Synthesis of a new antiviral agent, arbidole

Trofimov, F. A.; Tsyshkova, N. G.; Zotova, S. A.; Grinev, A. N.

doi:10.1007/bf00772858

Cited by 23 publications

(12 citation statements)

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“…One of the first descriptions of its chemical synthesis was published in 1993 (Trofimov et al, 1993), and modified later on Miller and Bergeron (1994). The drug is manufactured by Moscow-based Masterlek™, a subsidiary of Pharmstandard Group (see below), and by Shijiazhuang No.4 Pharmaceutical™ in China (http://www.sjzsiyao.com/products_detail/&productId=46.html).…”

Section: Introductionmentioning

confidence: 99%

Arbidol as a broad-spectrum antiviral: An update

2014

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Arbidol (ARB) is a Russian-made small indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It also demonstrates inhibitory activity against other viruses, enveloped or not, responsible for emerging or globally prevalent infectious diseases such as hepatitis B and C, gastroenteritis, hemorrhagic fevers or encephalitis. In this review, we will explore the possibility and pertinence of ARB as a broad-spectrum antiviral, after a careful examination of its physico-chemical properties, pharmacokinetics, toxicity, and molecular mechanisms of action. Recent studies suggest that ARB's dual interactions with membranes and aromatic amino acids in proteins may be central to its broad-spectrum antiviral activity. This could impact on the virus itself, and/or on cellular functions or critical steps in virus-cell interactions, thereby positioning ARB as both a direct-acting antiviral (DAA) and a host-targeting agent (HTA). In the context of recent studies in animals and humans, we will discuss the prospective clinical use of ARB in various viral infections.

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Section: Introductionmentioning

confidence: 99%

Arbidol as a broad-spectrum antiviral: An update

2014

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“…The first synthetic approach to obtain Arbidol was reported in 1993 by Trofimov, involving decoration of the aromatic ring of the indole derivatives 30 previously synthesized by the same group ( Scheme 19 ) [ 63 ].…”

Section: Arbidolmentioning

confidence: 99%

Metal-Promoted Heterocyclization: A Heterosynthetic Approach to Face a Pandemic Crisis

2021

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The outbreak of SARS-CoV-2 has drastically changed our everyday life and the life of scientists from all over the world. In the last year, the scientific community has faced this worldwide threat using any tool available in order to find an effective response. The recent formulation, production, and ongoing administration of vaccines represent a starting point in the battle against SARS-CoV-2, but they cannot be the only aid available. In this regard, the use of drugs capable to mitigate and fight the virus is a crucial aspect of the pharmacological strategy. Among the plethora of approved drugs, a consistent element is a heterocyclic framework inside its skeleton. Heterocycles have played a pivotal role for decades in the pharmaceutical industry due to their high bioactivity derived from anticancer, antiviral, and anti-inflammatory capabilities. In this context, the development of new performing and sustainable synthetic strategies to obtain heterocyclic molecules has become a key focus of scientists. In this review, we present the recent trends in metal-promoted heterocyclization, and we focus our attention on the construction of heterocycles associated with the skeleton of drugs targeting SARS-CoV-2 coronavirus.

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“…Arbidol was prepared as described in [5]. Hydrochlorides of substituted ethyl esters of 6-bromo-2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids (4a -g), general preparation method.…”

Section: Experimental Chemical Sectionmentioning

confidence: 99%

“…Substituted ethyl esters of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids 4 -7 were prepared (scheme 1) from 1-substituted ethyl esters of 5-hydroxy-2-methyl-1H-indole-3-carboxylic acids 1a -e, which, by analogy [5] with 1,2-dimethylindole (compound 1a), were sequentially converted to 5-acetyloxy-(compounds 2a -e) and 5-acetyloxy-6-bromoindoles (compounds 3a -e). Interaction of these latter compounds with dimethylamine, pyrrolidine, and morpholine gave the corresponding 2-aminomethyl-6-bromoindoles (4a -g).…”

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confidence: 99%

Synthesis and Antiviral Activity of Substituted Ethyl-2-Aminomethyl-5-Hydroxy-1H-Indole-3-Carboxylic Acids and Their Derivatives

et al. 2015

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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.Keywords: 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids, antiviral activity, antiinfluenza activity, influenza A/Aichi/2/69 (H3N2), BVDV, HCV.Substituted 2-and 4-aminomethyl-5-hydroxyl-1H-indole-3-carboxylic acids are known to have some degree of antiviral activity [1 -3]. In particular, 1-benzyl-2-dimethylaminomethyl-3-carbethoxy-5-acetoxy-6-bromoindole hydrochloride demonstrated antiinfluenza activity in studies using a mouse model of influenza pneumonia [3]. We have previously described the synthesis and antiviral activity of a series of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids and have shown them to have limited activity against influenza A/New Caledonia/20/99 (H1N1) virus, bovine viral diarrhea virus (BVDV), and HCV [4].We describe here the synthesis and antiviral activities of novel derivatives of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids (compounds 4 -7, 11, 16 -20, 24). Substituted ethyl esters of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids 4 -7 were prepared (scheme 1) from 1-substituted ethyl esters of 5-hydroxy-2-methyl-1H-indole-3-carboxylic acids 1a -e, which, by analogy [5] with 1,2-dimethylindole (compound 1a), were sequentially converted to 5-acetyloxy-(compounds 2a -e) and 5-acetyloxy-6-bromoindoles (compounds 3a -e). Interaction of these latter compounds with dimethylamine, pyrrolidine, and morpholine gave the corresponding 2-aminomethyl-6-bromoindoles (4a -g). 6-Bromoindoles 4b,c were hydrogenated with hydrogen on 10% Pd/C to form indoles unsubstituted at position 6 (compounds 5a, b); reaction of 6-bromoindole 4a with copper (I) cyanide in N-methylpyrrolidone (NMP) produced the corresponding 6-cyanoindole compound 6, while use of

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Synthesis of a new antiviral agent, arbidole

Cited by 23 publications

References 0 publications

Arbidol as a broad-spectrum antiviral: An update

Arbidol as a broad-spectrum antiviral: An update

Metal-Promoted Heterocyclization: A Heterosynthetic Approach to Face a Pandemic Crisis

Synthesis and Antiviral Activity of Substituted Ethyl-2-Aminomethyl-5-Hydroxy-1H-Indole-3-Carboxylic Acids and Their Derivatives

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