A novel ion channel inhibitor and its synthesis process

Abstract

This invention discloses a novel ion channel inhibitor and its synthesis process, belonging to the field of pharmaceutical preparation technology. The novel ion channel inhibitor and its synthesis process include: Step 1, injecting raw materials into a reaction vessel, injecting lithium hydroxide, injecting a tetrahydrofuran / water mixture, and refluxing to collect reactant A; Step 2, adding cobalt chloride to reactant A, drying dichloromethane, and refluxing to obtain reactant B. This novel ion channel inhibitor and its synthesis process have several advantages. First, the S-C bond is longer than the C-C bond, making it larger in size than adamantane. The three sulfur groups also possess a certain degree of spatial aromaticity, leading to better interaction with proteins. Preliminary experiments have shown that it may have an inhibitory effect 200 times stronger than adamantane. Second, the in vivo metabolism and environmental degradation rate of sulfur are much higher than that of hydrocarbons, therefore its toxicity and the induction of drug resistance are lower.

Description

Technical Field

[0001] This invention relates to the field of drug preparation technology, specifically to a novel ion channel inhibitor and its synthesis process. Background Technology

[0002] Influenza A virus particles undergo endocytosis through the interaction of surface glycoproteins and the mucosa, forming intracellular vesicle-like endosomes. This process facilitates lysosomal dissolution. Acidic protons from the lysosomes pass through the M2 protein ion channel of the virus particle into the space between the viral capsid and phospholipid membrane, dissolving the capsid and releasing the viral genome into the cell for replication. The amino group of adamantane is protonated at neutral pH, and adamantane acts like a plug. The acidified adamantane enters the M2 ion channel and blocks it, thus interfering with viral entry into the cell and preventing viral uncoating and nucleic acid release. It is an effective inhibitor of influenza A virus, and experimental evidence suggests that it can inhibit viral entry into the cell. During the later stages of viral replication, amantadine interferes with the higher-order protein structure of hemagglutinin, thereby inhibiting the assembly of the viral protein shell. The United States approved amantadine as a preventive drug for influenza A in 1966, and confirmed it as a therapeutic drug in 1976, building upon its preventive use. The efficacy and safety of this drug in adult patients have been widely recognized. Amantadine can specifically enter the M2 ion channel of viral particles, inhibiting influenza A virus, and is used for the prevention and treatment of influenza A. The mechanism of action for other ion channels is not fully understood. In Japan, amantadine was used as a treatment for Parkinson's disease until it was approved for the treatment of influenza A virus infection in 1998.

[0003] Amantadine is overused in the aquaculture industry as an antibiotic. Due to its metabolic and environmental instability, viruses have developed resistance. The dosage is constantly increasing, causing side effects on organs with biological ion channels such as the liver, brain, and heart. The problem this invention aims to solve is to develop a more effective, safer, and less resistant inhibitor of biological ion channels. One possible indication for this inhibitor-based drug is seasonal avian influenza A virus, with the target being the virus's M2 ion channel. Currently, the main inhibitors of the M2 ion channel are amantadine and its derivatives. Due to the chemical stability of the adamantyl group, it is not easily metabolized in vivo or degraded in the environment, leading to the development of drug resistance in viruses. Summary of the Invention

[0004] The purpose of this invention is to provide a novel ion channel inhibitor and its synthesis process. This novel ion channel inhibitor and its synthesis process have several advantages. First, the SC bond is longer than the CCC bond, and it is larger in size than adamantane. The three sulfur groups also possess a certain degree of spatial aromaticity, leading to better interaction with proteins. Preliminary experiments have shown that it may be 200 times more potent than adamantane in its inhibitory effect. Second, the in vivo metabolism and environmental degradation rate of sulfur are much higher than that of hydrocarbons, therefore its toxicity and the likelihood of inducing drug resistance are lower.

[0005] To achieve the above effects, the present invention provides the following technical solution: a novel ion channel inhibitor, comprising: the ion channel inhibitor comprising trithionane.

[0006] The synthetic process for manufacturing the above-mentioned novel ion channel inhibitor includes:

[0007] Step 1: Inject the raw materials into the reactor, inject lithium hydroxide, inject tetrahydrofuran / water mixture, and reflux to collect reactant A.

[0008] Step 2: Add cobalt chloride to reactant A, dry dichloromethane and reflux to obtain reactant B.

[0009] Step 3: Add sodium azide and water to reactant B, cool with anhydrous acetone, and obtain reactant C.

[0010] Step 4: Add tetrahydrofuran to reactant C and heat to recover the gas and obtain reactant D.

[0011] Step 5: Add reactant D to a mixture of hydrogen chloride and tetrahydrofuran / water.

[0012] Step 6: Prepare trisulfide adamantane.

[0013] Furthermore, in step one, the molecular formula of the raw material is C9H. 12 O2S3.

[0014] Furthermore, in step one, the mixing ratio of tetrahydrofuran / water is 3:1.

[0015] Furthermore, in step one, the raw material is mixed with lithium hydroxide in a ratio of 1:10.

[0016] Furthermore, in step two, the molecular formula of reactant A is C8H. 10 O2S 3。

[0017] Furthermore, in step three, the molecular formula of reactant B is C8H9OS3CL.

[0018] Furthermore, in step four, the molecular formula of reactant C is C8H9OS3N. 3。

[0019] Furthermore, in step five, the molecular formula of reactant D is C8H9OS3N.

[0020] Furthermore, in step six, the concentration of the finished trisulfide adamantane is 85%.

[0021] This invention provides a novel ion channel inhibitor and its synthesis process, which has the following beneficial effects:

[0022] This novel ion channel inhibitor and its synthesis process have several advantages. First, the SC bond is longer than the C-C bond, and it is larger in size than adamantane. The three sulfur groups also have a certain degree of spatial aromaticity, which allows for better interaction with proteins. Preliminary experiments have shown that it may be 200 times more effective than adamantane in inhibiting protein activity. Second, sulfur has a much higher rate of metabolism in vivo and degradation in the environment than hydrocarbons, so its toxicity and the induction of drug resistance are likely to be lower. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of the synthesis process of the present invention;

[0024] Figure 2 This is a schematic diagram of the NMR hydrogen spectrum of the finished product of this invention;

[0025] Figure 3 This is a schematic diagram of the NMR carbon spectrum of the finished product of this invention;

[0026] Figure 4 This is a schematic diagram of the infrared spectrum of the finished product of the present invention. Detailed Implementation

[0027] This invention provides a technical solution:

[0028] Example 1, please refer to Figures 1-4 A novel ion channel inhibitor, comprising: ion channel inhibitors including adamantane trisulfide,

[0029] The synthetic process for manufacturing a novel ion channel inhibitor as described above includes: Step 1, injecting raw materials into a reaction vessel, including lithium hydroxide (which plays an important role in the pharmaceutical industry as a commonly used alkaline catalyst for synthesizing certain drugs and organic compounds; lithium hydroxide is also used to control the pH and solubility of drugs, thereby enhancing drug stability and bioavailability; these properties make lithium hydroxide an indispensable chemical in the pharmaceutical industry), and adding a tetrahydrofuran / water mixture (tetrahydrofuran is a reaction solvent commonly used in chromatographic analysis; it reacts with alkyl alkali metal compounds and aryl alkali metal compounds to form water and molecular complexes, thus enabling chromatographic analysis; the functional group of tetrahydrofuran includes hydrogen ions (H+), therefore it can react with many different compounds, such as alkyl compounds and aryl alkali metals). By using tetrahydrofuran as the reaction solvent... This allows for more accurate analysis of the structure and properties of compounds, thus providing strong support for scientific research and industrial production. The reaction process involves: 1. Retrieving reactant A by reflux. The molecular formula of the raw material is C9H12O2S3. The mixing ratio of tetrahydrofuran / water is 3:1, and the mixing ratio of the raw material and lithium hydroxide is 1:10. 2. Adding cobalt chloride to reactant A, drying dichloromethane, and refluxing, yielding reactant B. The molecular formula of reactant A is C8H10O2S3. 3. Adding sodium azide and water to reactant B, cooling with anhydrous acetone, yielding reactant C. The molecular formula of reactant B is C8H9OS3CL. 4. Adding tetrahydrofuran to reactant C, heating, recovering the gas, yielding reactant D. The molecular formula of reactant C is C8H9OS3N3. 5. Adding hydrogen chloride and a tetrahydrofuran / water mixture to reactant D. The molecular formula of reactant D is C8H9OS3N. 6. Obtaining trisulfide adamantane, with a final product concentration of 85%.

[0030] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A novel ion channel inhibitor, characterized in that, include: The ion channel inhibitors include trithionamide.

2. The synthetic process for manufacturing the novel ion channel inhibitor as described in claim 1, characterized in that, include: S1. Inject the raw materials into the reactor, inject lithium hydroxide, inject tetrahydrofuran / water mixture, and reflux to collect reactant A; S2. Cobalt chloride is added to reactant A, and dichloromethane is dried and refluxed to obtain reactant B; S3. Add sodium azide and water to reactant B, cool with anhydrous acetone, and obtain reactant C. S4. Reactant C is added to tetrahydrofuran and heated to recover the gas and obtain reactant D; S5. Reactant D is added to a mixture of hydrogen chloride and tetrahydrofuran / water; S6. Trithionaneamine was prepared.

3. The synthesis process of a novel ion channel inhibitor according to claim 2, characterized in that, In step S1, the molecular formula of the raw material is C9H. 12 O2S3.

4. The synthesis process of a novel ion channel inhibitor according to claim 2, characterized in that, In step S1, the mixing ratio of tetrahydrofuran / water is 3:

1.

5. The synthesis process of a novel ion channel inhibitor according to claim 2, characterized in that, In step S1, the raw material is mixed with lithium hydroxide in a ratio of 1:

10.

6. The synthesis process of a novel ion channel inhibitor according to claim 2, characterized in that, In step S2, the molecular formula of reactant A is C8H. 10 O2S 3。 7. The synthesis process of a novel ion channel inhibitor according to claim 2, characterized in that, In step S3, the molecular formula of reactant B is C8H9OS3CL.

8. The synthesis process of a novel ion channel inhibitor according to claim 2, characterized in that, In step S4, the molecular formula of reactant C is C8H9OS3N. 3。 9. The synthesis process of a novel ion channel inhibitor according to claim 2, characterized in that, In step S5, the molecular formula of reactant D is C8H9OS3N.

10. The synthesis process of a novel ion channel inhibitor according to claim 2, characterized in that, In step S6, the concentration of the trisulfide adamantane product is 85%.

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