Grazoprevir

Grazoprevir
Clinical data

Routes of administration	Oral
Legal status
Legal status	Investigational
Identifiers
IUPAC name (1R,18R,20R,24S,27S)-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-vinylcyclopropyl}-7-methoxy-24-(2-methyl-2-propanyl)-22,25-dioxo-2,21-dioxa-4,11,23,26-tetraazapentacyclo[24.2.1.03,12.05,10.0 18,20]nonacosa-3,5,7,9,11-pentaene-27-carboxamide
CAS Number	1350514-68-9
PubChem (CID)	44603531
ChemSpider	28506694
ChEBI	CHEBI:132975^Y
Chemical and physical data
Formula	C₃₈H₅₀N₆O₉S
Molar mass	766.901 g/mol
3D model (Jmol)	Interactive image
SMILES O=C1C(C(C)(C)C)NC(=O)OC3CC3CCCCCc2nc4ccc(OC)cc4nc2OC(C6)CN1C6C(=O)NC5(CC5C=C)C(=O)NS(=O)(=O)C7CC7

Grazoprevir (MK-5172) is a drug ^[1]approved for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, following promising results in Phase II when used in combination with the NS5A replication complex inhibitor elbasvir, either with or without ribavirin.^[2]

Grazoprevir is a second generation hepatitis C virus protease inhibitor acting at the NS3/4a protease targets.^[3] It has good activity against a range of HCV genotype variants, including some that are resistant to most currently used antiviral medications.^[4]^[5]

References

↑ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483828.htm
↑ Lawitz E, Gane E, Pearlman B, Tam E, Ghesquiere W, Guyader D, Alric L, Bronowicki JP, Lester L, Sievert W, Ghalib R, Balart L, Sund F, Lagging M, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015;385(9973):1075-86. doi: 10.1016/S0140-6736(14)61795-5. PMID 25467591
↑ Harper S, McCauley JA, Rudd MT, Ferrara M, DiFilippo M, Crescenzi B, Koch U, Petrocchi A, Holloway MK, Butcher JW, Romano JJ, Bush KJ, Gilbert KF, McIntyre CJ, Nguyen KT, Nizi E, Carroll SS, Ludmerer SW, Burlein C, DiMuzio JM, Graham DJ, McHale CM, Stahlhut MW, Olsen DB, Monteagudo E, Cianetti S, Giuliano C, Pucci V, Trainor N, Fandozzi CM, Rowley M, Coleman PJ, Vacca JP, Summa V, Liverton NJ. Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACS Med Chem Lett. 2012;3(4):332-6. doi: 10.1021/ml300017p. PMID 24900473
↑ Summa V, Ludmerer SW, McCauley JA, Fandozzi C, Burlein C, Claudio G, Coleman PJ, Dimuzio JM, Ferrara M, Di Filippo M, Gates AT, Graham DJ, Harper S, Hazuda DJ, Huang Q, McHale C, Monteagudo E, Pucci V, Rowley M, Rudd MT, Soriano A, Stahlhut MW, Vacca JP, Olsen DB, Liverton NJ, Carroll SS. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother. 2012;56(8):4161-7. doi: 10.1128/AAC.00324-12. PMID 22615282
↑ Gentile I, Buonomo AR, Borgia F, Zappulo E, Castaldo G, Borgia G. MK-5172 : a second-generation protease inhibitor for the treatment of hepatitis C virus infection. Expert Opinion on Investigational Drugs. 2014;23(5):719-28. doi: 10.1517/13543784.2014.902049. PMID 24666106

RNA virus antivirals (primarily J05, also S01AD and D06BB)

Hepatitis C

NS3/4A protease inhibitors (–previr)	Asunaprevir Boceprevir Faldaprevir^‡ Grazoprevir Paritaprevir Simeprevir Telaprevir

NS5A inhibitors (–asvir)	Daclatasvir Elbasvir Ledipasvir MK-3682 MK-8408 Odalasvir^† Ombitasvir Ravidasvir^† Samatasvir^† Velpatasvir

NS5B RNA polymerase inhibitors (–buvir)	Beclabuvir^† Dasabuvir Deleobuvir^§ Filibuvir^§ Setrobuvir^§ Sofosbuvir Radalbuvir^†

Combination drugs	Elbasvir/grazoprevir Ledipasvir/sofosbuvir Ombitasvir/paritaprevir/ritonavir Sofosbuvir/daclatasvir Velpatasvir/sofosbuvir

Picornavirus

viral entry: Pleconaril^†

Anti-influenza agents

Umifenovir

neuraminidase inhibitors/release phase (Oseltamivir
Zanamivir
Peramivir, Laninamivir^†)

Multiple/general

Interferon	Interferon alfa 2b Peginterferon alfa-2a^#

Multiple/unknown	BCX4430^† Favipiravir GS-5734^† Mericitabine^† MK-608^§ NITD008^§ Moroxydine Ribavirin^#/Taribavirin^† Triazavirin

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

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