175020-66-3

Upstream product

• 58479-61-1 tert-butylchlorodiphenylsilane 
• 34371-14-7 2-deoxy-D-ribonolactone 

Downstream Products

• 105930-84-5 tert-butyl(((2R,3S)-3-((tert-butyldiphenylsilyl)oxy)-2,3-dihydrofuran-2-yl)methoxy)diphenylsilane 
• 130277-32-6 ((2R,3S)-3-(tert-butyldiphenylsilyloxy)-2,3-dihydrofuran-2-yl)methanol 
• 940285-45-0 3,5-bis-O-(t-butyldiphenylsilyl)-2-deoxy-α-D-ribofuranosyl carbaldehyde 
• 940285-42-7 3,5-bis-O-(t-butyldiphenylsilyl)-2-deoxy-β-D-ribofuranosyl cyanide 
• 940285-41-6 3,5-bis-O-(t-butyldiphenylsilyl)-2-deoxy-α-D-ribofuranosyl cyanide 
• 940285-39-2 1-O-acetyl-3,5-bis-O-(t-butyldiphenylsilyl)-2-deoxy-D-ribofuranose 
• 940285-57-4 4-[2-(3,5-bis-O-(tert-butyldiphenylsilyl)-2-deoxy-α-D-ribofuranosyl)-E-vinyl]-5-methyl-thiazol-2-one 
• 940285-56-3 4-[2-(3,5-bis-O-(tert-butyldiphenylsilyl)-2-deoxy-α-D-ribofuranosyl)-Z-vinyl]-5-methyl-thiazol-2-one 
• 940285-55-2 4-[2-(3,5-bis-O-(tert-butyldiphenylsilyl)-2-deoxy-α-D-ribofuranosyl)-Z-vinyl]-N-(4-methoxybenzyl)-5-methyl-thiazol-2-one 

Relevant academic research and scientific papers

2′-Chloro,2′-fluoro Ribonucleotide Prodrugs with Potent Pan-genotypic Activity against Hepatitis C Virus Replication in Culture

Pan-genotypic nucleoside HCV inhibitors display a high genetic barrier to drug resistance and are the preferred direct-acting agents to achieve complete sustained virologic response in humans. Herein, we report, the discovery of a β-d-2′-Cl,2′-F-uridine phosphoramidate nucleotide 16, as a nontoxic pan-genotypic anti-HCV agent. Phosphoramidate 16 in its 5′-triphosphate form specifically inhibited HCV NS5B polymerase with no marked inhibition of human polymerases and cellular mitochondrial RNA polymerase. Studies on the intracellular half-life of phosphoramidate 16-TP in live cells demonstrated favorable half-life of 11.6 h, suggesting once-a-day dosing. Stability in human blood and favorable metabolism in human intestinal microsomes and liver microsomes make phosphoramidate 16 a prospective candidate for further studies to establish its potential value as a new anti-HCV agent.

Discovery of a Series of 2′-α-Fluoro,2′-β-bromo-ribonucleosides and Their Phosphoramidate Prodrugs as Potent Pan-Genotypic Inhibitors of Hepatitis C Virus

Hepatitis C virus (HCV) nucleoside inhibitors display pan-genotypic activity, a high barrier to the selection of resistant virus, and are some of the most potent direct-acting agents with durable sustained virologic response in humans. Herein, we report, the discovery of β-d-2′-Br,2′-F-uridine phosphoramidate diastereomers 27 and 28, as nontoxic pan-genotypic anti-HCV agents. Extensive profiling of these two phosphorous diastereomers was performed to select one for in-depth preclinical profiling. The 5′-triphosphate formed from these phosphoramidates selectively inhibited HCV NS5B polymerase with no inhibition of human polymerases and cellular mitochondrial RNA polymerase up to 100 μM. Both are nontoxic by a variety of measures and display good stability in human blood and favorable metabolism in human intestinal microsomes and liver microsomes. Ultimately, a preliminary oral pharmacokinetics study in male beagles showed that 28 is superior to 27 and is an attractive candidate for further studies to establish its potential value as a new clinical anti-HCV agent.

2' -DISUBSTITUTED NUCLEOSIDE ANALOGS FOR TREATMENT OF THE FLAVIVIRIDAE FAMILY OF VIRUSES AND CANCER

The present invention is directed to compounds, compositions and methods for treating or preventing Flaviviridae family of viruses (including HCV, Yellow fever, Dengue, Chikungunya and West Nile virus), RSV and influenza infection and cancer in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment or prevention of HCV infection.

Direct and facile syntheses of heterocyclic vinyl-C-nucleosides for recognition of inverted base pairs by DNA triple helix formation: First report by direct Wittig route

(Chemical Equation Presented) The ability to recognize specific gene sequences canonically would allow precise means for genetic intervention. However, specific recognition of two of the four possible base pairs by triplex-forming oligonucleotides (TFO) as X·T-A and Y·C-G within a triplex currently remains elusive. A series of C1-vinyl nucleosides have been proposed, and their stability and specificity have been evaluated extensively by molecular dynamics simulation. Because most C-nucleoside syntheses extend through direct substitution at the C1-position, a more convenient strategy for their syntheses via a direct Wittig coupling is presented here.