40945-79-7Relevant articles and documents
An Urgent Industrial Scheme Both for Total Synthesis, and for Pharmaceutical Analytical Analysis of Umifenovir as an Anti-viral API for Treatment of COVID-19
Beheshti, Abolghasem,Dadras, Akbar,Naeimi, Sedigheh Sadat,Rezvanfar, Mohammad Amin,Siadati, Seyyed Amir
, p. 838 - 846 (2022/03/02)
Background: This paper aims to reveal an urgent industrial scheme for a fast and facile total synthesis of umifenovir (arbidol) (by one-pot stages) as an antiviral agent for treating the 2019-nCoV virus via inhibiting its viral replication in the human cells. As COVID-19 takes thousands of lives all around the world, it seems that the medicinal resources would not be enough to supply billions of peoples currently living on the planet. Thus, this pandemic and its subsequent impacts on the natural order of our life would be one of the most important threats against the entire human race. Methods: In this project, we have made attempts to find an operative approach for synthesizing this compound as an active pharmaceutical ingredient (API), which showed it could be effective in inhibiting the newly emerged coronavirus. Results: The designed scheme uses relatively cheap precursors and contains one pot stage instead of seven time-consuming and more costly linear steps. Moreover, safe and cheap solvents have been used like water and ethanol, instead of toxic ones like methanol and pyridine which could cause rejection of the API in the organic volatile impurities (OVI) test of pharmacopeia analysis, as well as increase the concern of inflammability, explosivity, and carcinogenic properties of those common solvents. Conclusion: The most important pharmaceutical analytical methods containing OVI test (mainly ethanol (about 171 ppm) much lower than the limits, by gas chromatography-Flame Ionization Detector (GC-FID) instrument), assay content (about 99.6% by potentiometric titration), and related purity analysis (by high-performance liquid chromatography-Ultraviolet Detector (HPLC-UV)) (about 99.8%) were performed and described to give a more clear industrial scheme.
Preparation method of arbidol intermediate
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, (2020/07/02)
The invention discloses a preparation method of an arbidol intermediate. Ethyl acetoacetate, monomethylamine and p-benzoquinone used as initial raw materials undergo methylation, cyclization, acetylation, bromination and benzene vulcanization to prepare the target compound ethyl 5-hydroxy-6-bromo-2-phenylthiomethyl-1-methylindole-3-carboxylate. The preparation method of the arbidol intermediate issimple and convenient to operate, cheap and easily available in raw materials, high in yield, low in cost, good in quality, environment-friendly, mild in reaction condition, high in safety productioncoefficient and suitable for large-scale industrial production.
Method for synthesizing arbidol hydrochloride intermediate
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Paragraph 0012, (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.
Synthesis, single crystal X-ray analysis, and vibrational spectral studies of ethyl 6-bromo-5-((5-bromopyrimidin-2-yl)oxy)-2-((2, 6-dimethylmorpholino)methyl)-1-methyl-1H-indole-3-carboxylate
Luo, Dali,Ma, Lanlan,Zhou,Huang, Zhuyan
, (2019/08/12)
A new mecarbinate derivative, ethyl 6-bromo-5-((5-bromopyrimidin-2-yl)oxy)-2-((2,6- dimethylmorpholino)methyl)-1-methyl-1H-indole-3-carboxylate (1), was synthesized, and single crystals were grown by the gradual evaporation of acetone under ambient conditions. The optimized molecular crystal structure was determined based on DFT calculations at the B3LYP/6311G (2 d, p) level. Experimental and theoretical studies on the structure of the titled compound are presented.
ARBIDOL ANALOGS WITH IMPROVED INFLUENZA HEMAGGLUTININ POTENCY
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Page/Page column 9-11, (2018/07/05)
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.
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.
5 - Hydroxy indoles containing heterocyclic ring derivative and its use
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Paragraph 0199; 0200, (2018/05/03)
The present invention relates to a heterocyclic ring-containing 5-hydroxy indole derivative as represented by formula I, comprising a racemate of the derivative, an optical isomer of same, and a pharmaceutically acceptable salt and/or hydrate thereof, where substituent R1, R2, X, Y, and Z have the meanings as provided in the description. The compound of formula I is applicable in preparing a medicament for treatment and/or prevention of viral infections, and particularly for preparing an anti-hepatitis B virus medicament and anti-influenza virus medicament.
Preparation method of arbidol hydrochloride
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, (2017/02/09)
The invention discloses a preparation method of arbidol hydrochloride. P-nitrophenol which is cheap and easy to obtain is innovatively adopted as the raw material, and through acetylation, nitroreduction, an indole ring reaction, a methylation reaction, bromination, a reaction with thiophenol and deprotection, a Mannich reaction and salification, arbidol hydrochloride is obtained. Reaction conditions of the whole synthesis process are mild, the raw material can be conveniently obtained, the character of the product is good, the yield is high, few by-products are generated, reaction selectivity and purity are high, environmental friendliness is achieved, production cost is low, and the method is suitable for industrial production; the defects that in the prior art, selectivity is low, many by-products are generated, the yield is low, precious catalysts are used, and serious environmental pollution is caused are overcome.
Synthesis and Antiviral Activity of Substituted Ethyl-2-Aminomethyl-5-Hydroxy-1H-Indole-3-Carboxylic Acids and Their Derivatives
Ivachtchenko,Yamanushkin,Mitkin,Kisil,Korzinov,Vedenskii, V. Yu.,Leneva,Bulanova,Bichko,Okun,Ivashchenko,Ivanenkov, Ya. A.
, p. 151 - 162 (2016/02/14)
Novel substituted 5-hydroxy-2-aminomethyl-1H-indole-3-carboxylic acids and their derivatives were synthesized. The antiviral properties of these compounds were investigated in relation to bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV), and influenza A/Aichi/2/69 (H3N2) virus. Of the compounds synthesized here, only the 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-pyridin-3-yl- and 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-fluoro-1H-indole-3-carboxylic acid ethyl ester hydrochlorides had significant activity against these viruses, these agents not only suppressing the replication of influenza A/Aichi/2/69 (H3N2) virus in cell cultures at micromolar concentrations, but also demonstrating high efficacy, greater than that of Arbidol, in a model of influenza pneumonia in mice infected with influenza A/Aichi/2/69 (H3N2) virus, when given at a dose of 25 mg/kg/day.
Further studies on ethyl 5-hydroxy-indole-3-carboxylate scaffold: Design, synthesis and evaluation of 2-phenylthiomethyl-indole derivatives as efficient inhibitors of human 5-lipoxygenase
Peduto, Antonella,Bruno, Ferdinando,Dehm, Friedrike,Krauth, Verena,De Caprariis, Paolo,Weinigel, Christina,Barz, Dagmar,Massa, Antonio,De Rosa, Mario,Werz, Oliver,Filosa, Rosanna
, p. 492 - 498 (2014/06/10)
5-Lipoxygenase (5-LO), an enzyme that catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes, is an attractive drug target for the pharmacotherapy of inflammatory and allergic diseases. Here, we present the design, synthesis and
