BALAPIRAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H30N6O8
Molecular Weight	494.4983
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C(=O)OC[C@]1(O[C@H]([C@H](OC(=O)C(C)C)[C@@H]1OC(=O)C(C)C)N2C=CC(N)=NC2=O)N=[N+]=[N-]

InChI

InChIKey=VKXWOLCNTHXCLF-DXEZIKHYSA-N

InChI=1S/C21H30N6O8/c1-10(2)17(28)32-9-21(25-26-23)15(34-19(30)12(5)6)14(33-18(29)11(3)4)16(35-21)27-8-7-13(22)24-20(27)31/h7-8,10-12,14-16H,9H2,1-6H3,(H2,22,24,31)/t14-,15+,16-,21-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C21H30N6O8
Molecular Weight	494.4983
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18828074 | https://www.ncbi.nlm.nih.gov/pubmed/16316989 | https://www.ncbi.nlm.nih.gov/pubmed/22166557 | https://www.ncbi.nlm.nih.gov/pubmed/22807519 | https://www.ncbi.nlm.nih.gov/pubmed/26596942 | https://www.ncbi.nlm.nih.gov/pubmed/22166557https://www.ncbi.nlm.nih.gov/pubmed/16316989 | https://www.ncbi.nlm.nih.gov/pubmed/19778160

R1479 (4′-azidocytidine) is a specific inhibitor of hepatitis C virus (HCV) replication. 4′-azidocytidine triphosphate is an inhibitor of native HCV replicase and recombinant HCV polymerase (NS5B). Balapiravir (R1626) is the tri-isobutyrate ester prodrug of R1479 under clinical development to improve exposure of R1479 upon oral administration.

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/18828074 \| https://www.ncbi.nlm.nih.gov/pubmed/16316989	Inhibitor 8297		40.0 nM [Ki]
Hepatitis C virus NS5B RNA-dependent RNA polymerase 14 Target ID: CHEMBL5375 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16316989	Inhibitor 8297		40.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Hepatitis C 42 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18828074	Primary	Phase II 1132	Unknown Approved Use Unknown
Dengue virus infection 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22807519	Primary	Phase I 428	Unknown Approved Use Unknown
Hepatitis C 42 Sources: http://adisinsight.springer.com/drugs/800018944	Primary	Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 22	dCK 3 CYPs 33 UCK1 3	CYPs 12

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYPs 28	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/18553458/	no
CYPs 28	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18553458/	no

Drug as victim

Target	Modality	Activity
CYPs 33	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18553458/	no
dCK 3	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18003608/	yes [Km 23 uM]
UCK1 3	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19055482/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00DEJW	https://www.1pchem.com/search?query=1P00DEJW
AK Scientific	3995AH	https://aksci.com/item_detail.php?cat=3995AH
Achemo Scientific Limited	AC-75364	http://www.achemo.com/search/?Keyword=AC-75364
KeyOrganics	AS-56761	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56761
Lab Network	LN01342751	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342751
Lab Seeker	SC-94848	http://www.labseeker.com/search.php?keywords=SC-94848&category=0
LabSeeker	SC-94848	http://www.labseeker.com/search.php?keywords=SC-94848&category=0
MedChem Express	HY-10444	https://www.medchemexpress.com/search.html?q=HY-10444&ft=&fa=&fp=
MolPort	MolPort-028-720-591	https://www.molport.com/shop/molecule-link/MolPort-028-720-591
Molnova	M14594	https://www.molnova.com/en/serch-list.html?keywords=M14594
eMolecules	44811737	https://orderbb.emolecules.com/search/#?query=44811737
mcule	MCULE-2702719304	https://mcule.com/MCULE-2702719304/
mcule	MCULE-4346372188	https://mcule.com/MCULE-4346372188/

PubMed

Title	Date	PubMed
Synthesis and anti-HIV activity of 4'-azido- and 4'-methoxynucleosides.	1992 Apr 17	1573638
The novel nucleoside analog R1479 (4'-azidocytidine) is a potent inhibitor of NS5B-dependent RNA synthesis and hepatitis C virus replication in cell culture.	2006 Feb 17	16316989
Design, synthesis, and antiviral properties of 4'-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479.	2007 May 1	17317178
Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C.	2008 Aug	18553458
2'-deoxy-4'-azido nucleoside analogs are highly potent inhibitors of hepatitis C virus replication despite the lack of 2'-alpha-hydroxyl groups.	2008 Jan 25	18003608
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
R-1626, a specific oral NS5B polymerase inhibitor of hepatitis C virus.	2008 Oct	18828074
Amidinoanthracyclines - a new group of potential anti-hepatitis C virus compounds.	2009 Apr	19199832
The design, synthesis, and antiviral activity of 4'-azidocytidine analogues against hepatitis C virus replication: the discovery of 4'-azidoarabinocytidine.	2009 Jan 8	19055482
Substituted imidazopyridines as potent inhibitors of HCV replication.	2009 May	19303654
The design, synthesis, and antiviral activity of monofluoro and difluoro analogues of 4'-azidocytidine against hepatitis C virus replication: the discovery of 4'-azido-2'-deoxy-2'-fluorocytidine and 4'-azido-2'-dideoxy-2',2'-difluorocytidine.	2009 May 14	19341305
Synthesis of new acridone derivatives, inhibitors of NS3 helicase, which efficiently and specifically inhibit subgenomic HCV replication.	2010 Apr 22	20337460
PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication.	2010 Aug	20516278
2'-Deoxy-2'-spirocyclopropylcytidine revisited: a new and selective inhibitor of the hepatitis C virus NS5B polymerase.	2010 Nov 25	21033671
Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients.	2012 Jan-Feb	22166557
Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.	2014	24419349
Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir.	2014 Feb	24257621

Patents

Sample Use Guides

In Vivo Use Guide

The phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in hepatitis C genotype 1 patients. Treatment-naive genotype 1 patients were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 µg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.

Route of Administration: Oral

In Vitro Use Guide

R1479 (4'-azidocytidine) is a specific inhibitor of HCV replication in the HCV subgenomic replicon system (IC(50) = 1.28 microM). R1479 showed no effect on cell viability or proliferation of HCV replicon or Huh-7 cells at concentrations up to 2 mM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:14:12 GMT 2023` Edited by `admin` on `Fri Dec 15 16:14:12 GMT 2023`
Record UNII	VOT0LP7I9K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BALAPIRAVIR

Official Name

English

R1626

Code

English

Balapiravir [WHO-DD]

Common Name

English

RO-4588161

Code

English

RO4588161

Code

English

CYTIDINE, 4'-C-AZIDO-, 2',3',5'-TRIS(2-METHYLPROPANOATE)

Common Name

English

R-1626

Code

English

balapiravir [INN]

Common Name

English

4-AMINO-1-(4-C-AZIDO-2',3',5'-TRI-O-(2-METHYLPROPANOYL)-.BETA.-D-RIBOFURANOSYL)PYRIMIDIN- 2(1H)-ONE

Common Name

English

BALAPIRAVIR [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C281