1422526-27-9

Basic information

• Product Name: C₁₁H₁₃Cl₂O₄P
• Synonyms: C₁₁H₁₃Cl₂O₄P
• CAS NO: 1422526-27-9
• Molecular Weight: 311.102
• Mol File: 1422526-27-9.mol

Chemical Properties

• CAS DataBase Reference: C₁₁H₁₃Cl₂O₄P(CAS DataBase Reference)
• NIST Chemistry Reference: C₁₁H₁₃Cl₂O₄P(1422526-27-9)
• EPA Substance Registry System: C₁₁H₁₃Cl₂O₄P(1422526-27-9)

Safety Data

• Hazardous Substances Data: 1422526-27-9(Hazardous Substances Data)

Upstream product

• 20921-04-4 ethyl 3-(2-hydroxyphenyl)propanoate 
• 119-84-6 C₆H₄(CH₂CH₂C(O)O) 

Downstream Products

• 1412427-04-3 ethyl 3-(2-((chloro(((S)-1-ethoxy-1-oxopropan-2-yl)amino)-phosphoryl)oxy)phenyl)propanoate 
• 1412427-10-1 ethyl 3-(2-(((R)-(((2R,3R,4R,5R)-5-(2,6-diamino-9H-pu r in-9-y l )-3, 4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(((S)-1-ethoxy-1-oxopropan-2-yl)amino)phosphoryl)oxy)phenyl)propanoate 
• 1412427-15-6 (S)-ethyl 3-(2-(((((S)-1-ethoxy-1-oxopropan-2-yl)amino)(4-(methylthio)phenoxy)phosphoryl)oxy)phenyl)propanoate 
• 1412427-14-5 (R)-ethyl 3-(2-(((((S)-1-ethoxy-1-oxopropan-2-yl)amino)(4-(methylthio)phenoxy)phosphoryl)oxy)phenyl)propanoate 
• 1412427-17-8 (Sp)-ethyl 3-(2-(((((S)-1-ethoxy-1-oxopropan-2-yl)amino)(4-(methylsulfonyl)phenoxy)phosphoryl)oxy)phenyl)propanoate 
• 1412427-16-7 ethyl 3-(2-(((((S)-1-ethoxy-1-oxopropan-2-yl)amino)(4-(methylsulfonyl)phenoxy)phosphoryl)oxy)phenyl)propanoate 
• 1412427-19-0 ethyl 3-(2-(((((2R,3R,4R,5R)-5-(2-amino-6-(((benzyloxy)carbonyl)amino)-9H-purin-9-yl)-3-((tert-butyldimethylsilyl)oxy)-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)((1-ethoxy-1-oxopropan-2-yl)amino)phosphoryl)oxy)phenyl)propanoate 
• 1412427-29-2 ethyl 3-(2-(((S)-(((2R,3R,4R,5R)-5-(2-amino-6-(((benzyloxy)carbonyl)amino)-9H-purin-9-yl)-3-(((benzyloxy)carbonyl)oxy)-4-fluoro-4-methyltetrahydrofuran-2-yl)methoxy)(((S)-1-ethoxy-1-oxopropan-2-yl)amino)phosphoryl)oxy)phenyl)propanoate 
• 1412427-50-9 ethyl 3-(2-(((S)-(((2R,3R,4R,5R)-5-(2,6-diamino-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetra-hydrofuran-2-yl)methoxy)(((S)-1-ethoxy-1-oxopropan-2-yl)amino)phosphoryl)oxy)phenyl) propanoate 

Relevant articles and documents

Adenosine dioxolane nucleoside phosphoramidates as antiviral agents for human immunodeficiency and hepatitis B viruses

There are currently six nucleoside reverse transcriptase inhibitors (NRTI) that are FDA approved for human clinical use and these remain the backbone of current HIV therapy. In order for these NRTIs to be effective they need to be phosphorylated consecutively by cellular kinases to their triphosphate forms. Herein, we report the synthesis of C-6 modified (-)-β-d-(2R,4R)-1,3- dioxolane adenosine nucleosides and their nucleotides including our novel phosphoramidate prodrug technology. We have introduced a side chain moiety on the phenol portion of the phosphoramidate to reduce the toxicity potential. The synthesized phosphoramidates displayed up to a 3600-fold greater potency versus HIV-1 when compared to their corresponding parent nucleoside and were up to 300-fold more potent versus HBV. No cytotoxicity was observed up to 100 μM in the various cell systems tested, except for compounds 17 and 18, which displayed a CC50 of 7.3 and 12 μM, respectively, in Huh-7 cells. The improved and significant dual antiviral activity of these novel phosphoramidate nucleosides was partially explained by the increased intracellular formation of the adenosine dioxolane triphosphate.

β-D-2′-C-methyl-2,6-diaminopurine ribonucleoside phosphoramidates are potent and selective inhibitors of hepatitis C virus (HCV) and are bioconverted intracellularly to bioactive 2,6-diaminopurine and guanosine 5′-triphosphate forms

The conversion of selected β-d-2,6-diaminopurine nucleosides (DAPNs) to their phosphoramidate prodrug (PD) substantially blocks the conversion to the G-analog allowing for the generation of two bioactive nucleoside triphosphates (NTPs) in human hepatocytes. A variety of 2′-C-methyl DAPN-PDs were prepared and evaluated for inhibition of HCV viral replication in Huh-7 cells, cytotoxicity in various cell lines, and cellular pharmacology in both Huh-7 and primary human liver cells. The DAPN-PDs were pan-genotypic, effective against various HCV resistant mutants, and resistant variants could not be selected. 2′-C-Me-DAPN-TP and 2′-C-Me-GTP were chain terminators for genotype 1b HCV-pol, and single nucleotide incorporation assays revealed that 2′-C-Me-DAPN-TP was incorporated opposite U. No cytotoxicity was observed with our DAPN-PD when tested up to 50 μM. A novel, DAPN-PD, 15c, has been selected for further evaluation because of its good virologic and toxicologic profile and its ability to deliver two active metabolites, potentially simplifying HCV treatment.

PURINE MONOPHOSPHATE PRODRUGS FOR TREATMENT OF VIRAL INFECTIONS

The present invention is directed to compounds, compositions and methods for treating or preventing viral infections using nucleoside analog monophosphate prodrugs. More specifically, HCV, Norovirus, Saporovirus, Dengue virus, Chikungunya virus and Yellow fever in human patients or other animal hosts. The compounds are certain 2,6-diamino 2-C-methyl purine nucleoside monophosphate prodrugs and modified prodrug analogs, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show potent antiviral activity against HCV, Norovirus, Saporovirus, Dengue virus, Chikungunya virus and Yellow fever. This invention teaches how to modify the metabolic pathway of 2,6-diamino 2'-C-methyl purine and deliver nucleotide triphosphate(s) to polymerases at heretofore unobtainable therapeutically-relevant concentrations.