Ziresovir
[CAS# 1422500-60-4]

Identification

• Classification: API >> Synthetic anti-infective drugs
• Name: Ziresovir
• Synonyms: N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxo-3,5-dihydro-2H-1?6,4-benzothiazepin-4-yl)-6-methylquinazolin-4-amine
• Molecular Formula: C₂₂H₂₅N₅O₃S
• Molecular Weight: 439.53
• CAS Registry Number: 1422500-60-4
• SMILES: CC1=CC2=C(C=C1)N=C(N=C2NCC3(COC3)N)N4CCS(=O)(=O)C5=CC=CC=C5C4

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 745.4±70.0 °C 760 mmHg (Calc.)^*
• Flash point: 404.6±35.7 °C (Calc.)^*
• Solubility: Soluble 100 mM in water (Expl.), Soluble 100 mM in water (Expl.)
• Index of refraction: 1.679 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319
• Safety Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovery and Applications

Ziresovir is a small-molecule antiviral drug developed primarily to inhibit the respiratory syncytial virus (RSV), a major cause of respiratory infections, especially in infants, young children, and older adults. Its discovery was driven by the urgent need for effective therapeutic agents to treat RSV infections, which can lead to severe respiratory illness and hospitalization.

Ziresovir functions as a fusion (F) protein inhibitor, targeting the RSV fusion glycoprotein that is essential for viral entry into host cells. By binding to the fusion protein, Ziresovir prevents the virus from fusing with the host cell membrane, thereby blocking viral replication early in the infection process. This mode of action is highly specific to RSV, which contributes to its potential effectiveness and safety.

The development of Ziresovir involved extensive medicinal chemistry optimization to enhance potency, selectivity, and pharmacokinetic properties suitable for oral administration. It has been evaluated in clinical trials where it demonstrated antiviral activity and a favorable safety profile. The oral bioavailability of Ziresovir is significant because it facilitates outpatient treatment, which is critical for managing RSV infections without requiring hospitalization.

In addition to its antiviral activity, Ziresovir has been investigated for its potential to reduce the severity and duration of RSV symptoms. Its targeted mechanism provides an advantage over nonspecific treatments, reducing the risk of resistance development and off-target effects.

Beyond RSV, Ziresovir’s discovery and design illustrate advances in rational drug design against viral fusion proteins, which are common targets in multiple viral families. This approach opens pathways for the development of similar antiviral agents against other respiratory viruses that rely on membrane fusion.

Overall, Ziresovir represents a significant advancement in antiviral therapy for RSV, offering a specific, orally available option to combat a virus responsible for considerable morbidity worldwide. Its discovery and clinical development reflect the progress in antiviral drug design, focusing on precise inhibition of viral entry mechanisms to improve treatment outcomes.

References

2019. Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor. Journal of Medicinal Chemistry, 62(12).
DOI: 10.1021/acs.jmedchem.9b00654

2023. Safety and efficacy of AK0529 in respiratory syncytial virus‐infected infant patients: A phase 2 proof‐of‐concept trial. Influenza and Other Respiratory Viruses, 17(7).
DOI: 10.1111/irv.13176

2024. Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection. The New England Journal of Medicine, 391(12).
DOI: 10.1056/NEJMoa2313551