Improving properties of the nucleobase analogs T-705/T-1105 as potential antiviral.

4区 化学 Q3 Chemistry Annual Reports in Medicinal Chemistry Pub Date : 2021-01-01 DOI:10.1016/bs.armc.2021.08.002
Xiao Jia, Benedikt Ganter, Chris Meier
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引用次数: 4

Abstract

In this minireview we describe our work on the improvement of the nucleobase analogs Favipiravir (T-705) und its non-fluorinated derivative T-1105 as influenza and SARS-CoV-2 active compounds. Both nucleobases were converted into nucleotides and then included in our nucleotide prodrugs technologies cycloSal-monophosphates, DiPPro-nucleoside diphosphates and TriPPPro-nucleoside triphosphates. Particularly the DiPPro-derivatives of T-1105-RDP proved to be very active against influenza viruses. T-1105-derivatives in general were found to be more antivirally active as compared to their T-705 counterpart. This may be due to the low chemical stability of all ribosylated derivatives of T-705. The ribosyltriphosphate derivative of T-1105 was studied for the potential to act as a inhibitor of the SARS-CoV-2 RdRp and was found to be an extremely potent compound causing lethal mutagenesis. The pronucleotide technologies, the chemical synthesis, the biophysical properties and the biological effects of the compounds will be addressed as well.

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提高核碱基类似物T-705/T-1105作为潜在抗病毒药物的性能。
在这篇综述中,我们描述了我们在改进核碱基类似物Favipiravir (T-705)及其无氟衍生物T-1105作为流感和SARS-CoV-2活性化合物方面的工作。这两种核碱基都被转化为核苷酸,然后被纳入我们的核苷酸前药技术,即cyclosal - monophosp磷酸盐、dipppro -nucleoside diphosphate和TriPPPro-nucleoside triphosphate。特别是T-1105-RDP的dippro衍生物被证明对流感病毒具有很强的活性。总的来说,与T-705相比,t -1105衍生物的抗病毒活性更高。这可能是由于T-705的所有核基化衍生物的化学稳定性都很低。研究了T-1105的三磷酸核糖基衍生物作为SARS-CoV-2 RdRp抑制剂的潜力,发现它是一种非常有效的化合物,可引起致命的诱变。对化合物的原核苷酸技术、化学合成、生物物理性质和生物效应进行了综述。
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来源期刊
CiteScore
5.70
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0.00%
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0
审稿时长
>12 weeks
期刊介绍: Annual Reports in Medicinal Chemistry provides timely and critical reviews of important topics in medicinal chemistry with an emphasis on emerging topics in the biological sciences that are expected to provide the basis for entirely new future therapies.
期刊最新文献
The challenges and opportunities of developing small molecule inhibitors of MraY. Preface Anno 2021: Which antivirals for the coming decade? Improving properties of the nucleobase analogs T-705/T-1105 as potential antiviral. Broad spectrum antiviral nucleosides-Our best hope for the future.
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