Elbasvir

Elbasvir

Systematic (IUPAC) name
Dimethyl N,N’-([(6S)-6H-indolo[1,2-c][1,3]benzoxazine-3,10-diyl]bis{1H-imidazole-5,2-diyl-(2S)-pyrrolidine-2,1-diyl[(2S)-1-oxo-3-methylbutane-1,2-diyl]})biscarbamate
Clinical data
Routes of administration	Oral
Legal status	Investigational
Identifiers
CAS Number	1370468-36-2
ChemSpider	30843797
Chemical data
Formula	C49H55N9O7
Molar mass	882.015 g/mol
SMILES CC(C)[C@@H](C(=O)N1CCC[C@H]1c2[nH]cc(n2)c3ccc4c(c3)cc-5n4[C@@H](Oc6c5ccc(c6)c7c[nH]c(n7)[C@@H]8CCCN8C(=O)[C@H](C(C)C)NC(=O)OC)c9ccccc9)NC(=O)OC
InChI InChI=1S/C49H55N9O7/c1-27(2)41(54-48(61)63-5)45(59)56-20-10-14-37(56)43-50-25-34(52-43)30-17-19-36-32(22-30)23-39-33-18-16-31(24-40(33)65-47(58(36)39)29-12-8-7-9-13-29)35-26-51-44(53-35)38-15-11-21-57(38)46(60)42(28(3)4)55-49(62)64-6/h7-9,12-13,16-19,22-28,37-38,41-42,47H,10-11,14-15,20-21H2,1-6H3,(H,50,52)(H,51,53)(H,54,61)(H,55,62)/t37-,38-,41-,42-,47-/m0/s1 Key:BVAZQCUMNICBAQ-PZHYSIFUSA-N

Elbasvir (MK-8742) is a drug approved^[1] 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 NS3/4a protease inhibitor grazoprevir, either with or without ribavirin.^[2]

Elbasvir is a highly potent and selective inhibitor of the hepatitis C virus NS5a replication complex.^[3] It has only been investigated as a combination product with other complementary hepatitis C antiviral drugs such as grazoprevir and MK-3682, and it is unclear whether elbasvir would show robust antiviral activity if it was administered by itself. Nevertheless, combination products of this type represent the most successful approach yet developed for actually curing hepatitis C, rather than merely slowing the progression of the disease.^[4]

References

1. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483828.htm
2. 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 (2015). "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 385 (9973): 1075–86. doi:10.1016/S0140-6736(14)61795-5. PMID 25467591.
3. Coburn, CA; Meinke, PT; Chang, W; Fandozzi, CM; Graham, DJ; Hu, B; Huang, Q; Kargman, S; Kozlowski, J; Liu, R; McCauley, JA; Nomeir, AA; Soll, RM; Vacca, JP; Wang, D; Wu, H; Zhong, B; Olsen, DB; Ludmerer, SW (2013). "Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity". ChemMedChem 8 (12): 1930–40. doi:10.1002/cmdc.201300343. PMID 24127258.
4. Gentile, I; Buonomo, AR; Zappulo, E; Borgia, G (Jul 2014). "Interferon-free therapies for chronic hepatitis C: toward a hepatitis C virus-free world?". Expert Review of Anti-Infective Therapy 12 (7): 763–73. doi:10.1586/14787210.2014.929497. PMID 24918116.