HBV-IN-4

• CAT Number: I045761
• CAS Number: 2305897-84-9
• Molecular Formula: C24H19ClFN5O3
• Molecular Weight: 479.89
• Purity: ≥95%
• Synonyms: 4-[[4-[5-chloro-6-(2,3-dihydroxypropylamino)-2-fluoropyridin-3-yl]-1-oxophthalazin-2-yl]methyl]benzonitrile
• InChI: InChI=1S/C24H19ClFN5O3/c25-20-9-19(22(26)29-23(20)28-11-16(33)13-32)21-17-3-1-2-4-18(17)24(34)31(30-21)12-15-7-5-14(10-27)6-8-15/h1-9,16,32-33H,11-13H2,(H,28,29)
• InChIKey: WTCNPITUIDRZKR-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)C(=NN(C2=O)CC3=CC=C(C=C3)C#N)C4=CC(=C(N=C4F)NCC(CO)O)Cl

HBV-IN-4, a phthalazinone derivative, is a potent and orally active HBV DNA replication inhibitor with an IC50 of 14 nM. HBV-IN-4 induces the formation of genome-free capsids and has potent anti-HBV potencies[1].
HBV-IN-4 (compound 19f; 0-1 μM; 8 days) treatment inhibits the various forms (relaxed circular [rc] and single-stranded [ss] HBV DNA) in a dose-dependent manner in HepG2.2.15 cells. HBV-IN-4 treatment could also reduce capsidassociated DNAs dose-dependently. HBV-IN-4 could induce the formation of genome-free capsids, including a phenotype of faster-migrating ones[1].
HBV-IN-4 (Compound 19f; 50-150 mg/kg; oral administration; twice a day; for 4 weeks; Balb/c male mice) treatment achieves 2.67 log viral load reduction in AAV-HBV/mouse model[1].
HBV-IN-4 (compound 19f) exhibits favorable drug characteristics with low plasma clearance (CL=4.1 mL/min/kg), excellent drug exposure (AUC0-t=49 744 h•ng/L), T1/2 (2.15 hours) and oral bioavailability (F=60.4%) using 20 mg/kg oral administration in mice. HBV-IN-4 also shows good distribution in liver exposure[1].

Reference

[1]. Wuhong Chen, et al. Discovery of Phthalazinone Derivatives as Novel Hepatitis B Virus Capsid Inhibitors. J Med Chem. 2020 Jul 21.
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