FILIBUVIR

Investigational

Details

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

Structure Search

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

HIDE SMILES / InChI

Molecular Formula	C29H37N5O3
Molecular Weight	503.6358
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21154154
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19307358 | http://www.firstwordpharma.com/node/1063595#axzz4RRTWaVYS

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

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatitis C virus NS5B RNA-dependent RNA polymerase 14 Target ID: CHEMBL5375 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19307358	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatitis C 42 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24927607	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
50274 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21488067	700 mg 2 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered:		FILIBUVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
38735 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21488067	700 mg 2 times / day single, oral dose: 700 mg route of administration: Oral experiment type: SINGLE co-administered:		FILIBUVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
291172 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21488067	700 mg 2 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered:		FILIBUVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
198507 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21488067	700 mg 2 times / day single, oral dose: 700 mg route of administration: Oral experiment type: SINGLE co-administered:		FILIBUVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.47 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21488067	700 mg 2 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered:		FILIBUVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2.12% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23183437	unknown, unknown		FILIBUVIR plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21488067	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/21488067	Sources: https://pubmed.ncbi.nlm.nih.gov/21488067

Sourcing

Vendor/Aggregator	ID	URL
Chem Scene	CS-0002461	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0002461
Compound Cloud	54708673
eMolecules	50426880	https://orderbb.emolecules.com/search/#?query=50426880
MedChem Express	HY-10118	https://www.medchemexpress.com/search.html?q=HY-10118&ft=&fa=&fp=
Molnova	M16368	https://www.molnova.com/en/serch-list.html?keywords=M16368
MolPort	MolPort-046-836-475	https://www.molport.com/shop/molecule-link/MolPort-046-836-475
MuseChem	I006602	https://www.musechem.com/product/I006602.html

PubMed

Title	Date	PubMed
A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV.	2014-06-14	24927607
Understanding the drug resistance mechanism of hepatitis C virus NS5B to PF-00868554 due to mutations of the 423 site: a computational study.	2014-04	24452008
Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.	2009-06	19307358
Discovery of (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a potent and orally available hepatitis C virus polymerase inhibitor.	2009-03-12	19209845

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:33:06 GMT 2025` Edited by `admin` on `Mon Mar 31 18:33:06 GMT 2025`
Record UNII	198J479Y2L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PF-868554

Preferred Name

English

FILIBUVIR

Official Name

English

PF-00868554

Code

English

Filibuvir [WHO-DD]

Common Name

English

(6R)-6-CYCLOPENTYL-6-(2-(2,6-DIETHYLPYRIDIN-4-YL)ETHYL)-3-((5,7-DIMETHYL(1,2,4)TRIAZOLO(1,5- A)PYRIMIDIN-2-YL)METHYL)-4-HYDROXY-5,6-DIHYDRO-2H-PYRAN-2-ONE

Systematic Name

English

2H-PYRAN-2-ONE, 6-CYCLOPENTYL-6-(2-(2,6-DIETHYL-4-PYRIDINYL)ETHYL)-3-((5,7-DIMETHYL(1,2,4)TRIAZOLO(1,5-A)PYRIMIDIN-2-YL)METHYL)-5,6-DIHYDRO-4-HYDROXY-, (6R)-

Systematic Name

English

FILIBUVIR [USAN]

Common Name

English

filibuvir [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C25995