Design, synthesis, and biological evaluation of novel 2′-deoxy-2′-fluoro-2′-C-methyl 8-azanebularine derivatives as potent anti-HBV agents

Yang, Wenzhong; Peng, Youmei; Wang, Jingwen; Song, Chuanjun; Yu, Wenquan; Zhou, Yubing; Jiang, Jinhua; Wang, Qingduan; Wu, Jie; Chang, Junbiao

doi:10.1016/j.bmcl.2019.04.005

Cited by 6 publications

(2 citation statements)

References 35 publications

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“…To build a pyrimidine ring based on 5-amino-4-triazolocarboxylic acid amides 83 and to form 3,6-disubstituted triazolo [4,5-d] orthoesters [8,34,47,48], amides and formic acid esters were used as one-carbon reagents [41, 49 -51], as well as Vilsmeier-Haack reagent [50] (Scheme 25).…”

Section: The Cyclization Of 5-amino-123-triazole-4-carboxamidesmentioning

confidence: 99%

1,2,3-Triazole-4(5)-amines – Convenient Synthetic Blocks for the Construction of Triazolo-Annulated Heterocycles

СИРОТА

Kemskiy

Saliyeva

et al. 2022

J. Org. Pharm. Chem.

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Aim. To analyze and summarize the synthetic potential of 1,2,3-triazole-4(5)-amines as efficient building blocks in the synthesis of triazolo-annulated pyridine, azine and azepine systems.Results and discussion. Original literature sources revealing the synthetic potential of 4(5)-amino functionalized 1,2,3-triazoles as convenient and available building blocks for the preparation of triazolo-annulated pyridines, azines and azepines were analyzed and systematized. Condensation of 1,2,3-triazole-4(5)-amines with methylene active compounds was shown to be a powerful tool for the synthesis of versatile triazolo[4,5-b]pyridines. In turn, the cyclocondensation based on 5-amino-1,2,3-triazole-4-carboxylic acids and their structurally modified derivatives was proven to be a general way for obtaining a number of triazolo[4,5-d]pyrimidine systems. Few representatives of triazolo-annulated pyridazines, 1,3-oxazines and 1,3-thiazines were synthesized by the intramolecular cyclization of the corresponding 4-aryl(carboxy-, aminomethyl)-5-amino-1,2,3-triazoles. The cyclocondensation involving 4,5-diamino-, 4-carbofunctionalized 5-amino-1,2,3-triazoles and 4-amino-5-thiocarboxamido-1,2,3-triazoles was successful for the construction of di-, oxa- and thiazepino-annulated triazoles.Conclusions. The analysis, systematization and summary of the literature regarding the synthetic potential of 1,2,3-triazole-4(5)-amines conclusively demonstrate that these structures are easily available and convenient molecular blocks for the construction of triazolo-annulated pyridine, azine and azepine systems that are important for synthetic and biomedical research.

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Section: The Cyclization Of 5-amino-123-triazole-4-carboxamidesmentioning

confidence: 99%

1,2,3-Triazole-4(5)-amines – Convenient Synthetic Blocks for the Construction of Triazolo-Annulated Heterocycles

СИРОТА

Kemskiy

Saliyeva

et al. 2022

J. Org. Pharm. Chem.

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“…HBV therapy with nucleoside analogs, in long term, has developed resistance and obvious decreased inhibition effects [ 8 , 9 , 10 ]. The disadvantages of nucleoside analogs prompted us and other researchers to invent and find new structural non-nucleoside analog compounds [ 11 , 12 , 13 , 14 , 15 , 16 ]. Many anti-HBV bioactive non-nucleoside analog compounds have been designed and developed on the basis of their interactions with receptor using molecular docking [ 17 , 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents

et al. 2020

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Oxime derivatives of dehydrocholic acid and its esters were designed for anti-hepatitis B virus (HBV) drugs according to principles of assembling active chemical fragments. Twelve compounds were synthesized from dehydrocholic acid by esterification and oxime formation, and their anti-hepatitis B virus (HBV) activities were evaluated with HepG 2.2.15 cells. Results showed that 5 compounds exhibited more effective inhibition of HBeAg than positive control, among them 2b-3 and 2b-1 showed significant anti-HBV activities on inhibiting secretion of HBeAg (IC50 (2b-3) = 49.39 ± 12.78 μM, SI (2b-3) = 11.03; IC50 (2b-1) = 96.64 ± 28.99 μM, SI (2b-1) = 10.35) compared to the Entecavir (IC50 = 161.24 μM, SI = 3.72). Molecular docking studies showed that most of these compounds interacted with protein residues of heparan sulfate proteoglycan (HSPG) in host hepatocyte and bile acid receptor.

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Design of novel broad‐spectrum antiviral nucleoside analogues using natural bases ring‐opening strategy

Du,

Yang,

Zhao

et al. 2024

Drug Development Research

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The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA‐dependent RNA polymerase (RdRp) has emerged as a potential target for broad‐spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently‐used structural substitution methods to design new nucleoside analogues is challenging. In this study, we explore the use of the “ring‐opening” strategy to design new base mimics, thereby using these base mimics to design new nucleoside analogues with broad‐spectrum antiviral activities. A total of 29 compounds were synthesized. Their activity against viral RdRp was initially screened using an influenza A virus RdRp high‐throughput screening model. Then, the antiviral activity of 38a was verified against influenza virus strain A/PR/8/34 (H1N1), demonstrating a 50% inhibitory concentration (IC50) value of 9.95 μM, which was superior to that of ribavirin (the positive control, IC50 = 11.43 μM). Moreover, 38a also has inhibitory activity against coronavirus 229E with an IC50 of 30.82 μM. In addition, compounds 42 and 46f exhibit an 82% inhibition rate against vesicular stomatitis virus at a concentration of 20 μM and hardly induce cytotoxicity in host cells. This work demonstrates the feasibility of designing nucleoside analogues with “ring‐opening” bases and suggests the “ring‐opening” nucleosides may have greater polarity, and designing prodrugs is an important aspect of optimizing their antiviral activity. Future research should focus on enhancing the conformational restriction of open‐loop bases to mimic Watson‐Crick base pairing better and improve antiviral activity.

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Design, synthesis, and biological evaluation of novel 2′-deoxy-2′-fluoro-2′-C-methyl 8-azanebularine derivatives as potent anti-HBV agents

Cited by 6 publications

References 35 publications

1,2,3-Triazole-4(5)-amines – Convenient Synthetic Blocks for the Construction of Triazolo-Annulated Heterocycles

1,2,3-Triazole-4(5)-amines – Convenient Synthetic Blocks for the Construction of Triazolo-Annulated Heterocycles

Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents

Design of novel broad‐spectrum antiviral nucleoside analogues using natural bases ring‐opening strategy

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