NESBUVIR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H23FN2O5S
Molecular Weight	446.492
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=O)C1=C(OC2=C1C=C(C3CC3)C(=C2)N(CCO)S(C)(=O)=O)C4=CC=C(F)C=C4

InChI

InChIKey=WTDWVLJJJOTABN-UHFFFAOYSA-N

InChI=1S/C22H23FN2O5S/c1-24-22(27)20-17-11-16(13-3-4-13)18(25(9-10-26)31(2,28)29)12-19(17)30-21(20)14-5-7-15(23)8-6-14/h5-8,11-13,26H,3-4,9-10H2,1-2H3,(H,24,27)

HIDE SMILES / InChI

Molecular Formula	C22H23FN2O5S
Molecular Weight	446.492
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18559648 | http://www.pharmatimes.com/news/wyeth_and_viropharma_finally_give_up_on_hcv-796_987249

Nesbuvir (previously known as VB-19796 and HCV-796) is an inhibitor of hepatitis C NS5B RNA-dependent RNA polymerase. The drug was tested in phase II in patients with hepatitis C in combination with rebetol and peg-intron, however, its development was terminated due to 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/18559648	Inhibitor 8297		0.081 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatitis C 42 Sources: https://clinicaltrials.gov/ct2/show/NCT00367887	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677415	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677415	yes [IC50 10.684 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677415	yes [IC50 13.4504 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677415	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00FCH9	https://www.1pchem.com/search?query=1P00FCH9
ApexBio Technology	A3655	https://www.apexbt.com/catalogsearch/result/?q=A3655
BOC Sciences	691852-58-1	http://www.bocsci.com/description.asp?cas=691852-58-1
Chem Scene	CS-0689	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0689
ChemShuttle	157192	https://www.chemshuttle.com/catalogsearch/result/?q=157192
Debye Scientific	DA-33585	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-33585
Excenen	EX-A2110	http://www.excenen.com/searchresultlist.php?id=EX-A2110
MedChem Express	HY-14775	https://www.medchemexpress.com/search.html?q=HY-14775&ft=&fa=&fp=
MolPort	MolPort-023-293-555	https://www.molport.com/shop/molecule-link/MolPort-023-293-555
ShangHai Biochempartner	BCP14777	http://www.biochempartner.com/search_BCP14777
eMolecules	44811504	https://orderbb.emolecules.com/search/#?query=44811504
eNovation Chemicals	D501874	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501874&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6575655722	https://mcule.com/MCULE-6575655722/

PubMed

Title	Date	PubMed
Existence of hepatitis C virus NS5B variants naturally resistant to non-nucleoside, but not to nucleoside, polymerase inhibitors among untreated patients.	2008 Jun	18343801
The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors.	2008 May	18285474
Molecular mechanism of hepatitis C virus replicon variants with reduced susceptibility to a benzofuran inhibitor, HCV-796.	2008 Sep	18559648
Severe hepatocellular injury with apoptosis induced by a hepatitis C polymerase inhibitor.	2009 Apr	19098685
HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus.	2009 Mar	19072827
Substituted imidazopyridines as potent inhibitors of HCV replication.	2009 May	19303654
Inhibitors of hepatitis C virus polymerase: synthesis and characterization of novel 2-oxy-6-fluoro-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-benzamides.	2010 Apr 1	20219368
Mechanisms of activity and inhibition of the hepatitis C virus RNA-dependent RNA polymerase.	2010 Apr 30	20194503
The hepatitis C virus (HCV) NS4B RNA binding inhibitor clemizole is highly synergistic with HCV protease inhibitors.	2010 Jul 1	20486856
Cellular growth kinetics distinguish a cyclophilin inhibitor from an HSP90 inhibitor as a selective inhibitor of hepatitis C virus.	2012	22347373
MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants.	2012 Aug	22615282
Discovery of substituted N-phenylbenzenesulphonamides as a novel class of non-nucleoside hepatitis C virus polymerase inhibitors.	2012 Aug	22580131
In vitro efficacy of approved and experimental antivirals against novel genotype 3 hepatitis C virus subgenomic replicons.	2013 Nov	24013001
In vitro characterization of GSK2485852, a novel hepatitis C virus polymerase inhibitor.	2013 Nov	23939896
Restoration of the activated Rig-I pathway in hepatitis C virus (HCV) replicon cells by HCV protease, polymerase, and NS5A inhibitors in vitro at clinically relevant concentrations.	2013 Sep	23836176

Patents

Sample Use Guides

In Vivo Use Guide

Nesbuvir is administered at a dose of 500 mg, every 12 hours for 48 weeks (in combination with rebetol and peg-intron).

Route of Administration: Oral

In Vitro Use Guide

Cells bearing a genotype 1b HCV replicon were treated multiple times with 0.1 and 1 uM nesbuvir. At the end of the 16-day treatment, about 3.6 log10 and 4.2 log10 reductions of HCV RNA levels were observed, respectively. The concentration of the compound that inhibited 50% of the HCV RNA level was 9 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:33:18 UTC 2023` Edited by `admin` on `Fri Dec 15 16:33:18 UTC 2023`
Record UNII	EYK815W3Z8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NESBUVIR

Official Name

English

NESBUVIR [USAN]

Common Name

English

3-BENZOFURANCARBOXAMIDE, 5-CYCLOPROPYL-2-(4-FLUOROPHENYL)-6-((2-HYDROXYETHYL)(METHYLSULFONYL)AMINO)-N-METHYL-

Systematic Name

English

HCV-796

Code

English

HCV796

Code

English

5-Cyclopropyl-2-(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide

Systematic Name

English

nesbuvir [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C281