143157-27-1

Usage

Uses

Used in Pharmaceutical Industry:
2',2'-Difluoro-2'-deoxyuridine 3',5'-Dibenzoate is used as a protective agent for the Gemcitabine metabolite, 2',2'-difluoro-2'-deoxyuridine, to enhance the stability and effectiveness of Gemcitabine in treating various types of cancer and viral infections. By protecting the metabolite from degradation, 2',2'-Difluoro-2'-deoxyuridine 3',5'-Dibenzoate allows for a more efficient delivery and utilization of the active drug, leading to improved therapeutic outcomes.
Used in Anticancer Applications:
In the field of oncology, 2',2'-Difluoro-2'-deoxyuridine 3',5'-Dibenzoate plays a crucial role in the development and administration of Gemcitabine-based therapies. It helps maintain the integrity of the Gemcitabine metabolite, ensuring that the drug can effectively target and inhibit cancer cell growth, ultimately contributing to the treatment of various types of cancer.
Used in Antiviral Applications:
Beyond its applications in cancer treatment, 2',2'-Difluoro-2'-deoxyuridine 3',5'-Dibenzoate also plays a role in antiviral therapies. As a protective agent for the Gemcitabine metabolite, it helps to maintain the stability and efficacy of the drug when used to treat viral infections, such as cytomegalovirus (CMV) and other viral diseases.

Upstream product

• 134877-42-2 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-diphenylmethyl ester-1-methanesulfonate 
• 10457-14-4 O,O'-bis-(trimethylsilyl)uracil 
• 890044-84-5 (2R,3R)-5-acetoxy-2-((benzoyloxy)methyl)-4,4-difluorotetrahydrofuran-3-yl benzoate 
• 134877-42-2 3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-1-O-methanesulfonyl-D-erythro-pentofuranose 
• 908337-63-3 2¹-deoxy-2¹,2¹-difluoro-3,5-bis-O-benzoyl-D-ribose trichloroacetimidate 
• 66-22-8 uracil 
• 98-88-4 benzoyl chloride 
• 114248-23-6 Deoxydifluorouridine 
• 95058-81-4 gemcitabine 
• 1445381-44-1 (2R,3R,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-2-((benzoyloxy)methyl)-4,4-difluorotetrahydrofuran-3-yl benzoate 
• 122111-03-9 gemcitabine hydrochloride 

Downstream Products

• 114248-23-6 Deoxydifluorouridine 
• 1445381-68-9 C₃₁H₃₁F₂N₃O₅ 

Relevant academic research and scientific papers

Influence of 4′-Substitution on the Activity of Gemcitabine and Its ProTide against VZV and SARS-CoV-2

In addition to its therapeutic value as a chemotherapy drug, gemcitabine is of ongoing interest to the scientific community for its broad-spectrum antiviral activity. Herein the synthesis of 4′-methoxy- and 4′-fluoro-substituted gemcitabine analogues along with their phosphoramidate prodrugs is described. Among these derivatives, 4′-fluorogemcitabine proved to be active against varicella zoster virus (VZV, TK+ strain) with an EC50 of 0.042 μM and produced significant cytotoxicity (CC50 = 0.11 μM). Upon derivatization of this trifluoro nucleoside as its prodrug, decreased anti-VZV activity was observed, but with a concomitantly improved selectivity index (SI = 36). When this prodrug was tested against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its antiviral activity (EC50 = 0.73 μM) was comparable to or slightly lower than its cytotoxic concentration in measurements of cell growth and cell morphology, respectively.

Novel derivatives of nucleosides

PURPOSE: A novel nucleoside derivative and a method for synthesizing the same are provided to ensure excellent bioavailability and to enable oral administration. CONSTITUTION: A novel nucleoside derivative is a compound of chemical formula 2. A method for preparing the compound of chemical formula 2 comprise a step of adding NaOMe or hydrogen ion to a compound of chemical formula 10. The compound of chemical formula 10 is prepared by adding LiN_3 to a compound of chemical formula 9.

A linear synthesis of gemcitabine

Gemcitabine, 2′-deoxy-2′,2′-difluorocytidine, is currently prescribed against a number of cancers. Here we report a linear synthesis of gemcitabine with a high-yielding direct conversion of 3,5-di-O-benzoyl-2-deoxy-2,2-difluororibose into the corresponding glycosyl urea as the key step, followed by conventional conversion to the cytosine base via the uracil derivative. The process proceeded with modest anomeric selectivity.

Discovery of 4′-chloromethyl-2′-deoxy-3′,5′-di- O -isobutyryl-2′-fluorocytidine (ALS-8176), A first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is a leading pathogen of childhood and is associated with significant morbidity and mortality. To date, ribavirin is the only approved small molecule drug, which has limited use. The only other RSV drug is palivizumab, a monoclonal antibody, which is used for RSV prophylaxis. Clearly, there is an urgent need for small molecule RSV drugs. This article reports the design, synthesis, anti-RSV activity, metabolism, and pharmacokinetics of a series of 4′-substituted cytidine nucleosides. Among tested compounds 4′-chloromethyl-2′-deoxy-2′-fluorocytidine (2c) exhibited the most promising activity in the RSV replicon assay with an EC50 of 0.15 μM. The 5′-triphosphate of 2c (2c-TP) inhibited RSV polymerase with an IC50 of 0.02 μM without appreciable inhibition of human DNA and RNA polymerases at 100 μM. ALS-8176 (71), the 3′,5′-di-O-isobutyryl prodrug of 2c, demonstrated good oral bioavailability and a high level of 2c-TP in vivo. Compound 71 is a first-in-class nucleoside RSV polymerase inhibitor that demonstrated excellent anti-RSV efficacy and safety in a phase 2 clinical RSV challenge study.

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.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

DIFLUORONUCLEOSIDES AND PROCESS FOR PREPARATION THEREOF

A stereoselective process for the preparation of a 2’,2’-difluronucleoside is provided. In the process, a protected 2’,2’-difluorofuranose is coupled with a base selected from the group consisting of pyrimidine and purine derivatives in the presence of a Lewis acid, wherein the protected 2’,2’-difluorofuranose has a 1-position leaving group and 3- and 5-position protecting groups, and, when the base comprises 1 or more oxygen atoms, the base is a protected base, wherein each oxygen atom is protected with a protecting group.