1246253-30-4

Upstream product

• 1246253-27-9 2'-deoxy-2'-fluoro-5'-O-TBDMS-cytidine 
• 10212-20-1 2'-deoxy-2'-fluorocytidine 
• 1246253-28-0 3'-O-N₄-bis(4-methoxytrityl)-5'-O-(t-butyldimethylsilyl)-2'-deoxy-2'-fluorocytidine 
• 1246253-29-1 3'-O-N₄-bis(4-methoxytrityl)-2'-deoxy-2'-fluorocytidine 

Downstream Products

• 1445379-41-8 C₅₀H₄₆FN₃O₇ 
• 1445381-83-8 C₃₇H₄₄FN₅O₆Si 
• 1445392-14-2 C₅₈H₆₂FN₅O₈Si 
• 1246253-31-5 3'-O,N₄-bis(4-methoxytrityl)-2'-deoxy-2'-fluoro-5'-C-methylcytidine 

Relevant academic research and scientific papers

Discovery of 4′-chloromethyl-2′-deoxy-3′,5′-di- O -isobutyryl-2′-fluorocytidine (ALS-8176), A first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is a leading pathogen of childhood and is associated with significant morbidity and mortality. To date, ribavirin is the only approved small molecule drug, which has limited use. The only other RSV drug is palivizumab, a monoclonal antibody, which is used for RSV prophylaxis. Clearly, there is an urgent need for small molecule RSV drugs. This article reports the design, synthesis, anti-RSV activity, metabolism, and pharmacokinetics of a series of 4′-substituted cytidine nucleosides. Among tested compounds 4′-chloromethyl-2′-deoxy-2′-fluorocytidine (2c) exhibited the most promising activity in the RSV replicon assay with an EC50 of 0.15 μM. The 5′-triphosphate of 2c (2c-TP) inhibited RSV polymerase with an IC50 of 0.02 μM without appreciable inhibition of human DNA and RNA polymerases at 100 μM. ALS-8176 (71), the 3′,5′-di-O-isobutyryl prodrug of 2c, demonstrated good oral bioavailability and a high level of 2c-TP in vivo. Compound 71 is a first-in-class nucleoside RSV polymerase inhibitor that demonstrated excellent anti-RSV efficacy and safety in a phase 2 clinical RSV challenge study.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.

SUBSTITUTED NUCLEOSIDE AND NUCLEOTIDE ANALOGS

Disclosed herein are nucleotide analogs with protected phosphates, methods of synthesizing nucleotide analogs with protected phosphates and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with the nucleotide analogs with protected phosphates.