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Details

Stereochemistry ABSOLUTE
Molecular Formula C38H50N6O9S
Molecular Weight 766.903
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GRAZOPREVIR ANHYDROUS

SMILES

COC1=CC2=NC3=C(CCCCC[C@@H]4C[C@H]4OC(=O)N[C@H](C(=O)N5C[C@@H](C[C@H]5C(=O)N[C@@]6(C[C@H]6C=C)C(=O)NS(=O)(=O)C7CC7)O3)C(C)(C)C)N=C2C=C1

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

Description

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.

CNS Activity

Originator

Approval Year

Target Info

Target Info

Primary TargetPharmacologyConditionPotency
0.02 nM [Ki]
Condition Info

Condition Info

ConditionModalityTargetsHighest PhaseProduct
Primary
ZEPATIER
PMID

PMID

TitleDatePMID
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 for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study.
2017 Sep
Elbasvir/Grazoprevir Use in Postliver Transplantation Patients on Hemodialysis.
2017 Sep
Patent

Sample Use Guides

In Vivo Use Guide
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 Vitro Use Guide
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.
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
Code System Code Type Description
CAS
1350514-68-9
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY
NDF-RT
N0000190114
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
INN
9857
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY
EVMPD
SUB174126
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY
CAS
1206524-75-5
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
SUPERSEDED
RXCUI
1871173
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY
CAS
1356446-42-8
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
SUPERSEDED
NDF-RT
N0000182638
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY HCV NS3/4A Protease Inhibitors [MoA]
EPA CompTox
1350514-68-9
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY
PUBCHEM
44603531
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY SWITZERF
NDF-RT
N0000190113
Created by admin on Tue Mar 06 11:10:32 UTC 2018 , Edited by admin on Tue Mar 06 11:10:32 UTC 2018
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]