(2'R)-2'-Deoxy-2'-fluoro-2'-methyluridine
[CAS# 863329-66-2]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: (2'R)-2'-Deoxy-2'-fluoro-2'-methyluridine
• Synonyms: RO 2433; PSI-6206; 1-((2R,3R,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
• Molecular Formula: C₁₀H₁₃FN₂O₅
• Molecular Weight: 260.22
• CAS Registry Number: 863329-66-2
• EC Number: 810-481-6
• SMILES: C[C@]1([C@@H]([C@H](O[C@H]1N2C=CC(=O)NC2=O)CO)O)F

Properties

• Density: 1.6±0.1 g/cm³, Calc.^*, 1.55 gmL
• Melting point: 237-238 °C
• Index of Refraction: 1.596, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovery and Applications

(2'R)-2'-Deoxy-2'-fluoro-2'-methyluridine is a modified nucleoside that plays a significant role in medicinal chemistry, particularly in antiviral and anticancer research. This compound is an analogue of uridine, characterized by the addition of a fluoro and a methyl group at the 2' position of the sugar moiety. Its molecular formula is C10H12F2N2O5, and it is often abbreviated as 2'-F-MU. The synthesis of (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine began in the late 20th century as researchers sought to develop new nucleoside analogues with enhanced biological activity.

The discovery of (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine emerged from the need for effective antiviral agents, particularly against viral infections such as HIV and hepatitis. The incorporation of fluorine into nucleoside analogues has been shown to enhance their metabolic stability and inhibit viral polymerases, thereby improving their therapeutic potential. In various studies, (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine has demonstrated promising antiviral activity, making it a valuable compound for further development in the field of antiviral drug design.

In addition to its antiviral applications, (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine has also been investigated for its potential anticancer properties. Nucleoside analogues are known to interfere with DNA synthesis and repair mechanisms, leading to cell death in rapidly dividing cancer cells. The structural modifications in (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine provide it with unique interactions with nucleoside transporters and polymerases, enhancing its ability to selectively target cancer cells while minimizing effects on normal cells.

Research on (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine has also focused on its use in combination therapies, where it can be administered alongside other antiviral or anticancer agents to enhance overall efficacy. Studies have shown that this nucleoside analogue can synergize with existing antiviral medications, providing an avenue for improved treatment regimens for viral infections. Similarly, in cancer research, combining (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine with other chemotherapeutic agents has yielded promising results in preclinical models.

Despite its potential, further research is necessary to fully understand the pharmacokinetics and toxicology of (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine. Ongoing studies aim to optimize its formulation and delivery mechanisms, ensuring maximum efficacy while minimizing side effects. Regulatory assessments will also be crucial in determining its safety profile for clinical use.

In conclusion, (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine represents a significant advancement in the development of nucleoside analogues with applications in antiviral and anticancer therapies. Its unique structural properties and biological activities make it a promising candidate for further exploration in drug development.

References

2023. Antiviral drug recognition and elevator-type transport motions of CNT3. Nature Chemical Biology, 20(3).
DOI: 10.1038/s41589-024-01559-8

2017. The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-α-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors. Bioorganic & Medicinal Chemistry Letters, 27(18).
DOI: 10.1016/j.bmcl.2017.08.029

2007. Characterization of the metabolic activation of hepatitis C virus nucleoside inhibitor beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) and identification of a novel active 5'-triphosphate species. The Journal of Biological Chemistry, 282(41).
DOI: 10.1074/jbc.M705274200