| Identification | Back Directory | [Name]
N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine | [CAS]
1422500-60-4 | [Synonyms]
AK0529
RO-0529
Ziresovir
N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine
4-Quinazolinamine, N-[(3-amino-3-oxetanyl)methyl]-2-(2,3-dihydro-1,1-dioxido-1,4-benzothiazepin-4(5H)-yl)-6-methyl-
4-(4-(((3-Aminooxetan-3-yl)methyl)amino)-6-methylquinazolin-2-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]thiazepine 1,1-dioxide | [Molecular Formula]
C22H25N5O3S | [MOL File]
1422500-60-4.mol | [Molecular Weight]
439.53 |
| Chemical Properties | Back Directory | [Boiling point ]
745.4±70.0 °C(Predicted) | [density ]
1.390±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 125 mg/mL (284.39 mM) | [form ]
Solid | [pka]
7.70±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Ziresovir (AK0529;RO-0529) is a potent, selective, and orally bioavailable respiratory syncytial virus (RSV) fusion (F) protein (RSV F) protein inhibitor. Ziresovir shows anti-RSV activity (EC50=3 nM) and highlights pharmacokinetics in animal species[1]. | [in vivo]
Ziresovir (12.5 mg/kg, 50 mg/kg; p.o.; twice daily; 4 d) results reduction of RSV titer in mouse lung[1].
Ziresovir (10 mg/kg; p.o.; single dose) exhibits good oral exposure and bioavailability?with F(%) of 32% in male Wistar-Han rats[1].
Ziresovir (150 mg/kg; p.o.; single dose) demonstrates a high tissue distribution to lung than plasma in CD-1 Mice[1].
Pharmacokinetics of Ziresovir in male Wistar-Han rats[1]
| Dose (mg/kg) | AUC0-24h(p.o.) (ng·h/mL) | CL (mL/min/kg) | T1/2(i.v.) (h) | Vss (L/kg) | F (%) | | 2 mg/kg (iv) or 10 mg/kg (po) | 906 | 58 | 1.2 | 3.9 | 32 |
Pharmacokinetics of Ziresovir in CD-1 Mice[1]| Dose (mg/kg) | AUC0-24h(p.o.) (μg·h/L) | tissue/lasma AUC0-24h ratio (μg·h/L) | T1/2 (h) | Tmax (h) | Cmax (μg/L) | | plasma | 8,380 | 1 | 1.02 | 0.25 | 5090 | | lung | 72,400 | 8.6 | 3.31 | 1 | 22700 |
| Animal Model: | Female BALB/c mice infected by RSV[1] | | Dosage: | 12.5 mg/kg, 50 mg/kg | | Administration: | Oral gavage; twice daily; 4 days | | Result: | Resulted >1 log unit of viral titer reduction in the lung of infected mice at the dose level as low as 12.5 mg/kg.?
Reduced viral titer to 1.9 log units compared to vehicle at 50 mg/kg dose. |
| [storage]
Store at -20°C | [References]
[1] Zheng X, et al. Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor. J Med Chem. 2019 Jul 11;62(13):6003-6014. DOI:10.1021/acs.jmedchem.9b00654 |
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