131707-25-0 Usage
Description
Arbidol, or umifenovir, an indole-derivative with broad-spectrum activity against both enveloped and non-enveloped viruses,was initially approved in China and Russia for the treatment of influenza A and B.Arbidol is believed to block the entry of influenza virus (A and B) into the host cells by increasing the stability of the hemagglutinin (HA) and hampering low pH reorganizations necessary for fusion machinery of hemagglutinin with the membrane.Arbidol could interfere with advanced stages of the viral life cycle, in that it is capable of interacting with both viral proteins and lipids.Regarding its structure, the presence of amine in position 4 and the hydroxyl moiety in position 5 is crucial for its antiviral activity. It is reported that 40% of the drug could be excreted unchanged after the administration while its half-life is between 17 and 21h.
Uses
Umifenovir is an intermediate in synthesizing Arbidol Sulfoxide (A766005), a metabolite of Arbidol (A766000) which is a medicinal agent for treating viral infections.
Biological Activity
Arbidol Arbidol is a broad spectrum antiviral. Displays activity against a range of respiratory and hepatitis viruses including influenza A, B and C, adenovirus, and hepatitis B and C. Increases stability of influenza viral hemagglutinins (HA) and prevents low-pH HA transition so inhibiting viral fusion. Also inhibits SARS-CoV-2 infection in vitro (IC50 = 4.11 μM).
Mechanism of action
Probable Mechanism of Actionlt is hypothesized that arbidol inhibits the contact between the virus and host cell that further prevents the entry of the virus into host cells. It is also being predicted that arbidol also interferes with the late stages of virus cycle by interacting with lipids and proteins of the virus which are essential for the viral replication;probably arbidol binds with these essential components that further inhibit viral replication (Boriskin et al., 2008).Umifenovir inhibits membrane fusion.Umifenovir prevents contact between the virus and target host cells. Fusion between the viral envelope (surrounding the viral capsid) and the cell membrane of the target cell is inhibited. This prevents viral entry to the target cell, and therefore protects it from infection.Some evidence suggests that the drug’s actions are more effective at preventing infections from RNA viruses than infections from DNA viruses.As well as specific antiviral action against both influenza A and influenza B viruses, umifenovir exhibits modulatory effects on the immune system. The drug stimulates a humoral immune response, induces interferon-production, and stimulates the phagocytic function of macrophages.https://newdrugapprovals.org
Clinical Use
Arbidol in Treatment of covID-19Although,arbidol is not approved by US-FDA for the treatment of cOVID-19,some pre-clinical and clinical studies have reported that it may be a very efficacious therapeutic molecule for COVID-19 (Deng et al.,2020; Wang et al.,2020).Arbidol has been included in the latest version of the guidelines issued by the National Health Commission (NHC) of the people's republic of China for the prevention, diagnosis, and treatment of novel coronavirus induced pneumonia at the recommended dose of 200 mg, 3 times/day for 10 days for adults (National Health Commission,China).An in-vitro study claimed that arbidol is effective against COVID-19 at the concentration range of 10-30 uM (News: Abidol and darunavir can effectively inhibit corona virus (2020). A retrospective study conducted by Deng and colleagues reported that patients who received oral arbidol plus lopinavir/ritonavir showed improvement in clinical symptoms and reduced viral load as a compared to the patients who received lopinavir/ritonavir alone (Deng et al.，2020).A randomized multi-centre controlled clinical trial of arbidol in the patients with cOVID-19 is currently running in China (ChiCTR2000029573).Besides this, one more study was conducted on 69 patients of COVID-19.In this study, it was reported that the administration of arbidol at the dose of 0.4 g,TID for 9 days improves the discharging rate from the hospital and also decreases the mortality rate of patients (Wang et al.，2020). In addition，another study also reported that arbidol is more superior to the combination therapy of lopinavir/ritonavir (Zhu et al.，2020).Arbidol: a broad-spectrum antiviral compound that blocks viral fusionArbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein
Check Digit Verification of cas no
The CAS Registry Mumber 131707-25-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,1,7,0 and 7 respectively; the second part has 2 digits, 2 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 131707-25:
(8*1)+(7*3)+(6*1)+(5*7)+(4*0)+(3*7)+(2*2)+(1*5)=100
100 % 10 = 0
So 131707-25-0 is a valid CAS Registry Number.
InChI:InChI=1/C22H25BrN2O3S/c1-5-28-22(27)20-18(13-29-14-9-7-6-8-10-14)25(4)17-11-16(23)21(26)15(19(17)20)12-24(2)3/h6-11,26H,5,12-13H2,1-4H3
131707-25-0Relevant articles and documents
Method for synthesizing arbidol hydrochloride intermediate
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Paragraph 0015, (2020/08/25)
The invention discloses a method for synthesizing an arbidol hydrochloride intermediate, and belongs to the technical field of medical intermediates. According to the method, 5-hydroxy-1, 2-dimethylindole-3-carboxylic acid ethyl ester is used as a raw material, and esterification, bromination, thiophenol and deprotection, Mannich reaction and salification are performed to obtain arbidol hydrochloride. In the process of generating the most important intermediate 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylic acid through bromination reaction, (p-methyl isopropyl benzene)-rutheniumdichloride dimer is used as a catalyst, NBS serves as a bromination reagent, DMA serves as a solvent to replace a traditional bromine bromination reagent, reaction conditions are mild, reaction selectivity is high, raw material sources are convenient, pollution of bromine to the environment can be avoided, and the catalytic activity of the novel catalyst is not reduced due to the influence of thereaction environment. Therefore, the method has the advantages of few byproducts, high yield, low production cost, high safety, energy conservation and the like, and meets the modern chemical production requirements of green reaction.
Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin
Wright, Zo? V.F.,Wu, Nicholas C.,Kadam, Rameshwar U.,Wilson, Ian A.,Wolan, Dennis W.
supporting information, p. 3744 - 3748 (2017/07/27)
Influenza is a highly contagious respiratory viral infection responsible for up to 50,000 deaths per annum in the US alone. The need for new therapeutics with novel modes of action is of paramount importance. We determined the X-ray structure of Arbidol with influenza hemagglutinin and found it was located in a distinct binding pocket. Herein, we report a structure-activity relationship study based on the co-complex combined with bio-layer interferometry to assess the binding of our compounds. Addition of a meta-hydroxy group to the thiophenol moiety of Arbidol to replace a structured water molecule in the binding pocket resulted in a dramatic increase in affinity against both H3 (1150-fold) and H1 (98-fold) hemagglutinin subtypes. Our analogues represent novel leads to yield more potent compounds against hemagglutinin that block viral entry.
Indole derivative having antiviral, interferon-inducing and immunomodulatory effects
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, (2008/06/13)
A novel compound--ethyl 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole-3- carboxylate hydrochloride monohydrate having the following formula: STR1 A process for preparing the compound according to the invention, characterized in that it comprises treating ethyl 5-acetoxy-1,2-dimethylindole-3-carboxylate with a brominating agent in an inert organic solvent under reflux, reacting the resultant ethyl 5-acetoxy-6-bromo-2-bromomethyl-1-methylindole-3-carboxylate with thiophenol in the presence of an alkali metal hydroxide or its alcoholate in an organic solvent, reacting the resultant ethyl 6-bromo-5-hydroxy-1-methyl-2-phenylthiomethylindole-3-carboxylate with an aminomethylating agent in an organic solvent at a temperature of from 65° C. to a temperature of refluxing the reaction mixture. The end product is then isolated from the resultant base--ethyl 6-bromo-5-hydroxy-4-dimethylaminomethyl-1-methyl-2-phenylthiomethylindole-3- carboxylate. The compound according to the invention is an active principle of a pharmaceutical preparation having the antiviral, interferon-inducing and immunomodulatory effects.
