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Naphthyridine derivative and application thereof as monoamine oxidase inhibitor

A use, technology of naphthyridine, applied in the field of naphthyridine derivatives and monoamine oxidase inhibitors, to achieve the effect of reducing side effects

Pending Publication Date: 2022-05-06
SHENZHEN CHILDRENS HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, MAO inhibitors have generally been associated with a number of side effects that have generally limited their applicability and tolerability

Method used

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  • Naphthyridine derivative and application thereof as monoamine oxidase inhibitor
  • Naphthyridine derivative and application thereof as monoamine oxidase inhibitor
  • Naphthyridine derivative and application thereof as monoamine oxidase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] The preparation of embodiment 1 compound I-1

[0031]

[0032] Step 1): Under nitrogen atmosphere, add 3,4,5-trimethoxybenzoic acid (4.24g, 0.02mol) and 40ml benzene into the reaction kettle, stir to dissolve, and then add SOCl 2 (7.15g, 0.06mol), react at 70-80°C for 6 hours, after the reaction, recover benzene by distillation under reduced pressure, and remove excess SOCl at the same time 2 , directly used in the next reaction without purification;

[0033] Step 2): Under nitrogen atmosphere, add 2-hydroxy-1,5-naphthyridine (3.21g, 0.22mol) and 50ml tetrahydrofuran into the reaction kettle, stir and dissolve, then slowly add the 3,4, 5-Trimethoxybenzoyl chloride tetrahydrofuran solution (20ml) was added dropwise in half an hour, and reacted overnight at room temperature. After the reaction was detected by TLC, tetrahydrofuran was recovered by distillation, and the residue was washed with dichloromethane solution and 10% aqueous sodium carbonate solution, then was...

Embodiment 2-3

[0035] The preparation of embodiment 2-3 compound I-2 and I-3

[0036] Referring to the method of Example 1, compounds I-2 and I-3 were prepared, and their structure confirmation data are as follows:

[0037]

[0038]

Embodiment 4

[0039] The inhibitory activity of embodiment 4 compound I to monoamine oxidase A and B

[0040]Use 100mM pH 7.4 potassium phosphate buffer to make recombinant human MAO-A into 12.5 μg / mL sample solution, and MAO-B into 75 μg / mL sample solution. Add 20 μL of the test compound solution and 80 μL of monoamine oxidase to a black 96-well plate, mix well, incubate at 37°C in a dark place for 15 minutes, add 200 μM Amplex Red reagent, 2U / mL horseradish peroxidase, 2mM p-hydroxyphenylethylamine (inhibit MAO-A) or 2mM benzylamine (inhibit MAO-B) to initiate the reaction, incubate at 37°C for 20min, measure the fluorescence emission intensity at 590nm on a multi-functional microplate reader with a fixed excitation wavelength of 545nm, buffer with potassium phosphate solution instead of MAO-A or MAO-B as blank; the formula for the inhibitory rate of monoamine oxidase inhibition by the compound is: 100-(IFi) / (IFc)*100, where IFi and IFc are the presence of inhibitors and no inhibitors res...

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PUM

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Abstract

The invention relates to a naphthyridine derivative which can be used for inhibiting monoamine oxidase (MAO), and particularly can be used for selectively inhibiting MAO-B. The compound has development and application prospects, and can be used for treating brain injury, cerebral apoplexy, traumatic brain injury, anxiety disorder, mood disorder, autism, vascular dementia, Alzheimer's disease and other diseases.

Description

technical field [0001] The invention relates to a naphthyridine derivative and its use as a monoamine oxidase inhibitor. Background technique [0002] Monoamine oxidase (Monoamine oxidase, MAO) is a very important enzyme in organisms, its function is to oxidize and metabolize some monoamines in brain and peripheral nervous tissue. According to the different selectivity of the enzyme to the substrate, MAO can be divided into two types: MAO-A and MAO-B. The main difference between the two is in the selectivity to the substrate and the sensitivity to the inhibitor. The former is mainly distributed in the placental tissue, adipose tissue, thyroid and lung, and less distributed in the brain. ,epinephrine, AD) has a high affinity; the latter is mainly distributed in various parts of the central nervous system: hypothalamus, prefrontal cortex, amygdala, spinal cord, etc., and also in the uterus, kidney, liver and heart, for benzylamine and Non-polar aromatic amines such as pheny...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04A61K31/4375A61P9/10A61P25/00A61P25/22A61P25/28A61P25/16
CPCC07D471/04A61P9/10A61P25/00A61P25/22A61P25/28A61P25/16
Inventor 谭回
Owner SHENZHEN CHILDRENS HOSPITAL
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