1255860-40-2

Upstream product

• 39825-33-7 isopropyl L-alanine 
• 1255860-30-0 1-((2R,3R,4R,5R)-3-allyl-4-(benzyloxy)-5-(benzyloxymethyl)-3-hydroxytetra-hydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione 
• 1255860-31-1 1-[(2R,3R,4R,5R)-4-(benzyloxy)-5-(benzyloxy-methyl)-3-hydroxy-3-(2-hydroxyethyl)tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione 
• 1532523-61-7 C₂₆H₃₀N₂O₉S 
• 885592-69-8 (2S,4R,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-2-methoxydihydrofuran-3(2H)-one 
• 1378911-66-0 1-((6aR,8R,9R,9aR)-2,2,4,4-tetraisopropyldihydro-6H,8H-spiro[furo[3,2-f ][1,3,5,2,4]trioxadisilocine-9,2′-oxetan]-8-yl)pyrimidine-2,4(1H,3H)-dione 
• 1610050-20-8 C₂₃H₄₁N₃O₆Si₂ 
• 1256490-52-4 (S)-2-[(2,3,4,5,6-pentafluorophenoxy)phenoxyphosphorylamino]propionic acid isopropyl ester 
• 1378911-73-9 4-amino-1-((4R,5R,7R,8R)-8-hydroxy-7-(hydroxymethyl)-1,6-dioxaspiro[3.4]octan-5-yl)pyrimidin-2(1H)-one 
• 1255860-29-7 (2S,3R,4R,5R)-3-allyl-4-(benzyloxy)-5-(benzyl-oxymethyl)-2-methoxytetrahydrofuran-3-yl benzoate 
• 770-12-7 O-phenyl phosphorodichloridate 
• 261909-49-3 phenyl(isopropoxy-L-alaninyl) phosphorochloridate 
• 1255860-33-3 1-[(4R,5R,7R,8R)-8-hydroxy-7-(hydroxyl-methyl)-1,6-dioxaspiro[3.4]octan-5-yl]pyrimidine-2,4(1H,3H)-dione 
• 1255860-32-2 1-[(4R,5R,7R,8R)-8-(benzyloxy)-7-(benzyloxy-methyl)-1,6-dioxaspiro[3.4]octan-5-yl]pyrimidine-2,4(1H,3H)-dione 

Relevant academic research and scientific papers

Nucleotide prodrugs of 2′-deoxy-2′-spirooxetane ribonucleosides as novel inhibitors of the HCV NS5B polymerase

The limited efficacy, in particular against the genotype 1 virus, as well as the variety of side effects associated with the current therapy for hepatitis C virus (HCV) infection necessitates more efficacious drugs. We found that phosphoramidate prodrugs of 2′-deoxy-2′-spirooxetane ribonucleosides form a novel class of HCV NS5B RNA-dependent RNA polymerase inhibitors, displaying EC50 values ranging from 0.2 to >98 μM, measured in the Huh7-replicon cell line, with no apparent cytotoxicity (CC50 > 98.4 μM). Confirming recent findings, the 2′-spirooxetane moiety was identified as a novel structural motif in the field of anti-HCV nucleosides. A convenient synthesis was developed that enabled the synthesis of a broad set of nucleotide prodrugs with varying substitution patterns. Extensive formation of the triphosphate metabolite was observed in both rat and human hepatocyte cultures. In addition, after oral dosing of several phosphoramidate derivatives of compound 21 to rats, substantial hepatic levels of the active triphosphate metabolite were found.

Use of 2′-spirocyclic ethers in HCV nucleoside design

Conformationally restricted 2′-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2′-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS5B polymerase, with IC50 = 8.48 μM. Activity against NS5B bearing the S282T mutation was reduced. Phosphoramidate prodrugs of a 2′-oxetane 2-amino-6-O-methyl-purine nucleoside demonstrated potent anti-HCV activity in vitro, and the corresponding triphosphate retained similar potent activity against both wild-type and S282T HCV NS5B polymerase.

URACYL SPIROOXETANE NUCLEOSIDES

Compounds of the formula (I) including any possible stereoisomers thereof, wherein: R4 is a monophosphate, diphosphate or triphosphate ester; or R4 is formula (II) or formula (III), R7 is optionally substituted phenyl, opt