EOS Med Chem produce Dolutegravir (GSK1349572) 1051375-16-6 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Dolutegravir (GSK1349572)

CAS#: 1051375-16-6

Chemical Formula: C20H19F2N3O5

Exact Mass: 419.12928

Molecular Weight: 419.38

Elemental Analysis: C, 57.28; H, 4.57; F, 9.06; N, 10.02; O, 19.08

EOS Med Chem produce Dolutegravir (GSK1349572) 1051375-16-6 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Dolutegravir (GSK1349572) 1051375-16-6 Intermediates, EOS Med Chem have 8; Dolutegravir (GSK1349572) 1051375-16-6 Impurity we have 10, all from GMP, FDA plant.

Now Dolutegravir (GSK1349572) 1051375-16-6 DMF document is preparing.

Until 2016, Aug, Dolutegravir (GSK1349572) 1051375-16-6 more than produced 25kg API, 120kg Intermediates

Dolutegravir Intermediate (R)-Homo-beta-alanine 3775-73-7

Dolutegravir Intermediate R-3-amnio-butanol 61477-40-5

Dolutegravir Intermediate (4R,12aS)-7-(benzyloxy)-N-(2,4-difluorobenzyl)-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide 1206102-11-5

Dolutegravir Intermediate 3-(Benzyloxy)-4-oxo-4h-pyran-2-carboxylic acid 1206102-08-0

Description: Dolutegravir, also known as GSK1349572, is an FDA-approved drug[3] for the treatment of HIV infection. It can be used to treat HIV-infected adults who have never taken HIV therapy (treatment-naïve) and HIV-infected adults who have previously taken HIV therapy (treatment-experienced), including those who have been treated with other integrase strand transfer inhibitors. Tivicay is also approved for children ages 12 years and older weighing at least 40 kilograms (kg) who are treatment-naïve or treatment-experienced but have not previously taken other integrase strand transfer inhibitors.

Synonym: Dolutegravir; GSK1349572; GSK-1349572; GSK 1349572. Tivicay.

IUPAC/Chemical Name: (4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide

SMILES Code: O=C(C1=CN(C2=C(O)C1=O)C[C@]3([H])OCC[C@@H](C)N3C2=O)NCC4=CC=C(F)C=C4F

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).

1: Llibre JM, Clotet B. Once-daily single-tablet regimens: a long and winding road to excellence in antiretroviral treatment. AIDS Rev. 2012 Jul;14(3):168-78. PubMed PMID: 22833060.

2: Rhodes MC, Laffan S, Genell C, Gower J, Maier C, Fukushima T, Nichols G, Eaton Bassiri A. Assessing a Theoretical Risk of Dolutegravir-Induced Developmental Immunotoxicity in Juvenile Rats. Toxicol Sci. 2012 Jul 12. [Epub ahead of print] PubMed PMID: 22790968.

3: Adams JL, Greener BN, Kashuba AD. Pharmacology of HIV integrase inhibitors. Curr Opin HIV AIDS. 2012 Jul 19. [Epub ahead of print] PubMed PMID: 22789987.

4: Lennox JL. The use of HIV-1 integrase inhibitors in antiretroviral naive patients. Curr Opin HIV AIDS. 2012 Jul 19. [Epub ahead of print] PubMed PMID: 22789985.

5: Shamroe CL, Bookstaver PB, Rokas KE, Weissman SB. Update on raltegravir and the development of new integrase strand transfer inhibitors. South Med J. 2012 Jul;105(7):370-8. PubMed PMID: 22766666.

6: Saladini F, Meini G, Bianco C, Monno L, Punzi G, Pecorari M, Borghi V, Di Pietro M, Filice G, Gismondo MR, Micheli V, Penco G, Carli T, De Luca A, Zazzi M; for the ARCA Collaborative Group. Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naïve and pretreated patients. Clin Microbiol Infect. 2012 May 28. doi: 10.1111/j.1469-0691.2012.03917.x. [Epub ahead of print] PubMed PMID: 22716970.

7: Quashie PK, Sloan RD, Wainberg MA. Novel therapeutic strategies targeting HIV integrase. BMC Med. 2012 Apr 12;10:34. Review. PubMed PMID: 22498430; PubMed Central PMCID: PMC3348091.

8: Nguyen HL, Ruxrungtham K, Delaugerre C. Genetic barrier to the development of resistance to integrase inhibitors in HIV-1 subtypes CRF01_AE and B. Intervirology. 2012;55(4):287-95. Epub 2012 Mar 23. PubMed PMID: 22456540.

9: Chen S, Min SS, Peppercorn A, Borland J, Lou Y, Song I, Fujiwara T, Piscitelli SC. Effect of a single supratherapeutic dose of dolutegravir on cardiac repolarization. Pharmacotherapy. 2012 Apr;32(4):333-9. doi: 10.1002/j.1875-9114.2012.01033.x. Epub 2012 Mar 15. PubMed PMID: 22422361.

10: Katlama C, Murphy R. Dolutegravir for the treatment of HIV. Expert Opin Investig Drugs. 2012 Apr;21(4):523-30. Epub 2012 Mar 2. Review. PubMed PMID: 22380682.

EOS Med Chem produce Ledipasvir GS5885 1256388-51-8 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Ledipasvir

CAS#: 1256388-51-8

Chemical Formula: C49H54F2N8O6

Exact Mass: 888.41344

Molecular Weight: 889.0

Elemental Analysis: C, 66.20; H, 6.12; F, 4.27; N, 12.60; O, 10.80

EOS Med Chem produce Ledipasvir  GS5885  1256388-51-8 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Ledipasvir  GS5885  1256388-51-8 Intermediates, EOS Med Chem have 8; Ledipasvir  GS5885  1256388-51-8 Impurity we have 10, all from GMP, FDA plant.

Now Ledipasvir  GS5885  1256388-51-8 DMF document is preparing.

Until 2016, Aug, Ledipasvir  GS5885  1256388-51-8 more than produced 25kg API, 120kg Intermediates

Ledipasvir Intermediate Led-B 1378387-81-5  1-(7-Bromo-9,9-difluoro-9H-fluoren-2-yl)-2-chloroethanone

Ledipasvir Intermediate Led-A-1 1129634-44-1  (S)-5-(tert-Butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid

Ledipasvir Intermediate Led-C-3 291775-59-2  (1R,3S,4S)-N-Boc-2-azabicyclo[2.2.1]heptane-3-carboxylic acid

Ledipasvir Intermediate Led N-3 1441670-89-8  (6S)-6-[5-(7-Bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl]-5-azaspiro[2.4]heptane-5-carboxylic acid 1,1-dimethylethyl ester

Ledipasvir Intermediate Led-C 1256387-87-7  (1R,3S,4S)-3-[6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl ester

Ledipasvir Intermediate Led N-1.2 74761-42-5  (S)-2-(Methoxycarbonylamino)-3-methylbutanoic acid

Ledipasvir Intermediate Led-C-1 1256387-74-2  (1R,3S,4S)-3-(6-Bromo-1H-benzimidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl ester

Ledipasvir Intermediate Led-A 1441673-92-2  (6S)-5-Azaspiro[2.4]heptane-5,6-dicarboxylic acid 5-(1,1-dimethylethyl) ester potassium salt (1:1)

Name   (1R,3S,4S)-3-[6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl ester" 1256387-87-7

Ledipasvir  Intermediate   (1R,3S,4S)-3-(6-Bromo-1H-benzimidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl ester 1256387-74-2

Description: Ledipasvir, also known as GS-5885; is an inhibitor of the hepatitis C virus NS5A protein and is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. On October 10, 2014 the FDA approved the combination product ledipasvir 90 mg/sofosbuvir 400 mg (trade name Harvoni). The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin. (http://en.wikipedia.org/wiki/Ledipasvir)

Synonym: GS5885; GS-5885; GS 5885; Ledipasvir; trade name: Harvoni.

IUPAC/Chemical Name: Methyl N-[(2S)-1-[(6S)-6-[5-[9,9-Difluoro-7-[2-[(1S,2S,4R)-3-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-3-azabicyclo[2.2.1]heptan-2-yl]-3H-benzimidazol-5-yl]fluoren-2-yl]-1H-imidazol-2-yl]-5-azaspiro[2.4]heptan-5-yl]-3-methyl-1-oxobutan-2-yl]carbamate

SMILES Code: O=C(OC)N[C@@H](C(C)C)C(N([C@H](C1=NC=C(C2=CC(C(F)(F)C3=C4C=CC(C5=CC=C6C(NC([C@@H]7[C@@](C8)([H])CC[C@@]8([H])N7C([C@@H](NC(OC)=O)C(C)C)=O)=N6)=C5)=C3)=C4C=C2)N1)C9)CC%109CC%10)=O

1: Younossi ZM, Stepanova M, Marcellin P, Afdhal N, Kowdley KV, Zeuzem S, Hunt SL. Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the Ion-1, 2 and 3 clinical trials. Hepatology. 2015 Jan 27. doi: 10.1002/hep.27724. [Epub ahead of print] PubMed PMID: 25627448.

2: Younossi ZM, Park H, Saab S, Ahmed A, Dieterich D, Gordon SC. Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther. 2015 Jan 26. doi: 10.1111/apt.13081. [Epub ahead of print] PubMed PMID: 25619871.

3: Smith MA, Chan J, Mohammad RA. Ledipasvir-Sofosbuvir: Interferon-/Ribavirin-Free Regimen for Chronic Hepatitis C Virus Infection. Ann Pharmacother. 2014 Dec 16. pii: 1060028014563952. [Epub ahead of print] Review. PubMed PMID: 25515863.

4: A combination of ledipasvir and sofosbuvir (Harvoni) for hepatitis C. Med Lett Drugs Ther. 2014 Nov 10;56(1455):111-2. PubMed PMID: 25372848.

5: A SPECIAL MEETING REVIEW EDITION: Advances in the Treatment of Hepatitis C Virus Infection from The Liver Meeting 2013: The 64th Annual Meeting of the American Association for the Study of Liver DiseasesNovember 1-5, 2013 • Washington DCSpecial Reporting on:• Simeprevir plus Sofosbuvir with or without Ribavirin Produces High SVR Rates in Genotype 1 HCV Infection• Novel Interferon- and Ribavirin-Free Regimen Results in SVR12 Rates of Over 90% in HCV Genotype 1b Infection• Studies Confirm Efficacy of Adjunctive Simeprevir in Difficult-to-Treat HCV Genotype 1 Subpopulations• All-Oral Therapy with Sofosbuvir Plus Ribavirin Produces High SVR Rates in Patients Coinfected with HCV and HIV• Faldaprevir Combined with Pegylated Interferon and Ribavirin Demonstrates High Efficacy in DifficuIt-to-Treat HCV Infection• Once Daily Sofosbuvir/Ledipasvir Combination Elicits Rapid Decline in HCV RNAPLUS Meeting Abstract Summaries With Expert Commentary by: Ira M. Jacobson, MDWeill Cornell Medical CollegeNew York, New York. Gastroenterol Hepatol (N Y). 2014 Jan;10(1 Suppl 1):1-19. PubMed PMID: 25337060; PubMed Central PMCID: PMC4201083.

6: Gentile I, Borgia G. Ledipasvir/Sofosbuvir administration achieves very high rate of viral clearance in patients with HCV genotype 1 infection without cirrhosis, regardless of ribavirin co-administration or length of treatment. Evid Based Med. 2014 Dec;19(6):223-4. doi: 10.1136/ebmed-2014-110051. Epub 2014 Jul 15. PubMed PMID: 25028605.

7: German P, Moorehead L, Pang P, Vimal M, Mathias A. Lack of a clinically important pharmacokinetic interaction between sofosbuvir or ledipasvir and hormonal oral contraceptives norgestimate/ethinyl estradiol in HCV-uninfected female subjects. J Clin Pharmacol. 2014 Nov;54(11):1290-8. doi: 10.1002/jcph.346. Epub 2014 Jun 24. PubMed PMID: 24925712.

8: Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Bräu N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11. PubMed PMID: 24725239.

9: Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11. PubMed PMID: 24725238.

10: Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, Shiffman ML, Schiff E, Ghalib R, Ryan M, Rustgi V, Chojkier M, Herring R, Di Bisceglie AM, Pockros PJ, Subramanian GM, An D, Svarovskaia E, Hyland RH, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Pound D, Fried MW; ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88. doi: 10.1056/NEJMoa1402355. Epub 2014 Apr 10. PubMed PMID: 24720702.

11: Gentile I, Buonomo AR, Borgia F, Castaldo G, Borgia G. Ledipasvir : a novel synthetic antiviral for the treatment of HCV infection. Expert Opin Investig Drugs. 2014 Apr;23(4):561-71. doi: 10.1517/13543784.2014.892581. Epub 2014 Mar 4. Review. PubMed PMID: 24593285.

12: Wyles DL, Rodriguez-Torres M, Lawitz E, Shiffman ML, Pol S, Herring RW, Massetto B, Kanwar B, Trenkle JD, Pang PS, Zhu Y, Mo H, Brainard DM, Subramanian GM, McHutchison JG, Habersetzer F, Sulkowski MS. All-oral combination of ledipasvir, vedroprevir, tegobuvir, and ribavirin in treatment-naïve patients with genotype 1 HCV infection. Hepatology. 2014 Jul;60(1):56-64. doi: 10.1002/hep.27053. Epub 2014 May 28. PubMed PMID: 24501005.

13: Link JO, Taylor JG, Xu L, Mitchell M, Guo H, Liu H, Kato D, Kirschberg T, Sun J, Squires N, Parrish J, Keller T, Yang ZY, Yang C, Matles M, Wang Y, Wang K, Cheng G, Tian Y, Mogalian E, Mondou E, Cornpropst M, Perry J, Desai MC. Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection. J Med Chem. 2014 Mar 13;57(5):2033-46. doi: 10.1021/jm401499g. Epub 2014 Jan 10. PubMed PMID: 24320933.

14: Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Subramanian GM, Symonds WT, McHutchison JG, Pang PS. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology. 2014 Mar;146(3):736-743.e1. doi: 10.1053/j.gastro.2013.11.007. Epub 2013 Nov 18. PubMed PMID: 24262278.

15: Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5. Erratum in: Lancet. 2014 Mar 8;383(9920):870. PubMed PMID: 24209977.

EOS Med Chem produce Velpatasvir , 1377049-84-7, GS5816 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

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.

EOS Med Chem produce Safinamide, FCE 26743, 133865-89-1 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok

Name: Safinamide
CAS#: 133865-89-1
Chemical Formula: C17H19FN2O2
Exact Mass: 302.1431
Molecular Weight: 302.3494
Elemental Analysis: C, 67.53; H, 6.33; F, 6.28; N, 9.27; O, 10.58

EOS Med Chem produce Safinamide, FCE 26743,  133865-89-1 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
Safinamide, FCE 26743,  133865-89-1 Intermediates, EOS Med Chem have 8; Safinamide, FCE 26743,  133865-89-1 Impurity we have 10, all from GMP, FDA plant.
Now Safinamide, FCE 26743,  133865-89-1 DMF document is preparing.
Until 2016, Aug, Safinamide, FCE 26743,  133865-89-1 more than produced 25kg API, 120kg Intermediates


Description: Safinamide, also known as FCE-26743 and EMD-1195686, is a drug indicated for the treatment of Parkinson's disease with multiple methods of action. Potential additional uses might be restless legs syndrome (RLS) and epilepsy. Safinamide is a reversible and selective monoamine oxidase B inhibitor, reducing degradation of dopamine, and a glutamate release inhibitor. It also inhibits dopamine reuptake. Additionally, safinamide blocks sodium and calcium channels. Safinamide has been approved by the European Medicines Agency for the treatment of adult patients with idiopathic Parkinson’s disease as add-on therapy to a stable dose of Levodopa (L-dopa) alone or in combination with other PD drugs in patients with mid-to-late-stage fluctuating disease.
Synonym: FCE-26743; FCE 26743; FCE26743; EMD-1195686; EMD 1195686; EMD1195686; Safinamide. Xadago
IUPAC/Chemical Name: (S)-2-((4-((3-fluorobenzyl)oxy)benzyl)amino)propanamide
SMILES Code: C[C@H](NCC1=CC=C(OCC2=CC=CC(F)=C2)C=C1)C(N)=O

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).

1: Stocchi F, Torti M. Adjuvant therapies for Parkinson's disease: critical evaluation of safinamide. Drug Des Devel Ther. 2016 Feb 5;10:609-18. doi: 10.2147/DDDT.S77749. eCollection 2016. Review. PubMed PMID: 26917951; PubMed Central PMCID: PMC4751980.
2: Cattaneo C, Sardina M, Bonizzoni E. Safinamide as Add-On Therapy to Levodopa in Mid- to Late-Stage Parkinson's Disease Fluctuating Patients: Post hoc Analysesof Studies 016 and SETTLE. J Parkinsons Dis. 2016;6(1):165-73. doi: 10.3233/JPD-150700. PubMed PMID: 26889632; PubMed Central PMCID: PMC4927927.
3: Perez-Lloret S, Rascol O. The safety and efficacy of safinamide mesylate for the treatment of Parkinson's disease. Expert Rev Neurother. 2016;16(3):245-58. doi: 10.1586/14737175.2016.1150783. Epub 2016 Feb 19. PubMed PMID: 26849427.
4: Rasheed MZ, Tabassum H, Parvez S. Mitochondrial permeability transition pore: a promising target for the treatment of Parkinson's disease. Protoplasma. 2016 Jan 29. [Epub ahead of print] PubMed PMID: 26825389.
5: Müller T. Safinamide for symptoms of Parkinson's disease. Drugs Today (Barc). 2015 Nov;51(11):653-9. doi: 10.1358/dot.2015.51.11.2414529. Review. PubMed PMID: 26744740.
6: Fabbri M, Rosa MM, Abreu D, Ferreira JJ. Clinical pharmacology review of safinamide for the treatment of Parkinson's disease. Neurodegener Dis Manag. 2015 Dec;5(6):481-96. doi: 10.2217/nmt.15.46. Epub 2015 Nov 20. PubMed PMID: 26587996.
7: Cattaneo C, Ferla RL, Bonizzoni E, Sardina M. Long-Term Effects of Safinamide on Dyskinesia in Mid- to Late-Stage Parkinson's Disease: A Post-Hoc Analysis. J Parkinsons Dis. 2015;5(3):475-81. doi: 10.3233/JPD-150569. PubMed PMID: 26406127; PubMed Central PMCID: PMC4923744.
8: Sadeghian M, Mullali G, Pocock JM, Piers T, Roach A, Smith KJ. Neuroprotection by safinamide in the 6-hydroxydopamine model of Parkinson's disease. Neuropathol Appl Neurobiol. 2016 Aug;42(5):423-35. doi: 10.1111/nan.12263. Epub 2015 Sep 25. PubMed PMID: 26300398.
9: Reichmann H. Modern treatment in Parkinson's disease, a personal approach. J Neural Transm (Vienna). 2016 Jan;123(1):73-80. doi: 10.1007/s00702-015-1441-1. Epub 2015 Aug 21. PubMed PMID: 26293352.
10: Rascol O, Perez-Lloret S, Ferreira JJ. New treatments for levodopa-induced motor complications. Mov Disord. 2015 Sep 15;30(11):1451-60. doi: 10.1002/mds.26362. Epub 2015 Aug 21. Review. PubMed PMID: 26293004.
11: Robakis D, Fahn S. Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson's Disease. CNS Drugs. 2015 Jun;29(6):433-41. doi: 10.1007/s40263-015-0249-8. Review. PubMed PMID: 26164425.
12: Martinez-Martin P, Rodriguez-Blazquez C, Forjaz MJ, Kurtis MM. Impact of Pharmacotherapy on Quality of Life in Patients with Parkinson's Disease. CNS Drugs. 2015 May;29(5):397-413. doi: 10.1007/s40263-015-0247-x. Review. PubMed PMID: 25968563.
13: Deeks ED. Safinamide: first global approval. Drugs. 2015 Apr;75(6):705-11. doi: 10.1007/s40265-015-0389-7. Review. PubMed PMID: 25851099.
14: Chung JY, Lee JW, Ryu CH, Min HK, Yoon YJ, Lim MJ, Park CH. 1-[2-(4-Benzyloxyphenoxy)Ethyl]Imidazole inhibits monoamine oxidase B and protects against neuronal loss and behavioral impairment in rodent models of Parkinson's disease. J Neurosci Res. 2015 Aug;93(8):1267-78. doi: 10.1002/jnr.23577. Epub 2015 Feb 24. PubMed PMID: 25711470.
15: Cada DJ, Baker DE. Oritavancin diphosphate. Hosp Pharm. 2014 Dec;49(11):1049-60. doi: 10.1310/hjp4911-1049. PubMed PMID: 25673895; PubMed Central PMCID: PMC4319806.
16: Kakkar AK, Dahiya N. Management of Parkinson׳s disease: Current and future pharmacotherapy. Eur J Pharmacol. 2015 Mar 5;750:74-81. doi: 10.1016/j.ejphar.2015.01.030. Epub 2015 Jan 28. Review. PubMed PMID: 25637088.
17: Park KD, Yang XF, Dustrude ET, Wang Y, Ripsch MS, White FA, Khanna R, Kohn H. Chimeric agents derived from the functionalized amino acid, lacosamide, and the α-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosamide and safinamide. ACS Chem Neurosci. 2015 Feb 18;6(2):316-30. doi: 10.1021/cn5002182. Epub 2014 Dec 9. PubMed PMID: 25418676; PubMed Central PMCID: PMC4372064.
18: Schaeffer E, Pilotto A, Berg D. Pharmacological strategies for the management of levodopa-induced dyskinesia in patients with Parkinson's disease. CNS Drugs. 2014 Dec;28(12):1155-84. doi: 10.1007/s40263-014-0205-z. Review. PubMed PMID: 25342080.
19: Vijverman AC, Fox SH. New treatments for the motor symptoms of Parkinson's disease. Expert Rev Clin Pharmacol. 2014 Nov;7(6):761-77. doi: 10.1586/17512433.2014.966812. Review. PubMed PMID: 25318835.
20: Kandadai RM, Jabeen SA, Kanikannan MA, Borgohain R. Safinamide for the treatment of Parkinson's disease. Expert Rev Clin Pharmacol. 2014 Nov;7(6):747-59. doi: 10.1586/17512433.2014.968555. Epub 2014 Oct 10. Review. PubMed PMID: 25300164.

Biggest supplier Upadacitinib (ABT-494) CAS#: 1310726-60-3

EOS Med Chem is the world first supplier of Upadacitinib (ABT-494) 1310726-60-3.

We start this Upadacitinib (ABT-494) 1310726-60-3 in 2015, until now, we could supply Upadacitinib (ABT-494) 1310726-60-3 and Intermediates. Produced total 20kg.

Upadacitinib (ABT-494) 1310726-60-3, Assay more than 99%, HPLC, NMR, MS is provided.

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

Keep Upadacitinib (ABT-494) 1310726-60-3 100g in stock.

Name: Upadacitinib (ABT-494)
CAS#: 1310726-60-3
Chemical Formula: C17H19F3N6O
Exact Mass: 380.1572
Molecular Weight: 380.3752
Elemental Analysis: C, 53.68; H, 5.04; F, 14.98; N, 22.09; O, 4.21

Description: Upadacitinib, also known as ABT-494, is a potent and selective JAK inhibitors in development for rheumatoid arthritis. ABT-494 is approximately 74 fold selective for Jak1 over Jak2 in cellular assays dependent on specific, relevant cytokines. ABT-494 demonstrates efficacy in rat arthritis models. Preliminary evidence suggests that compared to tofacitinib, ABT-494 may spare Jak2 and Jak3 dependent signaling.
Synonym: ABT-494; ABT 494; ABT494. Upadacitinib.
IUPAC/Chemical Name: (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
SMILES Code: O=C(N1C[C@@H](CC)[C@@H](C2=CN=C3C=NC(NC=C4)=C4N32)C1)NCC(F)(F)F

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, not in water
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).

1: Norman P. Selective JAK inhibitors in development for rheumatoid arthritis.
Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77. doi:
10.1517/13543784.2014.918604. Epub 2014 May 12. Review. PubMed PMID: 24818516.

Biggest Manufacturer Acalabrutinib (ACP-196) CAS#: 1420477-60-6 and Intermediates.

Name: Acalabrutinib (ACP-196)

CAS#: 1420477-60-6

Chemical Formula: C26H23N7O2

Exact Mass: 465.19132

Molecular Weight: 465.52

Elemental Analysis: C, 67.08; H, 4.98; N, 21.06; O, 6.87

EOS Med Chem produce Acalabrutinib (ACP-196) in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

First supplier who could produce EE, Optical purity 99.5 more, stock more than 20KG.

Acalabrutinib (ACP-196) Intermediates, EOS Med Chem have 8; Acalabrutinib (ACP-196) Impurity we have 10, all from GMP, FDA plant.

Now Acalabrutinib (ACP-196) DMF document is preparing.

Until 2016, Aug, Acalabrutinib (ACP-196) more than produced 25kg API, 120kg Intermediates, world biggest supplier.

Acalabrutinib (ACP-196) Intermediate 1420478-90-5,(S)-4-(8-amino-3-(pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1420478-89-2,(S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1420478-88-1, (S)-benzyl 2-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1420478-87-0,(S)-benzyl 2-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1418307-18-2, (S)-benzyl 2-(8-chloroimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1418307-17-1, (S)-benzyl 2-((3-chloropyrazin-2-yl)methylcarbamoyl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 771581-15-8,  2-Aminomethyl-3-chloropyrazine, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 55557-52-3, 3-Chloropyrazine-2-carbonitrile, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1383385-64-5, No Name, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 180516-87-4, 4-Carboxylphenylboronic acid pinacol ester, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

2017 China CPHI: E1M35

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

労働時間: Beijing Time 4:00AM~11:00PM

郵箱: info@eosmedchem.com ; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp & Wechat: +8618653174435

住所: Diaozhen Chemical Industrial Park, Jinan City, China

Skype: willgutian

QQ: 2393923585

Description: Acalabrutinib, also known as ACP-196, is an orally available inhibitor of Bruton’s tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

Synonym: ACP-196; ACP196; ACP 196; Acalabrutinib

IUPAC/Chemical Name: (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide

Acalabrutinib is a potent and selective BTK (Bruton's tyrosine kinase) inhibitor. BTK is a cytoplasmic, non-receptor tyrosine kinase that transmits signals from a variety of cell-surface molecules, including the B-cell receptor (BCR) and tissue homing receptors. Genetic BTK deletion causes B-cell immunodeficiency in humans and mice, making this kinase an attractive therapeutic target for B-cell disorders. BTK inhibitors targeting B cell receptor signaling and other survival mechanism showed great promise for the treatment of chronic lymphocytic leukemia (CLL)s holds great promise.

As of 2015 it is in late stage clinical trials for relapsed chronic lymphocytic leukemia. Interim results are encouraging : 95% overall response rate. It is also in another 20 clinical trials (alone and in combination) for various cancers.

1: Maly J, Blachly JS. Chronic Lymphocytic Leukemia: Exploiting Vulnerabilities with Targeted Agents. Curr Hematol Malig Rep. 2016 Feb 11. [Epub ahead of print] PubMed PMID: 26893063.

2: Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):323-32. doi: 10.1056/NEJMoa1509981. Epub 2015 Dec 7. PubMed PMID: 26641137.

EOS Med Chem produce Venetoclax (ABT199) 1257044-40-8 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok

Name: Venetoclax (ABT199)
CAS#: 1257044-40-8
Chemical Formula: C45H50ClN7O7S
Exact Mass: 867.3181
Molecular Weight: 868.44
Elemental Analysis: C, 62.24; H, 5.80; Cl, 4.08; N, 11.29; O, 12.90; S, 3.69

EOS Med Chem produce Venetoclax (ABT199) 1257044-40-8 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
Venetoclax (ABT199) 1257044-40-8 Intermediates, EOS Med Chem have 8; Venetoclax (ABT199) 1257044-40-8 Impurity we have 10, all from GMP, FDA plant.
Now Venetoclax (ABT199) 1257044-40-8 DMF document is preparing.
Until 2016, Aug, Venetoclax (ABT199) 1257044-40-8 more than produced 25kg API, 120kg Intermediates

ABT-199, Venetoclax;  CAS 1257044-40-8

Venetoclax (ABT199) Intermediate 4-fluoro-3-nitrobenzenesulfonamide  CAS  406233-31-6
Venetoclax (ABT199) Intermediate 3-Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide       CAS 1228779-96-1
Venetoclax (ABT199) Intermediate 1H-Pyrrolo[2,3-b]pyridin-5-ol      CAS 98549-88-3
Venetoclax (ABT199) Intermediate Ethyl2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoate  CAS 1630101-74-4
Venetoclax (ABT199) Intermediate Methyl 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoate     CAS 1235865-75-4
Venetoclax (ABT199) Intermediate 3,3-Dimethylcyclohexanone  CAS 2979-19-3
Venetoclax (ABT199) Intermediate (4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methanol CAS 1228837-05-5
Venetoclax (ABT199) Intermediate 1-[[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazine   CAS 1228780-72-0
Venetoclax (ABT199) Intermediate Tert-butyl4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carboxylate     CAS 1228780-71-9
Venetoclax (ABT199) Intermediate 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid CAS 1235865-77-6

Description: Venetoclax, also known as ABT-199 or GDC0199, is an orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells.
Synonym: ABT199; ABT-199; ABT 199; GDC0199; GDC0199; GDC 0199; RG7601; RG7601; RG 7601. Venetoclax.
IUPAC/Chemical Name: 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
SMILES Code: O=C(NS(=O)(C1=CC=C(NCC2CCOCC2)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCN(CC5=C(C6=CC=C(Cl)C=C6)CC(C)(C)CC5)CC4)C=C3OC7=CN=C(NC=C8)C8=C7

GDC-0199 (RG7601) is a novel small molecule Bcl-2 selective inhibitor designed to restore apoptosis, also known as programmed cell death, by blocking the function of a pro-survival Bcl-2 family protein. The Bcl-2 family proteins, which are expressed at high levels in many tumors, play a central role in regulating apoptosis and, consequently, are thought to impact tumor formation, tumor growth and resistance.

1: Seymour J. ABT-199 for Chronic Lymphocytic Leukemia. Clin Adv Hematol Oncol. 2014 Oct;12(10):698-700. PubMed PMID: 25658896.
2: Choudhary GS, Al-Harbi S, Mazumder S, Hill BT, Smith MR, Bodo J, Hsi ED, Almasan A. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis. 2015 Jan 15;6:e1593. doi: 10.1038/cddis.2014.525. PubMed PMID: 25590803.
3: Cao Y, Yang G, Hunter ZR, Liu X, Xu L, Chen J, Tsakmaklis N, Hatjiharissi E, Kanan S, Davids MS, Castillo JJ, Treon SP. The BCL2 antagonist ABT-199 triggers apoptosis, and augments ibrutinib and idelalisib mediated cytotoxicity in CXCR4(Wild-type) and CXCR4(WHIM) mutated Waldenstrom macroglobulinaemia cells. Br J Haematol. 2015 Jan 12. doi: 10.1111/bjh.13278. [Epub ahead of print] PubMed PMID: 25582069.
4: Johnson-Farley N, Veliz J, Bhagavathi S, Bertino JR. ABT-199, a BH3 mimetic that specifically targets Bcl-2, enhances the antitumor activity of chemotherapy, bortezomib and JQ1 in "double hit" lymphoma cells. Leuk Lymphoma. 2015 Jan 28:1-7. [Epub ahead of print] PubMed PMID: 25373508.
5: Ko TK, Chuah CT, Huang JW, Ng KP, Ong ST. The BCL2 inhibitor ABT-199 significantly enhances imatinib-induced cell death in chronic myeloid leukemia progenitors. Oncotarget. 2014 Oct 15;5(19):9033-8. PubMed PMID: 25333252; PubMed Central PMCID: PMC4253416.
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EOS Med Chem produce Tirabrutinib HCl,ONO4059, 1439901-97-9 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Tirabrutinib HCl

CAS#: 1439901-97-9 (HCl)

Chemical Formula: C25H23ClN6O3

Exact Mass:

Molecular Weight: 490.948

Elemental Analysis: C, 61.16; H, 4.72; Cl, 7.22; N, 17.12; O, 9.78

EOS Med Chem produce Tirabrutinib HCl,ONO4059, 1439901-97-9 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Tirabrutinib HCl,ONO4059, 1439901-97-9 Intermediates, EOS Med Chem have 8; Tirabrutinib HCl,ONO4059, 1439901-97-9 Impurity we have 10, all from GMP, FDA plant.

Now Tirabrutinib HCl,ONO4059, 1439901-97-9 DMF document is preparing.

Until 2016, Aug, Tirabrutinib HCl,ONO4059, 1439901-97-9 more than produced 25kg API, 120kg Intermediates

Description: Tirabrutinib HCl, also known as ONO-4059 HCl, is a potent and orally active Bruton agammaglobulinemia tyrosine kinase (BTK) in hibitor. Upon administration, ONO-4059 covalently binds to BTK within B cells, thereby preventing B-cell receptor signaling and impeding B-cell development. As a result, this agent may inhibit the proliferation of B-cell malignancies. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

Synonym: ONO-4059 HCl; ONO4059; ONO 4059; ONO-4059; GS 4059; GS-4059; GS4059; ONO-WG-307; Tirabrutinib

IUPAC/Chemical Name: (R)-6-amino-9-(1-(but-2-ynoyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one hydrochloride

SMILES Code: O=C(N1C[C@@H](CC1)N(C2=O)C3=NC=NC(N)=C3N2C4=CC=C(C=C4)OC5=CC=CC=C5)C#CC.[H]Cl

Related CAS#

1439901-97-9 (ONO-4059 HCl);

1351636-18-4 (ONO-4059 free base).

1351635-67-0 (ONO-4059 analog).

CID: PMC4876096.

2: Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016 Mar 9;9:21. doi: 10.1186/s13045-016-0250-9. PubMed PMID: 26957112; PubMed Central PMCID: PMC4784459.

3: Walter HS, Rule SA, Dyer MJ, Karlin L, Jones C, Cazin B, Quittet P, Shah N, Hutchinson CV, Honda H, Duffy K, Birkett J, Jamieson V, Courtenay-Luck N, Yoshizawa T, Sharpe J, Ohno T, Abe S, Nishimura A, Cartron G, Morschhauser F, Fegan C, Salles G. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016 Jan 28;127(4):411-9. doi: 10.1182/blood-2015-08-664086. Epub 2015 Nov 5. PubMed PMID: 26542378; PubMed Central PMCID: PMC4731845.

4: Robak P, Smolewski P, Robak T. Emerging immunological drugs for chronic lymphocytic leukemia. Expert Opin Emerg Drugs. 2015 Sep;20(3):423-47. doi: 10.1517/14728214.2015.1046432. Epub 2015 Jul 11. Review. PubMed PMID: 26153226.

5: Burger JA. Bruton's tyrosine kinase (BTK) inhibitors in clinical trials. Curr Hematol Malig Rep. 2014 Mar;9(1):44-9. doi: 10.1007/s11899-013-0188-8. Review. PubMed PMID: 24357428.

6: Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013 Aug 19;6:59. doi: 10.1186/1756-8722-6-59. Review. PubMed PMID: 23958373; PubMed Central PMCID: PMC3751776.