5-Fluoro-2-oxindole
[CAS# 56341-41-4]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: 5-Fluoro-2-oxindole
• Synonyms: 5-Fluorooxindole
• Molecular Formula: C₈H₆FNO
• Molecular Weight: 151.14
• CAS Registry Number: 56341-41-4
• EC Number: 638-803-9
• SMILES: C1C2=C(C=CC(=C2)F)NC1=O

Properties

• Density: 1.3±0.1 g/cm³, Calc.^*
• Melting point: 143-147 °C (Expl.)
• Index of Refraction: 1.560, Calc.^*
• Boiling Point: 307.2±42.0 °C (760 mmHg), Calc.^*
• Flash Point: 139.6±27.9 °C, Calc.^*

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H301-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

5-Fluoro-2-oxindole is an organic compound that belongs to the class of oxindole derivatives. It is an important building block in the field of medicinal chemistry due to its wide range of applications in drug design and synthesis. The compound has gained attention for its potential biological activities, making it a subject of extensive research in recent years. Its structural characteristics, which include a fluorine atom at the 5-position of the oxindole ring, contribute to its unique reactivity and interaction with biological systems.

The discovery of 5-fluoro-2-oxindole can be traced back to the exploration of oxindole derivatives in the early 20th century. Oxindole, a bicyclic compound consisting of an indole ring fused to a lactam, has long been studied for its biological activity, including its potential to act as an inhibitor of enzymes involved in key cellular processes. The introduction of a fluorine atom at the 5-position of the oxindole ring was likely a modification designed to enhance the compound's pharmacological properties, including its stability, bioavailability, and potency. Since then, 5-fluoro-2-oxindole has been synthesized and tested for its therapeutic potential in various areas, particularly in the development of novel drug candidates.

One of the most notable applications of 5-fluoro-2-oxindole is its role as a precursor in the synthesis of biologically active compounds. The fluorine atom in the 5-position can significantly alter the compound's interaction with biological targets, often improving the selectivity and efficacy of the resulting molecules. This has led to the use of 5-fluoro-2-oxindole in the development of new pharmaceuticals, particularly in the treatment of cancer, inflammation, and neurological disorders.

In cancer research, for instance, 5-fluoro-2-oxindole has been studied for its potential as a kinase inhibitor. Kinases are enzymes that play a critical role in regulating cellular processes such as growth, division, and survival. Dysregulation of kinase activity is a hallmark of many cancers, and compounds that can selectively inhibit specific kinases hold great promise for targeted cancer therapies. 5-Fluoro-2-oxindole derivatives have shown activity against certain kinases, making them candidates for further exploration in cancer treatment.

In addition to its potential in oncology, 5-fluoro-2-oxindole has been investigated for its anti-inflammatory properties. Inflammation is a central feature of many diseases, including autoimmune disorders, cardiovascular diseases, and neurodegenerative conditions. Compounds that can modulate the inflammatory response are of significant interest in the development of new treatments. Studies have indicated that 5-fluoro-2-oxindole derivatives may help reduce inflammation by targeting key enzymes involved in the inflammatory process, such as cyclooxygenase-2 (COX-2).

Moreover, 5-fluoro-2-oxindole has also been studied for its potential neuroprotective effects. Neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, are characterized by the progressive degeneration of neurons and synaptic connections. Researchers have investigated 5-fluoro-2-oxindole as a potential therapeutic agent for these diseases, as it may exert protective effects on neurons by modulating signaling pathways involved in neuronal survival and function.

The synthesis of 5-fluoro-2-oxindole typically involves a variety of chemical methods, including halogenation reactions to introduce the fluorine atom at the 5-position, followed by cyclization to form the oxindole ring. The synthetic routes to 5-fluoro-2-oxindole can vary, with different strategies used to optimize yield, purity, and scalability for pharmaceutical production.

Despite its promising applications, the use of 5-fluoro-2-oxindole in drug development is not without challenges. The compound’s reactivity and the need for selective functionalization at specific positions of the oxindole ring can complicate its synthesis and optimization. Furthermore, as with many drug candidates, further studies are needed to fully assess its pharmacokinetic properties, including absorption, distribution, metabolism, and excretion (ADME), as well as its potential toxicity.

In conclusion, 5-fluoro-2-oxindole is a valuable compound in medicinal chemistry with significant potential in drug discovery. Its ability to modify biological activity through the presence of the fluorine atom makes it a versatile building block for the design of novel therapeutic agents. Ongoing research into its biological activities and synthesis methods continues to expand its applications in the development of drugs for cancer, inflammation, and neurodegenerative diseases.

References

2020. 5-Fluoro-2-oxindole enhances morphine’s antinociceptive effects in mice. Cellular and Molecular Neurobiology, 40(8).
DOI: 10.1007/s10571-020-00952-w

2011. Synthesis and antitumor activity of novel oxindole derivatives. European Journal of Medicinal Chemistry, 46(12).
DOI: 10.1016/j.ejmech.2011.10.009

2012. Design and synthesis of 5-fluoro-2-oxindole derivatives as potential anti-inflammatory agents. Medicinal Chemistry Research, 21(8).
DOI: 10.1007/s00044-012-0170-3