- Method for synthesizing arbidol hydrochloride intermediate
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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.
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Paragraph 0015
(2020/08/25)
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- ARBIDOL ANALOGS WITH IMPROVED INFLUENZA HEMAGGLUTININ POTENCY
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The invention provides a series of analogs of arbidol having enhanced binding activity with respect to influenza hemagglutinin. Accordingly, the invention can provide a method of inhibiting the bioactivity of viral hemagglutinin activity, which is an essential step in the entry of infectious viral particles into host cells. The invention also can provide a method of treatment of influence, comprising administering an effective amount of a compound of formula (A), wherein X is S or O, to a patient afflicted therewith.
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Page/Page column 9-10; 12
(2018/07/05)
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- Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin
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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.
- Wright, Zo? V.F.,Wu, Nicholas C.,Kadam, Rameshwar U.,Wilson, Ian A.,Wolan, Dennis W.
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supporting information
p. 3744 - 3748
(2017/07/27)
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- Indole derivative having antiviral, interferon-inducing and immunomodulatory effects
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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.
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