1064684-44-1

Basic information

• Product Name: Sofosbuvir
• Synonyms: PSI 7977; L-Alanine, N-[[p(S),2'R]-2'-deoxy-2'-fluoro-2'-methyl-p-phenyl-5'-uridylyl]-, 1-methylethyl ester; Psi-7977; (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate; sofosvuvir form6; sovaldi API; sofosbuvir form6; GS-7977; Sopropyl-(2S)-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl]-4-fluoro-3-hydroxy-4-methy-ltetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propanoate; Sofasbuvir
• CAS NO: 1064684-44-1
• Molecular Formula: C₂₂H₂₉FN₃O₉P
• Molecular Weight: 529.45
• Mol File: 1064684-44-1.mol
• Article Data: 17

Chemical Properties

• CAS DataBase Reference: Sofosbuvir(CAS DataBase Reference)
• NIST Chemistry Reference: Sofosbuvir(1064684-44-1)
• EPA Substance Registry System: Sofosbuvir(1064684-44-1)

Safety Data

• Hazardous Substances Data: 1064684-44-1(Hazardous Substances Data)

Usage

Description

Sofosbuvir, marketed under the brand name Sovaldi, is an antiviral medication specifically designed to treat chronic hepatitis C (Hep C). It functions by inhibiting the Hep C virus's NS5B RNA-dependent RNA polymerase enzyme, which is essential for viral replication. Sofosbuvir is incorporated into the viral RNA by the NS5B protein, leading to the termination of the viral replication process. This medication is highly effective when used alone or in combination with other antiviral drugs, significantly reducing the complications associated with Hep C, such as cirrhosis and liver cancer. Although generally well-tolerated, some common side effects include fatigue, headache, nausea, and difficulty sleeping.

Uses

Used in Pharmaceutical Industry:
Sofosbuvir is used as an antiviral agent for the treatment of chronic hepatitis C. It is effective in inhibiting the replication of the Hep C virus by targeting the NS5B RNA-dependent RNA polymerase enzyme, which is crucial for the virus's life cycle. This action leads to the termination of the viral chain, thereby reducing the viral load in the body and alleviating the symptoms and complications associated with Hep C.
Used in Combination Therapy:
Sofosbuvir is also used in combination with other antiviral medications to enhance the treatment efficacy for chronic hepatitis C. The combination therapy helps in achieving a higher rate of sustained virologic response (SVR), which is the gold standard for measuring the success of Hep C treatment. This approach is particularly beneficial for patients with genotype 1, 2, 3, or 4 of the Hep C virus, as it increases the chances of clearing the virus from the body and reducing the risk of liver-related complications.
Used in Hepatitis C Management:
Sofosbuvir plays a crucial role in the overall management of hepatitis C, as it helps in controlling the progression of the disease and preventing the development of severe liver complications. By effectively reducing the viral load, it contributes to the improvement of the patient's quality of life and reduces the burden on the healthcare system due to liver-related morbidities and mortalities.

Upstream product

• 261909-49-3 phenyl(isopropoxy-L-alaninyl) phosphorochloridate 
• 863329-66-2 2'-deoxy-2'-fluoro-2'-methyluridine 
• 879551-04-9 (3R,4R,5R)-3?fluoro?4?hydroxy?5?(hydroxymethyl)?3?methyltetrahydrofuran?2?one 
• 1160557-97-0 1-((2R,3R,4R,5R)-5-((tert-butyldimethylsilyloxy)methyl)-3-fluoro-4-hydroxy-3-methyl-tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione 
• 874638-98-9 N-(1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)benzamide 
• 39613-92-8 alanine isopropyl ester hydrochloride 
• 1500076-79-8 (2R)-2-deoxy-2-fluoro-2-methyl-α/β-D-erythro-pentofuranosyl chloride-3,5-dibenzoate 

Downstream Products

• 1190307-88-0 sofosbuvir 
• 1233335-78-8 (2S)-2-((((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(hydroxy)phosphorylamino)propanoic acid 

Relevant articles and documents

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.

Preparation method of sofosbuvir products in crystal and amorphous forms

The invention discloses a preparation method of sofosbuvir products in crystal and amorphous forms. The preparation method comprises the following steps: (1) preparation of sofebuvir: (2'R)-2'-deoxy-2'-fluorine-2'-methyluridine and N-[(S)-(2, 3, 4, 5, 6-pentafluorophenoxy) phenoxyphosphatidyl]-L-alanine isopropyl ester are used for preparing the crude product of sofebuvir under the action of a grignard reagent under anhydrous and anaerobic conditions; (2) preparation of sofosbuvir product in crystal form: the crude product of sofebuvir is placed in a ketones solvent, a decolorant is added, andthe sofosbuvir product in crystal form is obtained after dissolution, decolorization, crystallization and dryness; and (3) preparation of sofosbuvir product in amorphous form: the crude product of sofebuvir is placed in the ketones solvent, the decolorant is added, and the sofosbuvir product in amorphous form is obtained after dissolution, decolorization, crystallization, pulverization and dryness. The preparation method has the advantages of being simple and practicable, strong in operability, less in waste generation and lower in cost, and effectively solves deficiencies existing in the existing preparation method for the sofosbuvir product in crystal form.

PROCESS FOR THE PREPARATION OF SOFOSBUVIR

The present invention relates to a process for the synthesis of Sofosbuvir of formula (I) comprising the selective mono-deacetylation reaction of a compound of formula (V) to obtain a compound of formula (IV).