1496551-72-4

Usage

Uses

Used in Pharmaceutical Industry:
1-((2R,3R,4R,5R)-3-chloro-4-hydroxy-5-(hydroxyMethyl)-3-Methyltetrahydrofuran-2-yl)pyriMidine-2,4(1H,3H)-dione is used as a potential therapeutic agent for the treatment of various diseases. Its unique molecular structure allows it to interact with specific biological targets, making it a promising candidate for drug development.
Used in Antiviral Applications:
As a possible metabolite of Sofosbuvir, 1-((2R,3R,4R,5R)-3-chloro-4-hydroxy-5-(hydroxyMethyl)-3-Methyltetrahydrofuran-2-yl)pyriMidine-2,4(1H,3H)-dione is being investigated for its potential use in the treatment of hepatitis C. It is metabolized to the active antiviral agent 2''-deoxy-2''-α-fluoro-β-C-methyluridine-5''-monophosphate, which has shown effectiveness in combating the hepatitis C virus.
Used in Drug Development Research:
The compound's unique structure and potential biological activity make it an interesting subject for further research in drug development. It can be studied for its interactions with various biological targets and its potential to be modified or optimized for specific therapeutic applications.
Used in Chemical Synthesis:
Due to its complex structure, 1-((2R,3R,4R,5R)-3-chloro-4-hydroxy-5-(hydroxyMethyl)-3-Methyltetrahydrofuran-2-yl)pyriMidine-2,4(1H,3H)-dione can also be used as a starting material or intermediate in the synthesis of other complex organic compounds, potentially leading to the development of new drugs or chemical products.

Upstream product

• 31448-54-1 2'-C-methyluridine 
• 944476-40-8 (2R,3R,3aS,9aR)-3-hydroxy-2-(hydroxymethyl)-3a-methyl-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-6-one 
• 119410-95-6 1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylenetetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione 
• 879551-01-6 (4S,5R)-ethyl-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-meth-yl-1,3,2-dioxathiolane-4-carboxylate 2,2-dioxide 
• 83159-91-5 3,5-di-O-(tert-butyldimethylsilyl)-2-deoxy-D-ribono-1,4-lactone 
• 1496551-70-2 2'-deoxy-2'-chloro-2'-C-methyl-3',5'-di-O-benzoyl-N⁴-benzoylcytidine 
• 1496551-71-3 C₂₄H₂₁ClN₂O₇ 

Downstream Products

• 1613590-78-5 C₁₇H₁₅ClFIN₂O₅ 
• 1613590-79-6 C₁₇H₁₆ClFN₂O₆ 
• 1613590-91-2 C₂₂H₂₈ClFN₃O₉P 
• 1496551-77-9 MK-3682 
• 1496551-77-9 ((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-chloro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-D-alanine isopropyl ester 

Relevant academic research and scientific papers

Synthesis and Anti-HCV Activities of 4′-Fluoro-2′-Substituted Uridine Triphosphates and Nucleotide Prodrugs: Discovery of 4′-Fluoro-2′- C-methyluridine 5′-Phosphoramidate Prodrug (AL-335) for the Treatment of Hepatitis C Infection

We report the synthesis and biological evaluation of a series of 4′-fluoro-2′-C-substituted uridines. Triphosphates of the uridine analogues exhibited a potent inhibition of hepatitis C virus (HCV) NS5B polymerase with IC50 values as low as 27 nM. In an HCV subgenomic replicon assay, the phosphoramidate prodrugs of these uridine analogues demonstrated a very potent activity with EC50 values as low as 20 nM. A lead compound AL-335 (53) demonstrated high levels of the nucleoside triphosphate in vitro in primary human hepatocytes and Huh-7 cells as well as in dog liver following a single oral dose. Compound 53 was selected for the clinical development where it showed promising results in phase 1 and 2 trials.

Antiviral nucleoside phosphoramidate and pharmaceutical composition and applications thereof

The invention provides an antiviral nucleoside phosphoramidate and a pharmaceutical composition and applications thereof. The nucleoside phosphoramidate compound is prepared by connecting nucleoside with phosphate through phosphorus-oxygen bonds. The structural formulas of the nucleoside phosphoramidate compound are represented by a, a1, a2, b, b1, and b2. The invention also discloses stereoisomers, pharmaceutically acceptable salts, hydrates, solvates, or crystals of the nucleoside phosphoramidate compound. The anti-hepatitis C activity of the provided novel nucleoside phosphoramidate is obviously better than that of sofosbuvir used in clinic. On the saccharide ring, the fluorine atoms are replaced by chlorine atoms, and the cytotoxicity of measure cell lines is prominently reduced. By systematically modifying and optimizing the basic groups, saccharide rings, and prodrugs, the anti-hepatitis C activity of partial synthesized compounds is 2 to 10 times higher than that of sofosbuvir. At the same time, the key parts of metabolism are optimized, the metabolism stability and chemical stability of synthesized compounds in plasma are better, compared with those of sofosbuvir.

PROCESS FOR MAKING CHLORO-SUBSTITUTED NUCLEOSIDE PHOSPHORAMIDATE COMPOUNDS

The present invention is directed to a process for making Chloro-Substituted Nucleoside Phosphoramidate Compounds of formula (I): which are useful for the treatment and prophylaxis of HCV infection. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2′-α-chloro-2′-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors

Herein we describe the discovery of IDX21437 35b, a novel RP D-aminoacid-based phosphoramidate prodrug of 2′-α-chloro-2′-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells. Furthermore, due to its metabolic activation, 35b was efficiently processed in liver cells compared to other cell types, including human cardiomyocytes. The selected RP diastereoisomeric configuration of 35b was assigned by X-ray structural determination. 35b is currently in Phase II clinical trials for the treatment of HCV infection.

Deuterated HCV NS5b inhibitor nucleotide derivative and application thereof

The invention provides a deuterated HCV (Hepatitis C Virus) NS5b inhibitor nucleotide derivative or its pharmaceutically acceptable salts, stereoisomers, tautomer inhibitors and its application in preparation of drugs for treatment or prevention of HCV infection. The inhibitor is represented by a general formula I (shown in the description).

PROCESS FOR MAKING NUCLEOSIDE PHOSPHORAMIDATE COMPOUNDS

The present invention is directed to a process for making Nucleoside Phosphoramidate Compounds of formula (I): which are useful for the treatment and prophylaxis of HCV infection. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

PRODUCTION OF CYCLIC PHOSPHATE, PHOSPHORAMIDATE, THIOPHOSPHATE, AND PHOSPHONATE NUCLEOSIDE COMPOUNDS

Provided herein are methods for the production of cyclic phosphate, cyclic phosphoramidate, cyclic thiophosphate, and cyclic phosphonate nucleoside compounds. Also provided herein are compounds useful in the production of cyclic phosphate, cyclic phosphoramidate, cyclic thiophosphate, and cyclic phosphonate nucleoside compounds. In certain embodiments, the cyclic phosphate, cyclic phosphoramidate, cyclic thiophosphate, and cyclic phosphonate nucleoside compounds are of Formula (I): wherein: Base, RA, RB, X, R1 and R2 are as defined herein. The cyclic phosphate, cyclic phosphoramidate, cyclic thiophosphate, and cyclic phosphonate nucleoside compounds are useful in the treatment of viral infections, including hepatitis C virus infections in hosts in need thereof.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Picornavirus and/or Flaviviridae infection with one or more nucleosides, nucleotides and nucleotide analogs.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Coronaviridae virus, a Togaviridae virus, a Hepeviridae virus and/or a Bunyaviridae virus infection with one or more nucleosides, nucleotides and nucleotide analogs.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.