2164516-85-0

Upstream product

• 863329-66-2 2'-deoxy-2'-fluoro-2'-methyluridine 
• 245078-14-2 (2S)-ethyl 2-(chloro(phenoxy)phosphorylamino)propanoate 
• 168427-35-8 (3R,4S,5R)-4-((2,4-dichlorobenzyl)oxy)-5-(((2,4-dichlorobenzyl)oxy)methyl)-2-methoxytetrahydrofuran-3-ol 
• 443642-30-6 3,5-bis-O-(2,4-dichlorophenylmethyl)-1-O-methyl-α-D-erythro-pentafuranos-2-ulose 
• 443642-31-7 (2S,3R,4R,5R)-4-((2,4-dichlorobenzyl)oxy)-5-(((2,4-dichlorobenzyl)oxy)methyl)-2-methoxy-3-methyltetrahydrofuran-3-ol 
• 677299-16-0 (2R,3R,4R)-3,4-bis((2,4-dichlorobenzyl)oxy)-2-(((2,4-dichlorobenzyl)oxy)methyl)-5-methoxytetrahydrofuran 
• 1403250-94-1 (2S)-2-(((perfluorophenoxy)(phenoxy)phosphoryl)amino)propionic acid ethyl ester 
• 2041584-99-8 1-((2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione 
• 1315584-52-1 C₂₉H₃₃FN₃O₁₁P 
• 1256490-58-0 benzyl (2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1-(2H)-yl)-4-fluoro-2-(hydroxymethyl)-4-methyl-tetrahydrofuran-3-yl carbonate 
• 1315584-51-0 benzyl (2R,3R,4R,5R)-2-((tert-butyldimethylsilyloxy)methyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1-(2H)-yl)-4-fluoro-4-methyltetrahydrofuran-3-yl carbonate 
• 1160557-97-0 1-((2R,3R,4R,5R)-5-((tert-butyldimethylsilyloxy)methyl)-3-fluoro-4-hydroxy-3-methyl-tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione 

Relevant academic research and scientific papers

Discovery of 2'-α-C-Methyl-2'-β-C-fluorouridine Phosphoramidate Prodrugs as Inhibitors of Hepatitis C Virus

2′-α-C-Methyl-2′-β-C-fluorouridine and its phosphoramidate prodrugs were synthesized and evaluated for their inhibitory activity against HCV. The structure?activity relationship analysis of the phosphoramidate moiety found that 17m, 17q, and 17r exhibit potent activities against HCV, with EC50 values of 1.82 ± 0.19, 0.88 ± 0.12, and 2.24 ± 0.22 μM, respectively. The docking study revealed that the recognition of the 2′-β-F by Arg158, 3′-OH by N291, and the Watson?Crick pairing with the template allowed 23 to form the in-line conformation necessary for its incorporation into the viral RNA chain.

Efficient synthesis of nucleoside aryloxy phosphoramidate prodrugs utilizing benzyloxycarbonyl protection

An efficient method for the synthesis of nucleoside phosphoramidates prodrugs (6a-f) has been developed that employs a simple protection/deprotection sequence of the nucleoside with benzyloxycarbonyl (Cbz). The coupling reaction of Cbz-protected derivativ

NUCLEOSIDE PHOSPHORAMIDATE PRODRUGS

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Discovery of a luoro-2′-β- C -methyluridine Nucleotide Prodrug (PSI-7977) for the treatment of hepatitis C virus

Hepatitis C virus (HCV) is a global health problem requiring novel approaches for effective treatment of this disease. The HCV NS5B polymerase has been demonstrated to be a viable target for the development of HCV therapies. β-d-2′-Deoxy-2′-α-fluoro-2′-β-C-methyl nucleosides are selective inhibitors of the HCV NS5B polymerase and have demonstrated potent activity in the clinic. Phosphoramidate prodrugs of the 5′-phosphate derivative of the β-d-2′-deoxy-2′-α- fluoro-2′-β-C-methyluridine nucleoside were prepared and showed significant potency in the HCV subgenomic replicon assay (1 μM) and produced high levels of triphosphate 6 in primary hepatocytes and in the livers of rats, dogs, and monkeys when administered in vivo. The single diastereomer 51 of diastereomeric mixture 14 was crystallized, and an X-ray structure was determined establishing the phosphoramidate stereochemistry as Sp, thus correlating for the first time the stereochemistry of a phosphoramidate prodrug with biological activity. 51 (PSI-7977) was selected as a clinical development candidate.