Name: Velpatasvir
CAS#: 1377049-84-7
Chemical Formula: C49H54N8O8
Exact Mass: 882.4065
Molecular Weight: 883.019
Elemental Analysis: C, 66.65; H, 6.16; N, 12.69; O, 14.49
EOS Med Chem produce Velpatasvir , 1377049-84-7, GS5816 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
Velpatasvir , 1377049-84-7, GS5816 Intermediates, EOS Med Chem have 8; Velpatasvir , 1377049-84-7, GS5816 Impurity we have 10, all from GMP, FDA plant.
Now Velpatasvir , 1377049-84-7, GS5816 DMF document is preparing.
Until 2016, Aug, Velpatasvir , 1377049-84-7, GS5816 more than produced 25kg API, 120kg Intermediates
Velpatasvir Intermediate (2S,4S)-4-(Methoxymethyl)-1,2-pyrrolidinedicarboxylic acid 1-(1,1-dimethylethyl) ester 1378388-16-9
Velpatasvir Intermediate (5S)-N-(Methoxycarbonyl)-L-valyl-5-methyl-L-proline 1335316-40-9
Velpatasvir Intermediate 3-(2-Bromoacetyl)-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one 1378390-29-4
Velpatasvir Intermediate 9-Bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one 1438383-89-1
Description: Velpatasvir, also known as GS-5816, is a potent and selective Hepatitis C virus NS5A inhibitor. GS-5816 has demonstrated pan-genotypic activity and a high barrier to resistance in HCV replicon assays. GS-5816 demonstrated pangenotypic antiviral activity in patients with genotype 1-4 HCV infection. It will be further evaluated in combination with other pangenotypic direct-acting antivirals to achieve the goal of developing a well-tolerated, highly effective treatment for all HCV genotypes.
Synonym: GS5816; GS-5816; GS 5816; Velpatasvir
IUPAC/Chemical Name: methyl ((R)-2-((2S,4S)-2-(5-(2-((2S,5S)-1-((methoxycarbonyl)-L-valyl)-5-methylpyrrolidin-2-yl)-1,11-dihydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-2-oxo-1-phenylethyl)carbamate
SMILES Code: O=C(OC)N[C@H](C1=CC=CC=C1)C(N2[C@H](C3=NC=C(C4=CC5=C(C6=CC7=CC=C8C(NC([C@H]9N(C([C@H](C(C)C)NC(OC)=O)=O)[C@@H](C)CC9)=N8)=C7C=C6OC5)C=C4)N3)C[C@H](COC)C2)=O
1: Kanda T. Interferon-free treatment for HCV-infected patients with decompensated cirrhosis. Hepatol Int. 2016 Jun 9. [Epub ahead of print] Review. PubMed PMID: 27282879.
2: Gane EJ, Schwabe C, Hyland RH, Yang Y, Svarovskaia E, Stamm LM, Brainard DM, McHutchison JG, Stedman CA. Efficacy of the Combination of Sofosbuvir, Velpatasvir, and the NS3/4A Protease Inhibitor GS-9857 in Treatment-naïve or Previously Treated Patients with HCV Genotype 1 or 3 Infections. Gastroenterology. 2016 May 27. pii: S0016-5085(16)34513-9. doi: 10.1053/j.gastro.2016.05.021. [Epub ahead of print] PubMed PMID: 27240903.
3: Schreiber J, McNally J, Chodavarapu K, Svarovskaia E, Moreno C. Treatment of a patient with genotype 7 HCV infection with sofosbuvir and velpatasvir. Hepatology. 2016 May 14. doi: 10.1002/hep.28636. [Epub ahead of print] PubMed PMID: 27177605.
4: Feld JJ, Zeuzem S. Sofosbuvir and Velpatasvir for Patients with HCV Infection. N Engl J Med. 2016 Apr 28;374(17):1688-9. PubMed PMID: 27135095.
5: Curry MP, Charlton M. Sofosbuvir and Velpatasvir for Patients with HCV Infection. N Engl J Med. 2016 Apr 28;374(17):1688. PubMed PMID: 27135094.
6: Assy N, Barhoum M. Sofosbuvir and Velpatasvir for Patients with HCV Infection. N Engl J Med. 2016 Apr 28;374(17):1687. doi: 10.1056/NEJMc1601160#SA1. PubMed PMID: 27119243.
7: Foster GR, Mangia A, Sulkowski M. Sofosbuvir and Velpatasvir for Patients with HCV Infection. N Engl J Med. 2016 Apr 28;374(17):1687-8. doi: 10.1056/NEJMc1601160. PubMed PMID: 27119242.
8: Smolders EJ, de Kanter CT, van Hoek B, Arends JE, Drenth JP, Burger DM. Pharmacokinetics, Efficacy, and Safety of Hepatitis C Virus Drugs in Patients with Liver and/or Renal Impairment. Drug Saf. 2016 Jul;39(7):589-611. doi: 10.1007/s40264-016-0420-2. Review. PubMed PMID: 27098247.
9: Majumdar A, Kitson MT, Roberts SK. Systematic review: current concepts and challenges for the direct-acting antiviral era in hepatitis C cirrhosis. Aliment Pharmacol Ther. 2016 Jun;43(12):1276-92. doi: 10.1111/apt.13633. Epub 2016 Apr 18. Review. PubMed PMID: 27087015.
10: Kahveci AS, Tahan V. Sofosbuvir and Velpatasvir: A complete pan-genotypic treatment for HCV patients. Turk J Gastroenterol. 2016 Mar;27(2):205-6. doi: 10.5152/tjg.2016.160000. PubMed PMID: 27015627.
11: Younossi ZM, Stepanova M, Feld J, Zeuzem S, Jacobson I, Agarwal K, Hezode C, Nader F, Henry L, Hunt S. Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: Results from ASTRAL-1 placebo-controlled trial. J Hepatol. 2016 Jul;65(1):33-9. doi: 10.1016/j.jhep.2016.02.042. Epub 2016 Mar 5. PubMed PMID: 26956698.
12: Gentile I, Scotto R, Zappulo E, Buonomo AR, Pinchera B, Borgia G. Investigational direct-acting antivirals in hepatitis C treatment: the latest drugs in clinical development. Expert Opin Investig Drugs. 2016 May;25(5):557-72. doi: 10.1517/13543784.2016.1161023. Epub 2016 Mar 21. PubMed PMID: 26934419.
13: Asselah T, Boyer N, Saadoun D, Martinot-Peignoux M, Marcellin P. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives. Liver Int. 2016 Jan;36 Suppl 1:47-57. doi: 10.1111/liv.13027. Review. PubMed PMID: 26725897.
14: Bourlière M, Adhoute X, Ansaldi C, Oules V, Benali S, Portal I, Castellani P, Halfon P. Sofosbuvir plus ledipasvir in combination for the treatment of hepatitis C infection. Expert Rev Gastroenterol Hepatol. 2015;9(12):1483-94. doi: 10.1586/17474124.2015.1111757. Epub 2015 Nov 23. PubMed PMID: 26595560.
15: Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourlière M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17. PubMed PMID: 26575258.
16: Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16. PubMed PMID: 26571066.
17: Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015 Dec 31;373(27):2618-28. doi: 10.1056/NEJMoa1512614. Epub 2015 Nov 16. PubMed PMID: 26569658.
18: Pianko S, Flamm SL, Shiffman ML, Kumar S, Strasser SI, Dore GJ, McNally J, Brainard DM, Han L, Doehle B, Mogalian E, McHutchison JG, Rabinovitz M, Towner WJ, Gane EJ, Stedman CA, Reddy KR, Roberts SK. Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med. 2015 Dec 1;163(11):809-17. doi: 10.7326/M15-1014. Epub 2015 Nov 10. PubMed PMID: 26551263.
19: Everson GT, Towner WJ, Davis MN, Wyles DL, Nahass RG, Thuluvath PJ, Etzkorn K, Hinestrosa F, Tong M, Rabinovitz M, McNally J, Brainard DM, Han L, Doehle B, McHutchison JG, Morgan T, Chung RT, Tran TT. Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med. 2015 Dec 1;163(11):818-26. doi: 10.7326/M15-1000. Epub 2015 Nov 10. PubMed PMID: 26551051.
20: Mogalian E, German P, Kearney BP, Yang CY, Brainard D, McNally J, Moorehead L, Mathias A. Use of Multiple Probes to Assess Transporter- and Cytochrome P450-Mediated Drug-Drug Interaction Potential of the Pangenotypic HCV NS5A Inhibitor Velpatasvir. Clin Pharmacokinet. 2016 May;55(5):605-13. doi: 10.1007/s40262-015-0334-7. PubMed PMID: 26519191.
CAS#: 1377049-84-7
Chemical Formula: C49H54N8O8
Exact Mass: 882.4065
Molecular Weight: 883.019
Elemental Analysis: C, 66.65; H, 6.16; N, 12.69; O, 14.49
EOS Med Chem produce Velpatasvir , 1377049-84-7, GS5816 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
Velpatasvir , 1377049-84-7, GS5816 Intermediates, EOS Med Chem have 8; Velpatasvir , 1377049-84-7, GS5816 Impurity we have 10, all from GMP, FDA plant.
Now Velpatasvir , 1377049-84-7, GS5816 DMF document is preparing.
Until 2016, Aug, Velpatasvir , 1377049-84-7, GS5816 more than produced 25kg API, 120kg Intermediates
Velpatasvir Intermediate (2S,4S)-4-(Methoxymethyl)-1,2-pyrrolidinedicarboxylic acid 1-(1,1-dimethylethyl) ester 1378388-16-9
Velpatasvir Intermediate (5S)-N-(Methoxycarbonyl)-L-valyl-5-methyl-L-proline 1335316-40-9
Velpatasvir Intermediate 3-(2-Bromoacetyl)-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one 1378390-29-4
Velpatasvir Intermediate 9-Bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one 1438383-89-1
Description: Velpatasvir, also known as GS-5816, is a potent and selective Hepatitis C virus NS5A inhibitor. GS-5816 has demonstrated pan-genotypic activity and a high barrier to resistance in HCV replicon assays. GS-5816 demonstrated pangenotypic antiviral activity in patients with genotype 1-4 HCV infection. It will be further evaluated in combination with other pangenotypic direct-acting antivirals to achieve the goal of developing a well-tolerated, highly effective treatment for all HCV genotypes.
Synonym: GS5816; GS-5816; GS 5816; Velpatasvir
IUPAC/Chemical Name: methyl ((R)-2-((2S,4S)-2-(5-(2-((2S,5S)-1-((methoxycarbonyl)-L-valyl)-5-methylpyrrolidin-2-yl)-1,11-dihydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-2-oxo-1-phenylethyl)carbamate
SMILES Code: O=C(OC)N[C@H](C1=CC=CC=C1)C(N2[C@H](C3=NC=C(C4=CC5=C(C6=CC7=CC=C8C(NC([C@H]9N(C([C@H](C(C)C)NC(OC)=O)=O)[C@@H](C)CC9)=N8)=C7C=C6OC5)C=C4)N3)C[C@H](COC)C2)=O
1: Kanda T. Interferon-free treatment for HCV-infected patients with decompensated cirrhosis. Hepatol Int. 2016 Jun 9. [Epub ahead of print] Review. PubMed PMID: 27282879.
2: Gane EJ, Schwabe C, Hyland RH, Yang Y, Svarovskaia E, Stamm LM, Brainard DM, McHutchison JG, Stedman CA. Efficacy of the Combination of Sofosbuvir, Velpatasvir, and the NS3/4A Protease Inhibitor GS-9857 in Treatment-naïve or Previously Treated Patients with HCV Genotype 1 or 3 Infections. Gastroenterology. 2016 May 27. pii: S0016-5085(16)34513-9. doi: 10.1053/j.gastro.2016.05.021. [Epub ahead of print] PubMed PMID: 27240903.
3: Schreiber J, McNally J, Chodavarapu K, Svarovskaia E, Moreno C. Treatment of a patient with genotype 7 HCV infection with sofosbuvir and velpatasvir. Hepatology. 2016 May 14. doi: 10.1002/hep.28636. [Epub ahead of print] PubMed PMID: 27177605.
4: Feld JJ, Zeuzem S. Sofosbuvir and Velpatasvir for Patients with HCV Infection. N Engl J Med. 2016 Apr 28;374(17):1688-9. PubMed PMID: 27135095.
5: Curry MP, Charlton M. Sofosbuvir and Velpatasvir for Patients with HCV Infection. N Engl J Med. 2016 Apr 28;374(17):1688. PubMed PMID: 27135094.
6: Assy N, Barhoum M. Sofosbuvir and Velpatasvir for Patients with HCV Infection. N Engl J Med. 2016 Apr 28;374(17):1687. doi: 10.1056/NEJMc1601160#SA1. PubMed PMID: 27119243.
7: Foster GR, Mangia A, Sulkowski M. Sofosbuvir and Velpatasvir for Patients with HCV Infection. N Engl J Med. 2016 Apr 28;374(17):1687-8. doi: 10.1056/NEJMc1601160. PubMed PMID: 27119242.
8: Smolders EJ, de Kanter CT, van Hoek B, Arends JE, Drenth JP, Burger DM. Pharmacokinetics, Efficacy, and Safety of Hepatitis C Virus Drugs in Patients with Liver and/or Renal Impairment. Drug Saf. 2016 Jul;39(7):589-611. doi: 10.1007/s40264-016-0420-2. Review. PubMed PMID: 27098247.
9: Majumdar A, Kitson MT, Roberts SK. Systematic review: current concepts and challenges for the direct-acting antiviral era in hepatitis C cirrhosis. Aliment Pharmacol Ther. 2016 Jun;43(12):1276-92. doi: 10.1111/apt.13633. Epub 2016 Apr 18. Review. PubMed PMID: 27087015.
10: Kahveci AS, Tahan V. Sofosbuvir and Velpatasvir: A complete pan-genotypic treatment for HCV patients. Turk J Gastroenterol. 2016 Mar;27(2):205-6. doi: 10.5152/tjg.2016.160000. PubMed PMID: 27015627.
11: Younossi ZM, Stepanova M, Feld J, Zeuzem S, Jacobson I, Agarwal K, Hezode C, Nader F, Henry L, Hunt S. Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: Results from ASTRAL-1 placebo-controlled trial. J Hepatol. 2016 Jul;65(1):33-9. doi: 10.1016/j.jhep.2016.02.042. Epub 2016 Mar 5. PubMed PMID: 26956698.
12: Gentile I, Scotto R, Zappulo E, Buonomo AR, Pinchera B, Borgia G. Investigational direct-acting antivirals in hepatitis C treatment: the latest drugs in clinical development. Expert Opin Investig Drugs. 2016 May;25(5):557-72. doi: 10.1517/13543784.2016.1161023. Epub 2016 Mar 21. PubMed PMID: 26934419.
13: Asselah T, Boyer N, Saadoun D, Martinot-Peignoux M, Marcellin P. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives. Liver Int. 2016 Jan;36 Suppl 1:47-57. doi: 10.1111/liv.13027. Review. PubMed PMID: 26725897.
14: Bourlière M, Adhoute X, Ansaldi C, Oules V, Benali S, Portal I, Castellani P, Halfon P. Sofosbuvir plus ledipasvir in combination for the treatment of hepatitis C infection. Expert Rev Gastroenterol Hepatol. 2015;9(12):1483-94. doi: 10.1586/17474124.2015.1111757. Epub 2015 Nov 23. PubMed PMID: 26595560.
15: Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourlière M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17. PubMed PMID: 26575258.
16: Feld JJ, Jacobson IM, Hézode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16. PubMed PMID: 26571066.
17: Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015 Dec 31;373(27):2618-28. doi: 10.1056/NEJMoa1512614. Epub 2015 Nov 16. PubMed PMID: 26569658.
18: Pianko S, Flamm SL, Shiffman ML, Kumar S, Strasser SI, Dore GJ, McNally J, Brainard DM, Han L, Doehle B, Mogalian E, McHutchison JG, Rabinovitz M, Towner WJ, Gane EJ, Stedman CA, Reddy KR, Roberts SK. Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med. 2015 Dec 1;163(11):809-17. doi: 10.7326/M15-1014. Epub 2015 Nov 10. PubMed PMID: 26551263.
19: Everson GT, Towner WJ, Davis MN, Wyles DL, Nahass RG, Thuluvath PJ, Etzkorn K, Hinestrosa F, Tong M, Rabinovitz M, McNally J, Brainard DM, Han L, Doehle B, McHutchison JG, Morgan T, Chung RT, Tran TT. Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med. 2015 Dec 1;163(11):818-26. doi: 10.7326/M15-1000. Epub 2015 Nov 10. PubMed PMID: 26551051.
20: Mogalian E, German P, Kearney BP, Yang CY, Brainard D, McNally J, Moorehead L, Mathias A. Use of Multiple Probes to Assess Transporter- and Cytochrome P450-Mediated Drug-Drug Interaction Potential of the Pangenotypic HCV NS5A Inhibitor Velpatasvir. Clin Pharmacokinet. 2016 May;55(5):605-13. doi: 10.1007/s40262-015-0334-7. PubMed PMID: 26519191.
