| Stereochemistry | ABSOLUTE |
| Molecular Formula | C29H37N5O3 |
| Molecular Weight | 503.6358 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCC1=CC(CC[C@@]2(CC(O)=C(CC3=NN4C(=N3)N=C(C)C=C4C)C(=O)O2)C5CCCC5)=CC(CC)=N1
InChI
InChIKey=SLVAPEZTBDBAPI-GDLZYMKVSA-N
InChI=1S/C29H37N5O3/c1-5-22-14-20(15-23(6-2)31-22)11-12-29(21-9-7-8-10-21)17-25(35)24(27(36)37-29)16-26-32-28-30-18(3)13-19(4)34(28)33-26/h13-15,21,35H,5-12,16-17H2,1-4H3/t29-/m1/s1
| Molecular Formula | C29H37N5O3 |
| Molecular Weight | 503.6358 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Filibuvir (PF-868554), being developed by Pfizer, is an orally administered, non-nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase for the potential treatment of chronic hepatitis C (HCV) infection. Filibuvir is a potent and specific inhibitor of the virally encoded NS5B polymerase, and inhibited genotype 1 sub genomic HCV replication in the cell-based replicon system. In phase I and a IIa clinical trial in treatment-naïve patients infected with genotype 1 HCV, filibuvir monotherapy or in combination with pegylated IFNα2a/ribavirin (the standard of care [SoC] for HCV infection) for up to 4 weeks significantly reduced HCV RNA levels compared with placebo or SoC alone. However, company stopped development of the drug and the decision to halt development of the non-nucleoside polymerase inhibitor, which was in mid-stage testing, was not related to any safety issues.
Originator
Approval Year
Doses
Sourcing
PubMed
Patents
Sample Use Guides
Treatment-naïve, HCV genotype-1 patients were randomized to receive filibuvir 300 or 600 mg twice daily (BID) or placebo plus pegIFN (180 μg/wk) and ribavirin (1,000/1,200 mg BID) for 24 weeks. Filibuvir patients who achieved defined response through week 24 discontinued therapy at week 24. All other patients continued on open-label pegIFN/ribavirin through week 48. The primary endpoint was the proportion of patients who achieved sustained virologic response (SVR) defined as HCV RNA < 15 IU/mL at end of treatment (weeks 24 or 48) and week 72.
Route of Administration:
Oral
The ability of PF-00868554 to inhibit HCV RNA replication was evaluated against sub genomic replicons derived from the 1bCon1 and 1aH77 strains in replicon assays using the luciferase reporter end point. PF-00868554 demonstrated strong antiviral activity against the 1bCon1 replicon, with a mean EC50 of 0.075 uM, and reduced activity against the 1aH77 replicon, with a mean EC of 0.39 uM. The cytotoxicity of PF-00868554 was determined by the XTT assay with various human cell lines, including Huh7, HepG2, HeLa, and HEK293 cells, after 3 days of incubation. PF-00868554 demonstrated little or no cytopathic effects in multiple cell lines, up to the highest concentration of compound evaluated, with 50% cytotoxicity concentration values of more than 320 uM.
