoamine oxidase inhibition activity. The method has simple operation process, raw materials are available, and the obtained monoamine oxidase inhibitor has stable properties, and purity is high (more than 99%); compared with the previously researched method of monoamine oxidase inhibitor, the sieved novel amide monoamine oxidase inhibitor has simple structure, and inhibition activity and selectivity on MAO-A and MAO-B are all greatly improved.

Description

(1) Technical field [0001] The invention provides an application of a class of amide compounds in the preparation of monoamine oxidase inhibitors and a new amide compound with monoamine oxidase inhibitory activity. (2) Background technology [0002] Monoamine oxidase (monoamine oxidase, MAO) is an enzyme that catalyzes the oxidative deamination reaction of monoamine and can inactivate catechin neurotransmitters, and can be used as an antidepressant drug. [0003] Existing monoamine oxidase inhibitors are mainly some hydrazine and non-hydrazine compounds, which inhibit monoamine oxidase and exhibit antidepressant effects, including hydrazine-type phenelzine, isocarbazine, niramide, and non-hydrazine-type transphenylene ring Propylamine etc. This type of drug inhibits monoamine oxidase, reduces the metabolic inactivation of catecholamines, increases the content of catecholamines in synaptic sites, produces antidepressant effects, and has antihypertensive effects. However, in...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/165A61K31/4164A61K31/235A61K31/167A61P25/24C07C251/16C07C235/06C07D233/22
Inventor 朱勍宋明贵
Owner 日照新睿招商发展有限公司
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