Paritaprevir

• CAT Number: I000824
• CAS Number: 1216941-48-8
• Molecular Formula: C40H43N7O7S
• Molecular Weight: 765.88
• Purity: ≥95%
• Target: NS3-4A serine protease
• Solubility: 10 mM in DMSO
• Storage: Store at +4C
• IC50: 0.09 to 19 nM (EC50, for HCV GT 1-4), 0.09 nM (EC50, for GT 4a) [1]
• IUPAC Name: (1S,4R,6S,7Z,14S,18R)-N-cyclopropylsulfonyl-14-[(5-methylpyrazine-2-carbonyl)amino]-2,15-dioxo-18-phenanthridin-6-yloxy-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxamide
• InChI: InChI=1S/C40H43N7O7S/c1-24-21-42-33(22-41-24)35(48)43-32-16-6-4-2-3-5-11-25-20-40(25,39(51)46-55(52,53)27-17-18-27)45-36(49)34-19-26(23-47(34)38(32)50)54-37-30-14-8-7-12-28(30)29-13-9-10-15-31(29)44-37/h5,7-15,21-22,25-27,32,34H,2-4,6,16-20,23H2,1H3,(H,43
• InChIKey: UAUIUKWPKRJZJV-QPLHLKROSA-N
• SMILES: O=C([C@]([C@]1([H])/C=CCCCCC[C@@H]2NC(C3=NC=C(C)N=C3)=O)(C1)NC([C@@](C[C@@H](OC4=C5C=CC=CC5=C(C=CC=C6)C6=N4)C7)([H])N7C2=O)=O)NS(=O)(C8CC8)=O

Paritaprevir (CAS 1216941-48-8) is an acylsulfonamide inhibitor of the NS3-4A serine protease that shows promising results as a treatment of hepatitis C. Paritaprevir is an NS3/4A inhibitor that is coadministered with the pharmacokinetic enhancer ritonavir (paritaprevir/r) to increase the plasma concentration and half-life of paritaprevir. Paritaprevir demonstrated in vitro antiviral activity against HCV GT 1-4 and 6 (EC50 value range of 0.09 to 19 nM), with an EC50 value of 0.09 nM against GT 4a.

Reference

1:Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study. Petta S, Marzioni M, Russo P, Aghemo A, Alberti A, Ascione A, Antinori A, Bruno R, Bruno S, Chirianni A, Gaeta GB, Giannini EG, Merli M, Messina V, Montilla S, Perno CF, Puoti M, Raimondo G, Rendina M, Silberstein FC, Villa E, Zignego AL, Pani L, Craxì A; ABACUS study group.; AIFA team..Lancet Gastroenterol Hepatol. 2017 Jun;2(6):427-434. doi: 10.1016/S2468-1253(17)30048-1. Epub 2017 Apr 10. PMID: 28497758
2:Mechanisms and Predictions of Drug-Drug Interactions of the Hepatitis C Virus 3-Direct Acting Antiviral (3D) Regimen: Paritaprevir/Ritonavir, Ombitasvir and Dasabuvir. Shebley M, Liu J, Kavetskaia O, Sydor J, de Morais SM, Fischer V, Nijsen MJ, Bow DA.Drug Metab Dispos. 2017 May 8. pii: dmd.116.074518. doi: 10.1124/dmd.116.074518. [Epub ahead of print] PMID: 28483778
3:Real-World Effectiveness of Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir ± Ribavirin in Patients with HCV Genotype 1 or 4 Infection: a Meta-Analysis. Wedemeyer H, Craxí A, Zuckerman E, Dieterich D, Flisiak R, Roberts SK, Pangerl A, Zhang Z, Martinez M, Bao Y, Calleja JL.J Viral Hepat. 2017 May 8. doi: 10.1111/jvh.12722. [Epub ahead of print] PMID: 28480525
4:Efficacy and safety of ombitasvir/paritaprevir/ritonavir in dialysis patients with genotype 1b chronic hepatitis C. Atsukawa M, Tsubota A, Koushima Y, Ikegami T, Watanabe K, Shimada N, Sato S, Kato K, Abe H, Okubo T, Arai T, Itokawa N, Kondo C, Mikami S, Asano T, Chuganji Y, Matsuzaki Y, Iwakiri K.Hepatol Res. 2017 Apr 29. doi: 10.1111/hepr.12910. [Epub ahead of print] PMID: 28457003
5:Real-world efficacy and safety of ritonavir-boosted paritaprevir, ombitasvir, dasabuvir ± ribavirin for hepatitis C genotype 1 – final results of the REV1TAL study. Lubel J, Strasser S, Stuart KA, Dore G, Thompson A, Pianko S, Bollipo S, Mitchell JL, Fragomeli V, Jones T, Chivers S, Gow P, Iser D, Levy M, Tse E, Gazzola A, Cheng W, Nazareth S, Galhenage S, Wade A, Weltman M, Wigg A, MacQuillan G, Sasadeusz J, George J, Zekry A, Roberts SK; Australian Liver Association Clinical Research Network (ALA CRN)..Antivir Ther. 2017 Apr 19. doi: 10.3851/IMP3168. [Epub ahead of print] PMID: 28422043
6:Ombitasvir, paritaprevir, and ritonavir plus dasabuvir for 8 weeks in previously untreated patients with hepatitis C virus genotype 1b infection without cirrhosis (GARNET): a single-arm, open-label, phase 3b trial. Welzel TM, Asselah T, Dumas EO, Zeuzem S, Shaw D, Hazzan R, Forns X, Pilot-Matias T, Lu W, Cohen DE, Feld JJ.Lancet Gastroenterol Hepatol. 2017 Apr 13. pii: S2468-1253(17)30071-7. doi: 10.1016/S2468-1253(17)30071-7. [Epub ahead of print] PMID: 28416221
7:Drug Induced Pneumonitis Secondary to Treatment with Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir (VIEKIRA PAK®) for Chronic Hepatitis C: Case Report of an Unexpected Life-Threatening Adverse Reaction. Wu SY, Faire B, Gane E.Case Rep Med. 2017;2017:4895736. doi: 10.1155/2017/4895736. Epub 2017 Mar 20. PMID: 28408931 Free PMC Article
8:Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial. Waked I, Shiha G, Qaqish RB, Esmat G, Yosry A, Hassany M, Soliman R, Mohey MA, Allam N, Zayed N, Asselah T, Hall C, Redman R, Mobashery N, Doss W.Lancet Gastroenterol Hepatol. 2016 Sep;1(1):36-44. doi: 10.1016/S2468-1253(16)30002-4. Epub 2016 Jun 16. PMID: 28404110
9:Ombitasvir, paritaprevir, and ritonavir plus ribavirin in adults with hepatitis C virus genotype 4 infection and cirrhosis (AGATE-I): a multicentre, phase 3, randomised open-label trial. Asselah T, Hézode C, Qaqish RB, ElKhashab M, Hassanein T, Papatheodoridis G, Feld JJ, Moreno C, Zeuzem S, Ferenci P, Yu Y, Redman R, Pilot-Matias T, Mobashery N.Lancet Gastroenterol Hepatol. 2016 Sep;1(1):25-35. doi: 10.1016/S2468-1253(16)30001-2. Epub 2016 Jun 16. PMID: 28404108
10:Real-World Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir/+Dasabuvir±Ribavirin (OBV/PTV/r/+DSV±RBV) Therapy in Recurrent Hepatitis C Virus (HCV) Genotype 1 Infection Post-Liver Transplant: AMBER-CEE Study. Tronina O, Durlik M, Wawrzynowicz-Syczewska M, Buivydiene A, Katzarov K, Kupcinskas L, Tolmane I, Karpińska E, Pisula A, Karwowska KM, Bolewska B, Jabłkowski M, Rostkowska K, Jakutiene J, Simonova M, Flisiak R.Ann Transplant. 2017 Apr 7;22:199-207. PMID: 28386057 Free Article