Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents

Guo, Shuang; Xu, Meng; Guo, Qi; Zhu, Fuqiang; Jiang, Xiangrui; Xie, Yuanchao; Shen, Jingshan

doi:10.1016/j.bmc.2019.01.007

Cited by 6 publications

(9 citation statements)

References 26 publications

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“…Synthesis of several pyrazine nucleosides and their phosphoramidate prodrugs was described in ( Fig. 19 ) [ 80 ]. The activity of these nucleosides against the hepatitis C virus (HCV) was evaluated.…”

Section: Synthesis Of Favipiravir and Its Derivativesmentioning

confidence: 99%

“…The ethylamine group at position C3 of the heterocyclic ring caused a loss of the antiviral activity of compound ( 30d ) and its ( S )-phosphoramidate ( S-31d ). Compound ( 30e ) showed good activity with an EC 50 value of 7.3 µmol/L; however, attempts to convert it to a phosphoramidate prodrug failed [ 80 ].…”

Section: Synthesis Of Favipiravir and Its Derivativesmentioning

confidence: 99%

“…It was presumed that changing the position of the methyl group in the ribose moiety (compounds ( 33a–c )) may reduce their cytotoxicity. However, among these compounds, only the ( S )-isomer phosphoramidate prodrug ( S-34b ) was not cytotoxic at a concentration of 100 µmol/L, but it showed weak activity (EC 50 = 19.5 µM) [ 80 ].…”

Section: Synthesis Of Favipiravir and Its Derivativesmentioning

confidence: 99%

“…Ациклические нуклеотидные производные фавипиравира ОБЗОРЫ лучить на его основе фосфорамидатное пролекарство не удалось[80].Предполагалось, что изменение положения метильной группы в остатке рибозы (соединения (33ac)) позволит снизить их цитотоксичность. Однако среди этих соединений только (S)-изомерное фосфорамидатное пролекарство (S-34b) не было цитотоксичным при концентрации 100 мкмоль/л, но показало слабую активность (ЕС 50 = 19.5 мкМ)[80].Н а о с н о в е н е ф т ор и р о в а н н о г о о с н о в а н и я T-1105 синтезирован 3-оксо-4-(2'-C-метил-β-Dрибофуранозил)-2-пиразинкарбоксамид (рис. 21) в виде смеси αи β-аномеров.…”

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Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods

et al. 2022

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1,4-Pyrazine-3-carboxamide-based antiviral compounds have been under intensive study for the last 20 years. One of these compounds, favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, T-705), is approved for use against the influenza infection in a number of countries. Now, favipiravir is being actively used against COVID-19. This review describes the in vivo metabolism of favipiravir, the mechanism of its antiviral activity, clinical findings, toxic properties, and the chemical synthesis routes for its production. We provide data on the synthesis and antiviral activity of structural analogs of favipiravir, including nucleosides and nucleotides based on them.

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Section: Synthesis Of Favipiravir and Its Derivativesmentioning

confidence: 99%

Section: Synthesis Of Favipiravir and Its Derivativesmentioning

confidence: 99%

Section: Synthesis Of Favipiravir and Its Derivativesmentioning

confidence: 99%

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Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods

et al. 2022

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“…For example, in endocrine regulation, it acts as a regulator of androgen receptors to control the amount of hormone activity. , In the cell membrane, its role is also to activate sodium channel proteins to allow the smooth passage of sodium ions . Human main diseases are also increasing with the development of society, including neurodegenerative diseases, fibrotic diseases, and abnormal blood vessel leakage; C 4 H 3 BrN 2 O is also involved in the treatment of these diseases. , Not only that, it is not absent in the process of human anti-cancer, including treatment of many cancers such as liver cancer. , Because of its inhibitory effect on specific proteins, this has a great impact on the reproduction of viruses like human hepatitis C virus . It is precisely because of its many advantages mentioned above that further exploration and research on C 4 H 3 BrN 2 O are particularly important, and it also provides more references for the development of pyrazine derivatives in the future.…”

Section: Introductionmentioning

confidence: 99%

Solubility and Data Correlation of 2-Bromo-5-hydroxypyrazine in Four Cosolvent Mixtures and Ten Mono-Solvents from 278.15 to 323.15 K

2023

J. Chem. Eng. Data

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The experimental solubility of 2-bromo-5-hydroxypyrazine dissolved in 10 mono-solvents (methanol, ethanol, isopropanol, N,N-dimethylformamide (DMF), npropanol, acetonitrile, acetone, ethylene glycol (EG), propylene glycol (PG), water) and cosolvent mixtures of methanol + water, ethanol + water, isopropanol + water, and DMF + water was determined by the isothermal saturation method between 278.15 and 323.15 K at 101.2 kPa. The largest solubility was observed in DMF + 2-bromo-5hydroxypyrazine for mono-solvent systems and in DMF + water for mixed solvent systems. The Jouyban−Acree model (J−A), van't Hoff−Jouyban−Acree model (V−J− A), and Apelblat−Jouyban−Acree model (A−J−A) were utilized to correlate the 2bromo-5-hydroxypyrazine solubility in mixtures, and the Apelblat model, van't Hoff model, λh model, and Jouyban model were used to correlate the 2-bromo-5hydroxypyrazine solubility in 10 mono-solvents. The preferential solvation of 2bromo-5-hydroxypyrazine in mixed solvents was researched by calculation of δx 1,3 . This study presents insights into modulating the 2-bromo-5-hydroxypyrazine crystallization process and in understanding equilibrium behaviors in different solvents.

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Pharmacological Potential of Pyrmidine Derivatives: A Review With Emphasis on Antiviral Effects and Virtual Screening Against Sars‐Cov‐2 Molecular Targets

et al. 2023

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The importance of R&D of new antivirals has been highly evident with the emergence of the pandemic caused by SARS‐CoV‐2. Pyrimidines are heterocyclic compounds with a broad biological spectrum. In this review we emphasize the antiviral application of pyrimidines. Scientific articles, drug and patent registrations were searched using terms involving antiviral pyrimidines. Between 2012 and 2022, more than 100 articles, which show the broad antiviral spectrum of these compounds, were added in this review. The publications of the last five years were prioritized. Anti‐HIV applications were found, their use more evident within the framework of antivirals; among others found were anti‐influenza, anti‐arboviral, and anti‐hepatitis viruses. The results found in the drug and patent databases corroborate the scenario observed in the analysis of scientific articles and demonstrate the importance of researching pyrimidine compounds in periods of great impact on global health. Additionally, through virtual screening of 119 pyrimidines from an in‐house library, we found seventeen pyrimidines with high binding potential with the Mpro and RdRp proteins of SARS‐CoV‐2. Almost all seventeen compounds showed good pharmacokinetic and toxicological profile, mainly compounds 150 and 151 being considered promising for biological evaluation against SARS‐CoV‐2.

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Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents

Cited by 6 publications

References 26 publications

Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods

Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods

Solubility and Data Correlation of 2-Bromo-5-hydroxypyrazine in Four Cosolvent Mixtures and Ten Mono-Solvents from 278.15 to 323.15 K

Pharmacological Potential of Pyrmidine Derivatives: A Review With Emphasis on Antiviral Effects and Virtual Screening Against Sars‐Cov‐2 Molecular Targets

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