BALAPIRAVIR HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H30N6O8.ClH
Molecular Weight	530.959
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.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=RAJFQMDUVDHLII-PYZPAVLJSA-N

InChI=1S/C21H30N6O8.ClH/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);1H/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

Molecular Formula	ClH
Molecular Weight	36.461
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/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
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
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
Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients.	2012 Jan-Feb	22166557

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 16:16:54 GMT 2023` Edited by `admin` on `Fri Dec 15 16:16:54 GMT 2023`
Record UNII	C860V13650
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BALAPIRAVIR HYDROCHLORIDE

Official Name

English

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

Common Name

English

CYTIDINE, 4'-C-AZIDO-, 2',3',5'-TRIS(2-METHYLPROPANOATE), HYDROCHLORIDE (1:1)

Common Name

English

RO-4588161-001

Code

English

BALAPIRAVIR HYDROCHLORIDE [USAN]

Common Name

English

RO4588161-001

Code

English

BALAPIRAVIR HCL

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C25995