A class of n-benzylaniline derivatives with free radical scavenging effect and their medicinal use

A technology of benzylaniline and free radicals, which is applied in the field of N-benzylaniline derivatives and their pharmaceutical uses, can solve the problems of decreased free radical scavenging ability, decreased benzene ring electron cloud density and the like, and achieves good free radical scavenging activity. Effect

Active Publication Date: 2022-02-11
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chinese Invention 200910129816.3 discloses Teriravone, a cyclic derivative of Edaravone. Since it protects the hydroxyl group of the metabolic site of Edaravone, it is expected to have longer action time and in vivo activity. An electron-withdrawing carbonyl group is introduced on the benzene ring, resulting in a decrease in the electron cloud density on the benzene ring, and a decrease in its ability to scavenge free radicals (Appendix 1)

Method used

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  • A class of n-benzylaniline derivatives with free radical scavenging effect and their medicinal use
  • A class of n-benzylaniline derivatives with free radical scavenging effect and their medicinal use
  • A class of n-benzylaniline derivatives with free radical scavenging effect and their medicinal use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] The synthesis of embodiment 1 target compound:

[0020] 1.1 Synthesis of target compound 1:

[0021] synthetic route:

[0022]

[0023] Add raw material A (4.3g, 20mmol) and 3,5-dichlorosalicylaldehyde (3.9g, 20mmol) in a 250mL eggplant-shaped bottle, add 100mL methanol, heat and reflux for 12h, filter, and dry the filter cake to obtain Imine light red solid 2.2g, add 50mL methanol, imine (2.2g) in 250mL eggplant-shaped bottle, add sodium borohydride (1.0g) in 5 batches, after TCL detects that the reaction is complete, adjust the pH with concentrated HCl to 7 or so, add water 100mL, a pale yellow solid precipitates out, filter with suction, take the filter cake, and dry to obtain 1.6 g of a pale yellow solid, with a yield of 72.4%. 1 H NMR(400MHz,DMSO-d6)δ9.72(s,1H),7.62(s,1H),7.60(t,1H),7.46(d,1H),7.25(d,1H),6.70(s, 1H), 6.51(d, 1H), 5.55(s, 1H), 4.36(d, 2H), 2.39(s, 3H). 13 C NMR (101MHz, DMSO-D6) δ160.65, 156.98, 155.80, 150.86, 150.24, 141.64, 129.97, 128.11,...

Embodiment 2

[0042] Embodiment 2 target compound anti-DPPH free radical test

[0043] Diphenylpicryl radical (DPPH) is a convenient method for screening antioxidants. When excess free radical scavenger exists, its remaining concentration can reflect the free radical scavenging ability of the target substance, the smaller the remaining concentration, the greater the free radical scavenging ability.

[0044] Accurately weigh 39.4mg of DPPH, place it in a 100mL volumetric flask, and dilute it to 100mL with 95% ethanol to make a DPPH solution (1.0mmol / L). The target compound is prepared as a 1.0mmol / L solution with DMF as a solvent .

[0045] 1.0mL of DPPH solution and 4.0mL of the target compound solution were placed in a 10mL volumetric flask, and the volume was adjusted to 10mL with water, and left for 3 hours, and the concentration of remaining DPPH was measured by high performance liquid phase method (detection wavelength: 517nm).

[0046] The concentration (mmol / L) of the residual DPPH...

Embodiment 3

[0049] Example 3 The protective effect of the target compound on the injury of primary cortical neurons cultured in vitro (glutamic acid model)

[0050] After the primary neurons were cultured for 9 days, they were pre-administered for 30 minutes and incubated for 45 minutes with 50 μmol of glutamate + 10 μmol of glycine. The liquid was changed in full amount (drugs and glutamic acid glycine were all withdrawn), and the LDH leakage rate was measured after 8 hours.

[0051] After the primary cortical neurons were given various treatments, the neuron culture medium in the six-well plate was drawn into a 1.5mL plastic centrifuge tube for later use; the cells were washed with PBS solution 3 times, 1000 μL of PBS was added to each well, and the cells were repeatedly frozen and thawed for 3 centrifuge at 12,000'g at 4°C for 5 minutes, and absorb the supernatant for later use. Aspirate 50 μL of culture solution and 25 μL of supernatant to measure LDH enzyme activity, and use lactate...

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PUM

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Abstract

A class of N-benzylaniline derivatives with free radical scavenging effect and their medicinal use, the structure conforms to the general formula (I) wherein: R is -Cl, -Br, -F, -C(CH 3 ) 3 or-CF 3 , X is ‑O‑ or ‑NH‑. The drugs have good effects of reducing nerve damage after stroke and promoting functional recovery, and can be used for preparing drugs for treating stroke damage and ischemic nerve function loss caused by it.

Description

technical field [0001] The invention belongs to the field of pharmacy and provides a class of N-benzylaniline derivatives with free radical scavenging function and their medicinal application. Background technique [0002] Cell membrane lipid peroxidation damage, protein oxidation and DNA damage caused by increased harmful reactive oxygen species (ROS) during ischemia or after reperfusion are one of the important causes of cerebral ischemia. Edaravone (EDA) is a free radical scavenger. Clinical studies suggest that N-acetylaspartic acid (NAA) is a specific marker of surviving nerve cells, and its content decreases sharply in the early stage of cerebral infarction. The administration of edaravone to patients in the acute stage of cerebral infarction can inhibit the reduction of local cerebral blood flow around the infarction, and make the NAA content in the brain significantly higher than that of the glycerol control group on the 28th day after the onset. Preclinical studie...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D498/04A61K31/5365A61P25/00
CPCC07D498/04A61P25/00
Inventor 李飞陈冬寅杨磊李元盛周宇董泽中
Owner NANJING MEDICAL UNIV
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