U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C38H50N6O9S.H2O
Molecular Weight 784.9212
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GRAZOPREVIR

SMILES

C=C[C@]1([H])C[C@@]1(C(=NS(=O)(=O)C2CC2)O)N=C([C@]3([H])C[C@]4([H])CN3C(=O)[C@]([H])(C(C)(C)C)N=C(O)O[C@]5([H])C[C@@]5([H])CCCCCc6c(nc7cc(ccc7n6)OC)O4)O.O

InChI

InChIKey=RXSARIJMSJWJLZ-CIAYNJNFSA-N
InChI=1S/C38H50N6O9S.H2O/c1-6-22-19-38(22,35(47)43-54(49,50)25-13-14-25)42-32(45)29-18-24-20-44(29)34(46)31(37(2,3)4)41-36(48)53-30-16-21(30)10-8-7-9-11-27-33(52-24)40-28-17-23(51-5)12-15-26(28)39-27;/h6,12,15,17,21-22,24-25,29-31H,1,7-11,13-14,16,18-20H2,2-5H3,(H,41,48)(H,42,45)(H,43,47);1H2/t21-,22-,24-,29+,30-,31-,38-;/m1./s1

HIDE SMILES / InChI

Molecular Formula C38H50N6O9S
Molecular Weight 766.906
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Grazoprevir is a second generation NS3/4A protease inhibitor approved in the EU and the USA for the treatment of hepatitis C virus (HCV) genotypes 1 and 4 infections in adult patients in combination with elbasvir (C virus (HCV) NS5A inhibitor) as the fixed-dose combination product Zepatier with or without ribavirin. In phase III trials, 12 or 16 weeks of treatment with once-daily elbasvir/grazoprevir (fixed-dose tablet or as individual agents), taken with or without ribavirin, generally provided high rates of sustained virological response at 12 weeks (SVR12) in treatment-naive and -experienced adult patients with chronic HCV genotype 1a, 1b or 4 infection, including those with or without compensated cirrhosis, HIV co-infection, inherited blood disorders or chronic kidney disease or patients receiving opioid agonist therapy or of Japanese origin. Elbasvir/grazoprevir was generally well tolerated. Thus, elbasvir/grazoprevir, with or without ribavirin, represents an effective new option for the treatment of adults with chronic HCV genotype 1 and 4 infection, including a number of difficult-to-treat populations.

Originator

Curator's Comment:: # Merck

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZEPATIER

Approved Use

ZEPATIER is a fixed-dose combination product containing elbasvir, a hepatitis C virus (HCV) NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor, and is indicated for treatment of chronic HCV genotype 1 or 4 infection in adults. ZEPATIER is indicated for use with ribavirin in certain patient populations.

Launch Date

1453939200000
PubMed

PubMed

TitleDatePubMed
Identification of the E5 open reading frame of human papillomavirus type 16.
1988 Mar
Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor.
2012 Apr 12
MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants.
2012 Aug
Grazoprevir and Elbasvir in Patients with Genotype 1 Hepatitis C Virus Infection: A Comprehensive Efficacy and Safety Analysis.
2017
Unraveling the structural basis of grazoprevir potency against clinically relevant substitutions in hepatitis C virus NS3/4A protease from genotype 1a.
2017 Apr 14
Elbasvir/grazoprevir.
2017 Feb
Elbasvir/Grazoprevir (Zepatier) for Hepatitis C Virus Infection.
2017 Mar 15
Elbasvir/Grazoprevir: A Review in Chronic HCV Genotypes 1 and 4.
2017 May
Elbasvir/grazoprevir does not worsen renal function in patients with hepatitis C virus infection and pre-existing renal disease.
2017 Nov
Elbasvir/Grazoprevir Use in Postliver Transplantation Patients on Hemodialysis.
2017 Sep
Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study.
2017 Sep
Patents

Sample Use Guides

ZEPATIER is a two-drug, fixed-dose combination product containing 50 mg of elbasvir and 100 mg of grazoprevir in a single tablet. The recommended dosage of ZEPATIER is one tablet taken orally once daily with or without food
Route of Administration: Oral
In a cell-based replicon system, MK-5172 (Grazoprevir) inhibited HCV with EC50 values of 2 nM against genotype 1a, 0.5 nM against genotype 1b, 8 nM against genotype 2a and 13 nM against genotype 3. Also, MK-5172 is effective against HCV genotypes 1a, 2a, 1b, 2b and 3a.
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:44:18 UTC 2021
Edited
by admin
on Sat Jun 26 03:44:18 UTC 2021
Record UNII
4O2AB118LA
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GRAZOPREVIR
DASH   USAN  
USAN  
Official Name English
GRAZOPREVIR [ORANGE BOOK]
Common Name English
GRAZOPREVIR MONOHYDRATE
WHO-DD  
Common Name English
GRAZOPREVIR MONOHYDRATE [WHO-DD]
Common Name English
GRAZOPREVIR [USAN]
Common Name English
MK-5172 MONOHYDRATE
Code English
CYCLOPROPANECARBOXAMIDE, N-((((1R,2R)-2-(5-(3-HYDROXY-6-METHOXY-2-QUINOXALINYL)PENTYL)CYCLOPROPYL)OXY)CARBONYL)-3-METHYL-L-VALYL-(4R)-4-HYDROXY-L-PROLYL-1-AMINO-N-(CYCLOPROPYLSULFONYL)-2-ETHENYL-, CYCLIC (1->2)-ETHER, HYDRATE (1:1), (1R,2S)-
Systematic Name English
GRAZOPREVIR HYDRATE [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC J05AP54
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
Code System Code Type Description
DRUG CENTRAL
5081
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
CAS
1350462-55-3
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
ChEMBL
CHEMBL2063090
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
LACTMED
Grazoprevir
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
EPA CompTox
1350462-55-3
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
WIKIPEDIA
Grazoprevir
Created by admin on Sat Jun 26 03:44:19 UTC 2021 , Edited by admin on Sat Jun 26 03:44:19 UTC 2021
PRIMARY
NCI_THESAURUS
C166768
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
FDA UNII
4O2AB118LA
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
EVMPD
SUB180368
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
RXCUI
1734630
Created by admin on Sat Jun 26 03:44:19 UTC 2021 , Edited by admin on Sat Jun 26 03:44:19 UTC 2021
PRIMARY
DRUG BANK
DB11575
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
PUBCHEM
71576667
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
MERCK INDEX
M11947
Created by admin on Sat Jun 26 03:44:18 UTC 2021 , Edited by admin on Sat Jun 26 03:44:18 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY