Baloxavir marboxil
[CAS# 1985606-14-1]

Identification

• Classification: API >> Other chemicals
• Name: Baloxavir marboxil
• Synonyms: ({(12aR)-12-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-6,8-dioxo-3,4,6,8,12,12a-hexahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazin-7-yl}oxy)methyl methyl carbonate; Baloxavir marboxil; S 033188; Xofluza
• Molecular Formula: C₂₇H₂₃F₂N₃O₇S
• Molecular Weight: 571.55
• CAS Registry Number: 1985606-14-1
• EC Number: 862-996-0
• SMILES: COC(=O)OCOC1=C2C(=O)N3CCOC[C@H]3N(N2C=CC1=O)[C@H]4C5=C(CSC6=CC=CC=C46)C(=C(C=C5)F)F

Properties

• Solubility: Insoluble (4.7E^-4 g/L) (25 ºC), Calc.^*
• Density: 1.57±0.1 g/cm³ (20 ºC 760 Torr), Calc.^*
• Index of Refraction: 1.696, Calc.^*
• Boiling Point: 712.8±70.0 ºC (760 mmHg), Calc.^*
• Flash Point: 384.9±35.7 ºC, Calc.^*

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

Safety Data

• Hazard Symbols: GHS09 Warning
• Hazard Statements: H411
• Precautionary Statements: P273-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411

Discovory and Applicatios

Baloxavir marboxil is an antiviral medication developed for the treatment of influenza. It represents a new class of antiviral drugs known as the endonuclease inhibitors, targeting the influenza virus’s RNA polymerase to prevent the replication of the virus. Approved for use in both influenza A and B infections, baloxavir marboxil has demonstrated effectiveness in reducing the duration of flu symptoms, particularly when administered early in the course of infection. Its discovery and development mark a significant advancement in the fight against influenza, especially given the growing concern about antiviral resistance and the limitations of existing treatments.

The discovery of baloxavir marboxil emerged from efforts to develop a more efficient antiviral treatment for influenza. Traditional antiviral drugs such as oseltamivir (Tamiflu) and zanamivir (Relenza) inhibit the neuraminidase enzyme of the virus, which plays a role in the release of viral particles from infected cells. However, these drugs often require early administration to be most effective and are less effective once the infection has progressed. Researchers at Shionogi & Co., Ltd. identified a new target within the influenza virus, the endonuclease activity of the viral polymerase, which is essential for the virus’s replication. Inhibiting this enzyme would halt viral replication at an earlier stage, offering a potential advantage over other antiviral agents.

Baloxavir marboxil works by binding to the endonuclease active site of the influenza virus's RNA polymerase complex, inhibiting the cap-snatching process. This process is necessary for the virus to acquire the "caps" required for mRNA transcription, thereby halting viral replication. This mechanism of action is different from that of traditional influenza treatments, which focus on the viral surface proteins. By acting early in the replication cycle, baloxavir marboxil can potentially reduce the severity and duration of symptoms even when administered several days after symptom onset.

In clinical trials, baloxavir marboxil demonstrated strong efficacy in reducing the duration of flu symptoms when compared to placebo or oseltamivir, particularly when administered within 48 hours of symptom onset. One of its key advantages is that it can be taken as a single dose, making it more convenient for patients compared to other antiviral medications that require a course of treatment over several days. The drug has also shown activity against various strains of influenza, including those resistant to other antiviral agents, further expanding its potential as a treatment option.

Baloxavir marboxil received approval from the U.S. Food and Drug Administration (FDA) in 2018 for the treatment of acute uncomplicated influenza in patients 12 years and older. It has since been approved in several other countries and is included in guidelines for the treatment of influenza. Its approval was based on the results of phase III clinical trials, which demonstrated that it significantly reduced the duration of influenza symptoms and viral shedding compared to placebo. It was also found to be well-tolerated, with a safety profile similar to that of placebo.

In addition to its use in the treatment of influenza, baloxavir marboxil is being investigated for its potential use in the prevention of influenza, as well as its effectiveness against other respiratory viruses. Researchers are exploring the possibility of using it in combination with other antiviral agents or in populations at high risk for complications from influenza, such as the elderly or immunocompromised individuals.

In conclusion, baloxavir marboxil represents a promising addition to the antiviral arsenal against influenza. Its novel mechanism of action, convenient dosing regimen, and effectiveness against a broad range of influenza strains make it a valuable tool in the management of this common viral infection. As influenza continues to present a significant public health challenge, baloxavir marboxil offers hope for more effective and convenient treatment options.

References

2024. Drug resistance and possible therapeutic options against influenza A virus infection over past years. *Archives of Microbiology*.
DOI: 10.1007/s00203-024-04181-3

2024. A cost-effectiveness analysis of reduced viral transmission with baloxavir marboxil versus oseltamivir or no treatment for seasonal and pandemic influenza management in the United Kingdom. *Expert Review of Pharmacoeconomics & Outcomes Research*.
DOI: 10.1080/14737167.2024.2365421

2024. FOUR-WEEK ORAL ADMINISTRATION OF BALOXAVIR MARBOXIL AS AN ANTI-INFLUENZA VIRUS DRUG SHOWS NO TOXICITY IN CHICKENS. *Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians*.
DOI: 10.1638/2023-0103

2024. Discovery of baloxavir sodium as a novel anti-CCHFV inhibitor: Biological evaluation of in vitro and in vivo. *Antiviral Research*.
DOI: 10.1016/j.antiviral.2024.105890

2024. Evaluating the Public Health and Health Economic Impacts of Baloxavir Marboxil and Oseltamivir for Influenza Pandemic Control in China: A Cost-Effectiveness Analysis Using a Linked Dynamic Transmission-Economic Evaluation Model. *PharmacoEconomics*.
DOI: 10.1007/s40273-024-01412-9