Vaniprevir

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 326810

CAS#: 923590-37-8

Description: Vaniprevir, also known as MK7009, is a macrocyclic hepatitis C virus (HCV) NS3/4a protease inhibitor. Vaniprevir is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes and has good plasma exposure and excellent liver exposure in multiple species. Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for QD or BID administration. In Japan, it was approved for treating hepatitis C in 2014.


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Vaniprevir is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 326810
Name: Vaniprevir
CAS#: 923590-37-8
Chemical Formula: C38H55N5O9S
Exact Mass: 757.372
Molecular Weight: 757.944
Elemental Analysis: C, 60.22; H, 7.31; N, 9.24; O, 19.00; S, 4.23


Synonym: MK7009; MK-7009; MK 7009; Vaniprevir

IUPAC/Chemical Name: Cyclopropanecarboxamide, N-(((6-(2-carboxy-2,3-dihydro-1H-isoindol-4-yl)-2,2-dimethylhexyl)oxy)carbonyl)-3-methyl-L-valyl-(4R)-4-hydroxy-L-prolyl-1-amino-N-(cyclopropylsulfonyl)-2-ethyl-, (1-2)-lactone, (1R,2R)-

InChi Key: KUQWGLQLLVFLSM-ONAXAZCASA-N

InChi Code: InChI=1S/C38H55N5O9S/c1-7-25-18-38(25,33(46)41-53(49,50)27-14-15-27)40-31(44)29-17-26-20-43(29)32(45)30(36(2,3)4)39-34(47)51-22-37(5,6)16-9-8-11-23-12-10-13-24-19-42(21-28(23)24)35(48)52-26/h10,12-13,25-27,29-30H,7-9,11,14-22H2,1-6H3,(H,39,47)(H,40,44)(H,41,46)/t25-,26-,29+,30-,38-/m1/s1

SMILES Code: CC[C@@H]1C[C@@]1(C(NS(=O)(C2CC2)=O)=O)NC([C@@H]3C[C@@H]4CN3C([C@H](C(C)(C)C)NC(OCC(C)(CCCCC5=CC=CC6=C5CN(C(O4)=O)C6)C)=O)=O)=O


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Ludmerer SW, Hirano T, Black S, Howe AY, Chang W, Takase A, Nakamura K, Tanaka Y, Kumada H, Hayashi N, Nickle D. HCV evolutionary genetics of SVR versus virologic failure assessed from the vaniprevir phase III registration trials. Antiviral Res. 2016 Jun;130:118-29. doi: 10.1016/j.antiviral.2016.03.004. Epub 2016 Mar 3. PubMed PMID: 26947564.

2: Kumada H, Mochida S, Suzuki F, Chayama K, Karino Y, Nakamura K, Fujimoto G, Howe AY, Ludmerer SW, Mobashery N. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 (GT1b) infection: phase 3 studies. J Gastroenterol Hepatol. 2016 Mar 2. doi: 10.1111/jgh.13328. [Epub ahead of print] PubMed PMID: 26936417.

3: Takehara T. [Vaniprevir with pegylated interferon and ribavirin in treatment for chronic hepatitis C]. Nihon Rinsho. 2015 Dec;73 Suppl 9:254-6. Japanese. PubMed PMID: 26845940.

4: Uchida T, Hiraga N, Imamura M, Yoshimi S, Kan H, Miyaki E, Tsuge M, Abe H, Hayes CN, Aikata H, Ishida Y, Tateno C, Ellis JD, Chayama K. Elimination of HCV via a non-ISG-mediated mechanism by vaniprevir and BMS-788329 combination therapy in human hepatocyte chimeric mice. Virus Res. 2016 Feb 2;213:62-8. doi: 10.1016/j.virusres.2015.11.010. Epub 2015 Nov 10. PubMed PMID: 26569595.

5: Hayashi N, Nakamuta M, Takehara T, Kumada H, Takase A, Howe AY, Ludmerer SW, Mobashery N. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-naive Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase III study. J Gastroenterol. 2016 Apr;51(4):390-403. doi: 10.1007/s00535-015-1120-x. Epub 2015 Sep 25. PubMed PMID: 26403160; PubMed Central PMCID: PMC4805724.

6: Kinoshita K, Iwasa T, Takase A, Nakamura K. [Preclinical and clinical properties of vaniprevir (VANIHEP® Capsules 150 mg), a novel therapeutic agent for hepatitis C]. Nihon Yakurigaku Zasshi. 2015 Sep;146(3):159-70. doi: 10.1254/fpj.146.159. Review. Japanese. PubMed PMID: 26354016.

7: Wright DH, Caro L, Cerra M, Panorchan P, Du L, Anderson M, Potthoff A, Nachbar RB, Wagner J, Manns MP, Talal AH. Liver-to-plasma vaniprevir (MK-7009) concentration ratios in HCV-infected patients. Antivir Ther. 2015;20(8):843-8. doi: 10.3851/IMP2958. Epub 2015 Apr 7. PubMed PMID: 25849338; PubMed Central PMCID: PMC4714953.

8: Hayashi N, Mobashery N, Izumi N. Vaniprevir plus peginterferon alfa-2a and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase II study. J Gastroenterol. 2015 Feb;50(2):238-48. doi: 10.1007/s00535-014-0979-2. Epub 2014 Aug 13. PubMed PMID: 25115901; PubMed Central PMCID: PMC4318982.

9: Takayama K, Furusyo N, Ogawa E, Shimizu M, Hiramine S, Mitsumoto F, Ura K, Toyoda K, Murata M, Hayashi J. A case of successful treatment with telaprevir-based triple therapy for hepatitis C infection after treatment failure with vaniprevir-based triple therapy. J Infect Chemother. 2014 Sep;20(9):577-81. doi: 10.1016/j.jiac.2014.06.002. Epub 2014 Jul 4. PubMed PMID: 25000830.

10: Rodriguez-Torres M, Stoehr A, Gane EJ, Serfaty L, Lawitz E, Zhou A, Bourque M, Bhanja S, Strizki J, Barnard RJ, Hwang PM, DiNubile MJ, Mobashery N. Combination of vaniprevir with peginterferon and ribavirin significantly increases the rate of SVR in treatment-experienced patients with chronic HCV genotype 1 infection and cirrhosis. Clin Gastroenterol Hepatol. 2014 Jun;12(6):1029-37.e5. doi: 10.1016/j.cgh.2013.09.067. Epub 2013 Oct 10. PubMed PMID: 24120953.

11: Barnard RJ, McHale CM, Newhard W, Cheney CA, Graham DJ, Himmelberger AL, Strizki J, Hwang PM, Rivera AA, Reeves JD, Nickle D, Dinubile MJ, Hazuda DJ, Mobashery N. Emergence of resistance-associated variants after failed triple therapy with vaniprevir in treatment-experienced non-cirrhotic patients with hepatitis C-genotype 1 infection: a population and clonal analysis. Virology. 2013 Sep 1;443(2):278-84. doi: 10.1016/j.virol.2013.05.013. Epub 2013 Jun 10. PubMed PMID: 23763767.

12: Lawitz E, Sulkowski M, Jacobson I, Kraft WK, Maliakkal B, Al-Ibrahim M, Gordon SC, Kwo P, Rockstroh JK, Panorchan P, Miller M, Caro L, Barnard R, Hwang PM, Gress J, Quirk E, Mobashery N. Characterization of vaniprevir, a hepatitis C virus NS3/4A protease inhibitor, in patients with HCV genotype 1 infection: safety, antiviral activity, resistance, and pharmacokinetics. Antiviral Res. 2013 Sep;99(3):214-20. doi: 10.1016/j.antiviral.2013.05.015. Epub 2013 Jun 7. PubMed PMID: 23747481.

13: Xue W, Ban Y, Liu H, Yao X. Computational study on the drug resistance mechanism against HCV NS3/4A protease inhibitors vaniprevir and MK-5172 by the combination use of molecular dynamics simulation, residue interaction network, and substrate envelope analysis. J Chem Inf Model. 2014 Feb 24;54(2):621-33. doi: 10.1021/ci400060j. Epub 2013 Jun 28. PubMed PMID: 23745769.

14: Lawitz E, Rodriguez-Torres M, Stoehr A, Gane EJ, Serfaty L, Bhanja S, Barnard RJ, An D, Gress J, Hwang P, Mobashery N. A phase 2B study of MK-7009 (vaniprevir) in patients with genotype 1 HCV infection who have failed previous pegylated interferon and ribavirin treatment. J Hepatol. 2013 Jul;59(1):11-7. doi: 10.1016/j.jhep.2013.02.008. Epub 2013 Feb 21. PubMed PMID: 23439259.

15: Manns MP, Gane E, Rodriguez-Torres M, Stoehr A, Yeh CT, Marcellin P, Wiedmann RT, Hwang PM, Caro L, Barnard RJ, Lee AW; MK-7009 Protocol 007 Study Group. Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: a randomized phase II study. Hepatology. 2012 Sep;56(3):884-93. doi: 10.1002/hep.25743. Epub 2012 Jul 17. PubMed PMID: 22473713.

16: Kong J, Chen CY, Balsells-Padros J, Cao Y, Dunn RF, Dolman SJ, Janey J, Li H, Zacuto MJ. Synthesis of the HCV protease inhibitor Vaniprevir (MK-7009) using ring-closing metathesis strategy. J Org Chem. 2012 Apr 20;77(8):3820-8. doi: 10.1021/jo3001595. Epub 2012 Apr 10. PubMed PMID: 22458448.

17: Song ZJ, Tellers DM, Journet M, Kuethe JT, Lieberman D, Humphrey G, Zhang F, Peng Z, Waters MS, Zewge D, Nolting A, Zhao D, Reamer RA, Dormer PG, Belyk KM, Davies IW, Devine PN, Tschaen DM. Synthesis of vaniprevir (MK-7009): lactamization to prepare a 20-membered [corrected] macrocycle. J Org Chem. 2011 Oct 7;76(19):7804-15. doi: 10.1021/jo2011494. Epub 2011 Aug 31. Erratum in: J Org Chem. 2011 Nov 18;76(22):9553. PubMed PMID: 21838271.

18: McCauley JA, McIntyre CJ, Rudd MT, Nguyen KT, Romano JJ, Butcher JW, Gilbert KF, Bush KJ, Holloway MK, Swestock J, Wan BL, Carroll SS, DiMuzio JM, Graham DJ, Ludmerer SW, Mao SS, Stahlhut MW, Fandozzi CM, Trainor N, Olsen DB, Vacca JP, Liverton NJ. Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor. J Med Chem. 2010 Mar 25;53(6):2443-63. doi: 10.1021/jm9015526. PubMed PMID: 20163176.