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Details

Stereochemistry ABSOLUTE
Molecular Formula C38H50N6O9S
Molecular Weight 766.906
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GRAZOPREVIR ANHYDROUS

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

InChI

InChIKey=OBMNJSNZOWALQB-NCQNOWPTSA-N
InChI=1S/C38H50N6O9S/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)/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

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 06:54:15 UTC 2021
Edited
by admin
on Sat Jun 26 06:54:15 UTC 2021
Record UNII
8YE81R1X1J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GRAZOPREVIR ANHYDROUS
Common Name English
MK-5172
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, (1R,2S)-
Systematic Name English
MK-5172 ANHYDROUS
Code English
GRAZOPREVIR COMPONENT OF ZEPATIER
Common Name English
GRAZOPREVIR [WHO-DD]
Common Name English
ZEPATIER COMPONENT OF GRAZOPREVIR
Common Name English
GRAZOPREVIR [INN]
Common Name English
GRAZOPREVIR [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000182639
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
Code System Code Type Description
CAS
1350514-68-9
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
NDF-RT
N0000190114
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
INN
9857
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
MERCK INDEX
M11947
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
FDA UNII
8YE81R1X1J
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
EVMPD
SUB174126
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
CAS
1206524-75-5
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
SUPERSEDED
NCI_THESAURUS
C175724
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
RXCUI
1871173
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
CAS
1356446-42-8
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
SUPERSEDED
NDF-RT
N0000182638
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY HCV NS3/4A Protease Inhibitors [MoA]
EPA CompTox
1350514-68-9
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
PUBCHEM
44603531
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY
NDF-RT
N0000190113
Created by admin on Sat Jun 26 06:54:15 UTC 2021 , Edited by admin on Sat Jun 26 06:54:15 UTC 2021
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION