MK-5172

Category	HCV Protease
CAS	1350514-68-9
Description	Grazoprevir is a hepatitis C virus protease inhibitor developed for the treatment of hepatitis C. It suppresses NS3 and NS4A, which play a role in the virus splitting its polyprotein into the functional virus proteins. Grazoprevir is often used in combination with elbasvir or ribavirin.

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Product Information

Synonyms	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)-; Grazoprevir; (1R,2S)-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-ethenylcyclopropanecarboxamide Cyclic (1→2)-Ether
IUPAC Name	(1R,18R,20R,24S,27S)-24-tert-butyl-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-7-methoxy-22,25-dioxo-2,21-dioxa-4,11,23,26-tetrazapentacyclo[24.2.1.03,12.05,10.018,20]nonacosa-3,5(10),6,8,11-pentaene-27-carboxamide
Molecular Weight	766.91
Molecular Formula	C38H50N6O9S
Canonical SMILES	CC(C)(C)C1C(=O)N2CC(CC2C(=O)NC3(CC3C=C)C(=O)NS(=O)(=O)C4CC4)OC5=NC6=C(C=CC(=C6)OC)N=C5CCCCCC7CC7OC(=O)N1
InChI	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
InChIKey	OBMNJSNZOWALQB-NCQNOWPTSA-N
Boiling Point	825.0±65.0 °C at 760 mmHg
Melting Point	180-185°C
Flash Point	452.7±34.3 °C
Purity	>98%
Density	1.38±0.1 g/cm3
Solubility	Soluble in Acetone (Slightly), Chloroform (Slightly), DMSO (Slightly, Sonicated), Methanol
Appearance	White to Off-white Solid
Application	Antiviral Agents
Storage	Store at -20°C
Animal Admin	In biochemical analysis, Grazoprevir (MK-5172) was effective against a group of major genotypes and variants with common resistance mutations with a Ki of 0.01±<0.01 nM (gt1b), 0.01±0.01 nM (gt1a), 0.08±0.02 nM (gt2a), 0.15±0.06nM (gt2b), 0.90±0.2nM (gt3a), and 0.07 ± 0.01nM(gt1bR155K), 0.14±0.03nM(gt1bD168V), 0.30±0.04nM (gt1bD168Y), 5.3±0.9nM (gt1bA156T) 12±2nM(gt1bA156V), respectively. In the replicon assay, Grazoprevir showed subnanomolar to low nanomolar EC50 for genotypes 1a, 1b, and 2a, and EC50s of 0.5±0.1nM, 2±1nM, and 2±1nM, respectively, for gt1bcon1, gt1a, and gt2a. Grazoprevir is valid against a group of HCV replication mutants NS5A (Y93H) (EC50 = 0.7±0.3 nM), NS5B nucleoside (S282T) (EC50 = 0.3±0.1 nM), and NS5B (C316Y) (EC50 = 0.4±0.2). Grazoprevir (MK-5172) maintains excellent potency against gt 3a enzyme as well as a broad group of mutant enzymes, with excellent potency in replicons [gt1b IC50 (50% NHS) = 7.4 nM; gtaa IC50 (40% NHS) = 7 nM], showing excellent rat liver exposure.
Complexity	1580
Exact Mass	766.33599837
Index Of Refraction	1.616
In Vitro	In biochemical analysis, Grazoprevir (MK-5172) was effective against a group of major genotypes and variants with common resistance mutations with a Ki of 0.01±<0.01 nM (gt1b), 0.01±0.01 nM (gt1a), 0.08±0.02 nM (gt2a), 0.15±0.06nM (gt2b), 0.90±0.2nM (gt3a), and 0.07 ± 0.01nM(gt1bR155K), 0.14±0.03nM(gt1bD168V), 0.30±0.04nM (gt1bD168Y), 5.3±0.9nM (gt1bA156T) 12±2nM(gt1bA156V), respectively. In the replicon assay, Grazoprevir showed subnanomolar to low nanomolar EC50 for genotypes 1a, 1b, and 2a, and EC50s of 0.5±0.1nM, 2±1nM, and 2±1nM, respectively, for gt1bcon1, gt1a, and gt2a. Grazoprevir is valid against a group of HCV replication mutants NS5A (Y93H) (EC50 = 0.7±0.3 nM), NS5B nucleoside (S282T) (EC50 = 0.3±0.1 nM), and NS5B (C316Y) (EC50 = 0.4±0.2). Grazoprevir (MK-5172) maintains excellent potency against gt 3a enzyme as well as a broad group of mutant enzymes, with excellent potency in replicons [gt1b IC50 (50% NHS) = 7.4 nM; gtaa IC50 (40% NHS) = 7 nM], showing excellent rat liver exposure.
In Vivo	Grazoprevir (MK-5172) is effective in vivo against chronically HCV-infected chimpanzees. When administered to dogs, Grazoprevir (MK-5172) showed a low clearance of 5 mL / min / kg after intravenous administration and a half-life of 3 h with good plasma exposure (AUC = 0.4 μMh) dose after 1 mg / kg oral dose. Dog liver biopsy studies have shown that the liver concentration of Grazoprevir after 1 mg/kg oral dose is 1.4 μM at a 24 h time point. Similar to its behavior in rats, Grazoprevir demonstrates effective distribution into liver tissue and maintains high liver concentrations relative to potency for 24 h after oral administration in dogs.
PSA	143.67000
Target	HCV Protease; HCV; SARS-CoV
Vapor Pressure	0.0±3.1 mmHg at 25°C
XLogP3-AA	4.7