{"title":"Improving properties of the nucleobase analogs T-705/T-1105 as potential antiviral.","authors":"Xiao Jia, Benedikt Ganter, Chris Meier","doi":"10.1016/bs.armc.2021.08.002","DOIUrl":null,"url":null,"abstract":"<p><p>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, Di<i>PP</i>ro-nucleoside diphosphates and Tri<i>PPP</i>ro-nucleoside triphosphates. Particularly the Di<i>PP</i>ro-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.</p>","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"57 ","pages":"1-47"},"PeriodicalIF":0.0000,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553380/pdf/","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual Reports in Medicinal Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/bs.armc.2021.08.002","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Chemistry","Score":null,"Total":0}
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.
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.