(2E)-3-phenyl-N-[2,2,2-trichlorine-1-[[(8-quinolyl amino) thiomethyl]amino]ethyl]-2-acrylamide and medicinal uses thereof

A technology of medicinal salt and medicine, applied in (2E)-3-phenyl-N-[2,2,2-trichloro-1-[[(8-quinolylamino)thiomethyl] Amino]ethyl]-2-acrylamide and its medical application field can solve the problems of low selectivity and targeting

Active Publication Date: 2011-11-16
GENERAL HOSPITAL OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, the types and quantities of drugs for anti-apoptosis and cell protection available for clinical application are still very small, and their selectivity and targeting are not high. Cellular drugs, especially those with a new mechanism of action, are of great significance

Method used

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  • (2E)-3-phenyl-N-[2,2,2-trichlorine-1-[[(8-quinolyl amino) thiomethyl]amino]ethyl]-2-acrylamide and medicinal uses thereof
  • (2E)-3-phenyl-N-[2,2,2-trichlorine-1-[[(8-quinolyl amino) thiomethyl]amino]ethyl]-2-acrylamide and medicinal uses thereof
  • (2E)-3-phenyl-N-[2,2,2-trichlorine-1-[[(8-quinolyl amino) thiomethyl]amino]ethyl]-2-acrylamide and medicinal uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1 : An experimental study on the protection of endoplasmic reticulum stress apoptosis in cardiomyocytes

[0041] Animals: Newborn Wistar rats, within 24 hours of age, male or female

[0042] Isolation and culture of cardiomyocytes :

[0043] Isolation and culture of cardiomyocytes refer to the method of differential adhesion separation (Kreider, A.Messing, H.Doan, S.U.Kim, R.P.Lisak and D.E.Pleasure, Enrichment of Schwann cell cultures from neonatal rat sciatic nerve by differential adhesion, Brain Res 2 (1981), pp.433444.), take newborn Wistar suckling mice within 24 hours to obtain primary cardiomyocytes.

[0044] Effects of Different Concentrations of Compounds of Formula I on the Survival Rate of Cardiomyocytes by MTT Assay

[0045] The isolated primary cultured cardiomyocytes obtained according to the above method were divided into 10 4 Each cell was seeded into a 96-well plate with a volume of 100ul per well (edge ​​wells were filled with sterile ...

Embodiment 2

[0057] Example 2: Detection of apoptosis signal protein expression by Western Blot

[0058] The cardiomyocytes obtained by differential adherence according to the primary cardiomyocyte culture method in Example 1 were prepared according to the ratio of 10 per well. 6 Cells were inoculated into a 6-well plate with a volume of 2ml per well. After culturing in a 37°C, 5% CO2 incubator for 4 days, each group was intervened with the compound of formula I according to the experimental design, and continued to be cultured in a 37°C, 5% CO2 incubator. After reaching the design time point, the cells were lysed with SDS loading buffer, bathed in 100°C for 10 minutes, centrifuged at 4°C (12000rpm×10min), and the supernatant was collected. Soak the nitrocellulose membrane in transfer buffer for 15-20 minutes in advance. Load 50 μg protein / lane, separate by 10% polyacrylamide gel SDS-PAGE electrophoresis, then spread the gel in the electrotransfer holder, and install sponge, filter pape...

Embodiment 3

[0064] Example 3 : The effect of formula I compound on TM-induced cardiomyocyte apoptosis

[0065] The primary cardiomyocytes cultured according to the method for culturing primary cardiomyocytes in Example 1 began to be added with tunicamycin (TM) for the intervention experiment at 4 days. The cells were randomly divided into 5 groups: solvent control group (DMSO), TM intervention group (5ug / ml), formula I compound+TM intervention group (10μM+5μg / ml), formula I compound intervention group (20μg / ml+5μg / ml ), the compound intervention group of formula I (40 μg / ml+5 μg / ml).

[0066] Cell apoptosis detected by flow cytometry: After drug intervention for 24 hours, the cells were treated according to the Annexin V-FITC apoptosis kit method, and the cell apoptosis was detected by flow cytometry (BDACScalibur, Becton-Dickinson Company, USA) within 1 hour. 14,000 cells were collected from each sample for analysis, the experiment was repeated 3 times, and the results were averaged...

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Abstract

The invention relates to an acrylamide compound with a structural formula I or an isomer thereof, a pharmaceutical salt thereof and a solvate thereof, and also relates to the compound or the isomer thereof or the pharmaceutical salt thereof and the solvate thereof, a composition of a pharmaceutically acceptable vector, an excipient or a diluent, and uses of the compound or the composition in preventing and / or treating diseases or symptoms which relate to cardiomyocyte apoptosis and include but are not limited to the uses of (i) treating hungry myocardial atrophy, (ii) treating myocarditis, (iii) treating cardiac failure, (iv) treating or relieving myocardial damage caused by essential hypertension, (v) treating or relieving myocardial damage caused by early-stage acute myocardial infarction, (vi) treating or relieving myocardial damage caused by acute myocardial infarction reperfusion, (vii) treating or relieving cardiomyocyte pathology caused by heart transplant, (viii) treating or relieving dysplastic cardiomyopathy, cardiomyocyte apoptosis caused by anoxia, or improving cardiovascular system sclerosis.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, specifically, the present invention relates to a novel acrylamide compound (2E)-3-phenyl-N-[2,2,2-trichloro-1-[[(8-quinoline Base amino) thiomethyl] amino] ethyl] -2-acrylamide and its pharmaceutical composition, the present invention also relates to said compound and its pharmaceutical composition for anti-apoptosis, prevention or treatment and apoptosis Use for related diseases or symptoms, especially for protecting cardiomyocytes and preventing or treating diseases or symptoms related to cardiomyocyte apoptosis. Background technique [0002] Apoptosis generally refers to a kind of programmed cell death that occurs during the development of cells in the body or under the action of certain factors through the regulation of intracellular genes and their products. Apoptosis is ubiquitous in the biological world, and occurs in both physiological and pathological conditions. It plays an ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/40A61K31/4706A61P9/00A61P9/04A61P9/10A61P9/12
Inventor 何昆仑李松王莉莉李鑫钟武胡国梁王捷李蕊君刘春蕾肖军海龙隆李薇
Owner GENERAL HOSPITAL OF PLA
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