Isavuconazole
[CAS# 241479-67-4]

Identification

• Classification: API >> Antibiotics
• Name: Isavuconazole
• Synonyms: 4-[2-[(1R,2R)-2-(2,5-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-thiazolyl]benzonitrile
• Molecular Formula: C₂₂H₁₇F₂N₅OS
• Molecular Weight: 437.47
• CAS Registry Number: 241479-67-4
• EC Number: 889-355-8
• SMILES: C[C@@H](C1=NC(=CS1)C2=CC=C(C=C2)C#N)[C@](CN3C=NC=N3)(C4=C(C=CC(=C4)F)F)O

Properties

• Solubility: 2 mg/mL (DMSO)
• Density: 1.38

Safety Data

• Hazard Symbols: GHS07;GHS08 Warning
• Risk Statements: H302-H312-H315-H319-H332-H361
• Safety Statements: P203-P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P318-P321-P330-P332+P317-P337+P317-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H312
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

Isavuconazole is a triazole antifungal agent recognized for its efficacy in treating various invasive fungal infections. The compound belongs to the class of azole antifungals, which function by inhibiting ergosterol synthesis, a critical component of fungal cell membranes.

The discovery of isavuconazole resulted from extensive research aimed at developing new antifungal agents with improved efficacy and safety profiles compared to existing treatments. The development of this compound involved a strategic approach to modify the chemical structure of earlier triazole derivatives to enhance antifungal activity and pharmacokinetic properties. Isavuconazole was specifically designed to overcome limitations such as poor solubility and drug-drug interactions that affected earlier triazole antifungals.

The synthesis of isavuconazole typically begins with the preparation of a triazole ring system, which is then substituted to optimize its antifungal properties. The final compound features a distinctive structure that allows it to effectively target and inhibit fungal lanosterol 14α-demethylase, an enzyme crucial for ergosterol biosynthesis. By inhibiting this enzyme, isavuconazole disrupts the fungal cell membrane, leading to cell death and resolution of infection.

Isavuconazole is primarily used in the treatment of invasive fungal infections, including invasive aspergillosis and mucormycosis. Its broad-spectrum antifungal activity makes it a valuable option for patients with weakened immune systems who are at high risk for these serious infections. The drug is also used as a prophylactic treatment to prevent fungal infections in certain high-risk populations.

One of the significant advantages of isavuconazole over other triazole antifungals is its favorable pharmacokinetic profile. The drug exhibits excellent oral bioavailability and has a long half-life, allowing for once-daily dosing. This profile not only enhances patient compliance but also provides effective and sustained antifungal activity. Additionally, isavuconazole has a lower potential for drug-drug interactions compared to other triazole agents, which is crucial for patients on complex medication regimens.

In clinical practice, isavuconazole has been shown to be effective in managing severe fungal infections, and its safety profile has been well-documented through extensive clinical trials. The compound has been integrated into treatment guidelines for invasive fungal infections, reflecting its importance in modern antifungal therapy.

Overall, isavuconazole represents a significant advancement in the field of antifungal therapy. Its development and application address critical needs in the management of invasive fungal infections, providing a valuable tool for clinicians and improving outcomes for patients with challenging fungal diseases.

References

2024. Diagnosis and Management of Infections in Diabetes Mellitus. *Management of Diabetic Complications*.
DOI: 10.1007/978-981-97-6406-8_25

2019. Therapeutic tools for oral candidiasis: Current and new antifungal drugs. *Medicina Oral, Patología Oral y Cirugía Bucal*, 24(2).
DOI: 10.4317/medoral.22978

2014. Isavuconazole Treatment of a Patient with Disseminated Mucormycosis. *Journal of Clinical Microbiology*, 52(3).
DOI: 10.1128/jcm.03176-13