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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

[H][C@@]12C[C@@]1([H])OC(=O)N[C@H](C(=O)N3C[C@@]([H])(C[C@H]3C(=O)N[C@@]4(C[C@@]4([H])C=C)C(=O)NS(=O)(=O)C5CC5)OC6=NC7=CC(OC)=CC=C7N=C6CCCCC2)C(C)(C)C

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 766.903
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Originator

Merck
231
Curator's Comment: # Merck

Approval Year

2016
483
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8146
 0.02 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8307
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

1.45393923E12
Sourcing

Sourcing

Vendor/AggregatorIDURL
AA Blocks
AA009CAJ
https://www.aablocks.com/goods/Goods/detail?id=AA009CAJ
Aaron Chemicals
AR009D2B
http://www.aaronchem.com/1350514-68-9
Achemtek
0102-013826
http://www.achemtek.com/1350514-68-9
Aurum Pharmatech LLC
W-6087
http://www.Aurumpharmatech.com/Product/ProductDetails/W_6087
BLD Pharm
BD293153
http://www.bldpharm.com/products/1350514-68-9.html
BioCrick
BCC1762
http://www.biocrick.com/MK-5172-BCC1762.html
Boerchem
BC600762
http://www.boerchem.com/?product_43596.html
CSNpharm
CSN13898
https://www.csnpharm.com/products/mk-5172.html
Chem Scene
CS-1374
http://www.chemscene.com/1350514-68-9.html
Chemspace
CSSB00161189429
https://chem-space.com/CSSB00161189429
Excenen
EX-A2253
https://www.excenen.com/searchresultlist.php?id=1350514-68-9
Lab Network
LN01342722
https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342722
MedChem Express
HY-15298
https://www.medchemexpress.com/MK-5172.html
MuseChem
I001345
https://www.musechem.com/product/I001345.html
Selleck Chemicals
S3728
http://www.selleckchem.com/products/grazoprevir.html
Smolecule
S548927
http://www.smolecule.com/products/s548927
Synblock Inc
SB16740
http://www.synblock.com/product/1350514-68-9.html
THE BioTek
bt-288332
https://www.thebiotek.com/product/inhibitors/bt-288332
eNovation Chemicals
D521399
https://www.enovationchem.com/ProductDetails.asp?ProductID=D521399
iChemical
EBD3315156
http://www.ichemical.com/products/1350514-68-9.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
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

Patents

US7973040
2
US8871759
2

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.
Substance Class Chemical
Created
by admin
on Sat Dec 17 23:58:23 UTC 2022
Edited
by admin
on Sat Dec 17 23:58:23 UTC 2022
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
ZEPATIER COMPONENT OF GRAZOPREVIR
Common Name English
Grazoprevir [WHO-DD]
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 Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
Code System Code Type Description
CAS
1350514-68-9
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
NDF-RT
N0000190114
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
INN
9857
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
MERCK INDEX
M11947
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
FDA UNII
8YE81R1X1J
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
EVMPD
SUB174126
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
CAS
1206524-75-5
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
SUPERSEDED
NCI_THESAURUS
C175724
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
RXCUI
1871173
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
CAS
1356446-42-8
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
SUPERSEDED
NDF-RT
N0000182638
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY HCV NS3/4A Protease Inhibitors [MoA]
EPA CompTox
DTXSID50159234
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
PUBCHEM
44603531
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
DAILYMED
8YE81R1X1J
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY
NDF-RT
N0000190113
Created by admin on Sat Dec 17 23:58:23 UTC 2022 , Edited by admin on Sat Dec 17 23:58:23 UTC 2022
PRIMARY Breast Cancer Resistance Protein Inhibitors [MoA]
Related Record Type Details
HCV NS3-4A SERINE PROTEASE
TARGET -> INHIBITOR
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
IC50
BSEP
TRANSPORTER -> INHIBITOR
IC50
ABCC-4
TRANSPORTER -> INHIBITOR
IC50
OATP-8
TRANSPORTER -> INHIBITOR
IC50
OATP-8
TRANSPORTER -> SUBSTRATE
OATP1B1
TRANSPORTER -> INHIBITOR
IC50
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2C8
METABOLIC ENZYME -> INHIBITOR
IC50
Structure of GRAZOPREVIR
SOLVATE->ANHYDROUS
MRP-3
TRANSPORTER -> SUBSTRATE
IC50
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
IC50
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
OATP1B1
TRANSPORTER -> SUBSTRATE
Structure of GRAZOPREVIR
SALT/SOLVATE -> PARENT
MRP-2
TRANSPORTER -> INHIBITOR
IC50
Related Record Type Details
Structure of (33R,35S,91R,92R,5S)-5-(TERT-BUTYL)-17-METHOXY-4,7-DIOXO-2,8-DIOXA-6-AZA-1(2,3)-QUINOXALINA-3(3,1)-PYRROLIDINA-9(1,2)-CYCLOPROPANACYCLOTETRADECAPHANE-35-CARBOXAMIDE
METABOLITE -> PARENT
Structure of GRAZOPREVIR METABOLITE M-10
METABOLITE -> PARENT
MAJOR
FECAL
Related Record Type Details
Structure of GRAZOPREVIR ANHYDROUS
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

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