1191237-49-6

Basic information

• Product Name: 1′-cyano-2′-C-methyl-4-aza-7,9-dideazaadenosine
• Synonyms: 1′-cyano-2′-C-methyl-4-aza-7,9-dideazaadenosine
• CAS NO: 1191237-49-6
• Molecular Weight: 305.293
• Mol File: 1191237-49-6.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: 1′-cyano-2′-C-methyl-4-aza-7,9-dideazaadenosine(CAS DataBase Reference)
• NIST Chemistry Reference: 1′-cyano-2′-C-methyl-4-aza-7,9-dideazaadenosine(1191237-49-6)
• EPA Substance Registry System: 1′-cyano-2′-C-methyl-4-aza-7,9-dideazaadenosine(1191237-49-6)

Safety Data

• Hazardous Substances Data: 1191237-49-6(Hazardous Substances Data)

Usage

Chemical structure

A modified form of adenosine, a natural nucleoside found in all living cells.

Potency

Potent inhibitor of adenylyl cyclase.

Applications

Potential use in the treatment of certain cancers and inflammatory diseases.

Synthesis

Synthesized through a series of chemical reactions involving the introduction of a cyano group at the 1′ position, a C-methyl group at the 2′ position of the ribose ring, and the replacement of the 7 and 9 nitrogen atoms with carbon atoms.

Biological activity

Modification alters the biological activity of the molecule, making it a promising candidate for further research and drug development.

Upstream product

• 1191237-41-8 C₂₈H₃₂O₅ 
• 1191237-40-7 C₇H₁₄O₅ 
• 1314972-33-2 (3R,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)-3-methyl-tetrahydro-furan-2-ol 
• 1272971-35-3 2′,3′,5′-O-tribenzyl-1′-cyano-2′-C-methyl-4-aza-7,9-dideazaadenosine 
• 917567-08-9 (3R,4R,5R)-3,4-bis(benzyloxy)-5-[(benzyloxy)methyl]-3-methyloxolan-2-one 
• 937046-98-5 7-bromo-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine 
• 1191237-48-5 C₃₄H₃₃N₅O₄ 

Downstream Products

• 1350735-57-7 (2S)-isopropyl 2-((((2R,3R,4R,5R)-5-(4-aminopyrrolo[1,2-f]-[1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate 
• 1350735-68-0 (2S)-isopropyl 2-((((2R,3R,4R,5R)-3-isobutyroxy-5-(4-aminopyrrolo[1,2-f][1,2,4]triazin-7-yl)-5-cyano-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate 
• 1350735-69-1 C₂₉H₃₇N₆O₉P 
• 1350735-70-4 [(Sp)-isopropyl 2-((S)-(((2R,3R,4R,5R)-3-isobutyroxy-5-(4-aminopyrrolo[1,2-f][1,2,4]triazin-7-yl)-5-cyano-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy) (phenoxy)phosphorylamino)propanoate] 
• 1384122-46-6 C₂₅H₃₁N₆O₈P 
• 1431932-97-6 (2S)-isopropyl 2-((((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[1,2-f][1,2,4]triazin-7-yl)-6-cyano-6a-methyl-2-oxotetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methoxy)(phenoxy)phosphorylamino)propanoate 
• 1354823-59-8 (Sp)-isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(4-aminopyrrolo[1,2-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate 

Relevant articles and documents

Discovery of the first C -nucleoside HCV polymerase inhibitor (GS-6620) with demonstrated antiviral response in HCV infected patients

Hepatitis C virus (HCV) infection presents an unmet medical need requiring more effective treatment options. Nucleoside inhibitors (NI) of HCV polymerase (NS5B) have demonstrated pan-genotypic activity and durable antiviral response in the clinic, and they are likely to become a key component of future treatment regimens. NI candidates that have entered clinical development thus far have all been N-nucleoside derivatives. Herein, we report the discovery of a C-nucleoside class of NS5B inhibitors. Exploration of adenosine analogs in this class identified 1′-cyano-2′-C-methyl 4-aza-7,9-dideaza adenosine as a potent and selective inhibitor of NS5B. A monophosphate prodrug approach afforded a series of compounds showing submicromolar activity in HCV replicon assays. Further pharmacokinetic optimization for sufficient oral absorption and liver triphosphate loading led to identification of a clinical development candidate GS-6620. In a phase I clinical study, the potential for potent activity was demonstrated but with high intra- and interpatient pharmacokinetic and pharmacodynamic variability.

METHODS FOR TREATING HCV

This invention relates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions.

1'-SUBSTITUTED-CARBA-NUCLEOSIDE PRODRUGS FOR ANTIVIRAL TREATMENT

Provided are prodrugs of pyrrolo[l,2-f][l,2,4]triazin-7-yl nucleoside phosphates wherein the 1 '' position of the nucleoside sugar is substituted with CN. The compounds, compositions, and methods provided are useful for the treatment Hepatitis C infections.