grazoprevir

{{Short description|Drug approved for the treatment of hepatitis C}}

{{Drugbox

| 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[24.2.1.0^3,12.0^5,10.0 18,20]nonacosa-3,5,7,9,11-pentaene-27-carboxamide

| image = Grazoprevir.svg

| tradename = Zepatier (combination with elbasvir)

| Drugs.com =

| MedlinePlus =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| licence_EU = yes

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US = Rx-only

| legal_status =

| routes_of_administration = Oral

| bioavailability =

| protein_bound = 98.8%

| metabolism = CYP3A4

| elimination_half-life = 31 hours

| excretion = >90% via faeces, <1% via urine

| CAS_number = 1350514-68-9

| ATCvet =

| ATC_prefix = J05

| ATC_suffix = AP11

| ATC_supplemental =
{{ATC|J05|AP54}} (combination with elbasvir)

| PubChem = 44603531

| DrugBank = DB11575

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 132975

| ChemSpiderID = 28506694

| KEGG = D10639

| UNII = 8YE81R1X1J

| synonyms = MK-5172

| C=38 | H=50 | N=6 | O=9 | S=1

| smiles = O=C1C(C(C)(C)C)NC(=O)OC3CC3CCCCCc2nc4ccc(OC)cc4nc2OC(C6)CN1C6C(=O)NC5(CC5C=C)C(=O)NS(=O)(=O)C7CC7

| StdInChI=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

| StdInChIKey = OBMNJSNZOWALQB-NCQNOWPTSA-N

| Jmol=None

}}

Grazoprevir is a drug{{Cite web | url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483828.htm |title = FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4| website=Food and Drug Administration |date = 2018-11-03}} approved for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, used in combination with the NS5A replication complex inhibitor elbasvir under the trade name Zepatier, either with or without ribavirin.{{cite journal | vauthors = 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 | display-authors = 6 | title = 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 | journal = Lancet | volume = 385 | issue = 9973 | pages = 1075–86 | date = March 2015 | pmid = 25467591 | doi = 10.1016/S0140-6736(14)61795-5 }}

Grazoprevir is a second generation hepatitis C virus protease inhibitor acting at the NS3/4A protease targets.{{cite journal | vauthors = 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 | display-authors = 6 | title = Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor | journal = ACS Medicinal Chemistry Letters | volume = 3 | issue = 4 | pages = 332–6 | date = April 2012 | pmid = 24900473 | pmc = 4025840 | doi = 10.1021/ml300017p }} It has good activity against a range of HCV genotype variants, including some that are resistant to most currently used antiviral medications.{{cite journal | vauthors = 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 | display-authors = 6 | title = MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants | journal = Antimicrobial Agents and Chemotherapy | volume = 56 | issue = 8 | pages = 4161–7 | date = August 2012 | pmid = 22615282 | pmc = 3421554 | doi = 10.1128/AAC.00324-12 }}{{cite journal | vauthors = Gentile I, Buonomo AR, Borgia F, Zappulo E, Castaldo G, Borgia G | title = MK-5172 : a second-generation protease inhibitor for the treatment of hepatitis C virus infection | journal = Expert Opinion on Investigational Drugs | volume = 23 | issue = 5 | pages = 719–28 | date = May 2014 | pmid = 24666106 | doi = 10.1517/13543784.2014.902049 | s2cid = 207477059 }}