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Pimodivir

Product NamePimodivir
CAS1629869-44-8
MFC20H19F2N5O2
MW399.39
EINECS
MOL File1629869-44-8.mol

Chemical Properties

Density	1.501±0.06 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	Soluble in DMSO, not in water:100.0(Max Conc. mg/mL);250.38(Max Conc. mM)
form	A solid
pka	4.32±0.40(Predicted)
color	White to light yellow
InChIKey	JGPXDNKSIXAZEQ-SBBZOCNPSA-N
SMILES	C12CCC(CC1)[C@H](NC1C(F)=CN=C(C3C4=CC(F)=CN=C4NC=3)N=1)[C@H]2C(O)=O

Usage And Synthesis

Description

Pimodivir is an inhibitor of influenza virus polymerase basic protein 2 (PB2; K_D = <0.003 μM). It also binds to glycogen synthase kinase 3β (GSK3β; K_i = ^~1.6 μM) and inhibits the activity of Axl and calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) by greater than 50% in a panel of 65 human and rat kinases. Pimodivir decreases the replication of seven adamantine- and neuraminidase inhibitor-resistant strains of influenza virus A (EC₅₀s = <0.15-2.8 nM in a cell-based assay). It increases the antiviral activity of oseltamivir , zanamivir , and favipiravir (T-705; ) with 50% combination index (CI₅₀) values of 0.58, 0.64, and 0.89, respectively, in a cell-based assay. Pimodivir increases survival in a mouse model of intranasal influenza A infection when administered at doses of 1, 3, and 10 mg/kg twice per day.

Uses

Pimodivir is an orally bioavailable azaindole inhibitor of influenza PB2.

in vivo

Pimodivir (2, 6, and 20 mg/kg/day, p.o.) and GS 4071 (20 mg/kg/day) completely prevent death in the H1N1pdm virus infection in mice. Pimodivir (20 mg/kg/day) is more effective than GS 4071 (20 mg/kg/day) in improving body weight and reducing the severity of lung infection^[1].
Moreover, Pimodivir (VX-787) shows 100% survival in a +48 h delay to treatment mouse influenza model at 10, 3 and 1 mpk (BID × 10 days) whereas the SOC, GS 4071, provide no survival benefit in this model at 10 mpk^[3].
Pimodivir (VX-787; 1, 3, or 10 mg/kg, bid) provided complete survival, with a dose-dependent reduction in BW loss of the mice^[4].

References

[1] MICHAEL P. CLARK*. Discovery of a Novel, First-in-Class, Orally Bioavailable Azaindole Inhibitor (VX-787) of Influenza PB2[J]. Journal of Medicinal Chemistry, 2014, 57 15: 6668-6678. DOI: 10.1021/jm5007275
[2] RANDAL A BYRN. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit.[J]. Antimicrobial Agents and Chemotherapy, 2015: 1569-1582. DOI: 10.1128/aac.04623-14

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