840506-39-0

Basic information

• Product Name: L-Alanine, N-[chloro(4-chlorophenoxy)phosphinyl]-, ethyl ester
• CAS NO: 840506-39-0
• Molecular Formula: C11H14Cl2NO4P
• Molecular Weight: 326.116
• Mol File: 840506-39-0.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: L-Alanine, N-[chloro(4-chlorophenoxy)phosphinyl]-, ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: L-Alanine, N-[chloro(4-chlorophenoxy)phosphinyl]-, ethyl ester(840506-39-0)
• EPA Substance Registry System: L-Alanine, N-[chloro(4-chlorophenoxy)phosphinyl]-, ethyl ester(840506-39-0)

Safety Data

• Hazardous Substances Data: 840506-39-0(Hazardous Substances Data)

Upstream product

• 1115-59-9 (S)-alanine ethyl ester hydrochloride 
• 772-79-2 4-chlorophenylphosphorodichloridate 

Downstream Products

• 1092106-30-3 2'-deoxyzebularine 5'-[4-chlorophenyl(ethoxy-L-alaninyl)]phosphate 
• 1092106-31-4 2'-deoxyzebularine 3',5'-bis[4-chlorophenyl(ethoxy-L-alaninyl)]phosphate 
• 1238579-54-8 C₂₃H₂₈ClN₄O₉PS 
• 1192265-18-1 C₂₂H₂₈ClN₆O₈P 
• 946511-13-3 ethyl (2S)-2-{[{[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl]methoxy}(4-chlorophenoxy)phosphoryl]amino}propanoate 

Relevant articles and documents

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.

Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine

The currently approved treatment for hepatitis C virus infections is a combination of Ribavirin and pegylated Interferon. It leads to a sustained virologic response in approximately only half of the patients treated. For this reason there is an urgent need of new therapeutic agents. 2′-C-Methylcytidine is the first nucleoside inhibitor of the HCV NS5B polymerase that was efficacious in reducing the viral load in patients infected with HCV. The application of a monophosphate prodrug approach based on unprecedented cyclic phosphoramidates is reported. Our SAR studies led to compounds that are efficiently converted to the active triphosphate in human hepatocytes.

CHEMICAL COMPOUNDS

Phosphoramidate derivatives of nucleotides and their use in the treatment of cancer are described. The base moieties of, for example, each of deoxyuridine, cytarabine, gemcitabine and citidine may be substituted at the 5-position. The phosphoramidate moiety has attached to the P atom an aryl-O moiety and an α-amino acid moiety. The α-amino acid moiety may correspond to or be derived from either a naturally occurring or a non-naturally occurring amino acid.