WO2010028122A1 - Process for making bivalirudin - Google Patents
Process for making bivalirudin Download PDFInfo
- Publication number
- WO2010028122A1 WO2010028122A1 PCT/US2009/055853 US2009055853W WO2010028122A1 WO 2010028122 A1 WO2010028122 A1 WO 2010028122A1 US 2009055853 W US2009055853 W US 2009055853W WO 2010028122 A1 WO2010028122 A1 WO 2010028122A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tbu
- product
- segment
- hcl
- organic solvent
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/815—Protease inhibitors from leeches, e.g. hirudin, eglin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
Definitions
- the present invention relates to the efficient commercial synthesis for the making of bivalirudin, a peptide. It is well known that bivalirudin is indicated to reduce the risk of acute ischemic complications, and is an anticoagulant and acts as a direct thrombin inhibitor. The process substantially comprises the syntheses of various fragments of the polypeptide and the coupling of the fragments to produce bivalirudin.
- Thrombin inhibitors are synthesized by various techniques which are well known in the art. These include enzymatic cleavage of natural or recombinant hirudin, recombinant DNA techniques, solid-phase peptide synthesis, solution-phase peptide synthesis, organic chemical synthesis techniques, or a combination of these techniques . [0004] The following references disclose various techniques for producing thrombin inhibitors. (1) US 5196404 (2) US 5240913
- the present invention provides for an efficient process of making Bivalirudin in solution that is high in yield and scalable for commercial production.
- the process comprises the stepwise synthesis of amino acid segments Sl, S2, S3, ⁇ 4, and the coupling together of these segments to produce Bivalirudin.
- the process of the present invention provides for the making of
- Bivalirudin that is in high yield and of high purity compared to the solid-phase peptide synthesis method.
- the appended claims are directed to process for making Bivalirudin and for making various novel intermediates . Recitation within these claims to first organic solvent, second organic solvent, and so forth, is meant to indicate that the organic solvents may be different or the same within the same claimed process; and that recitation of the same term for the organic solvent from one claimed process to another different claimed process does not necessarily indicate that the solvents are the same.
- Figure 1 depicts the synthesis of the peptide Segment 1 (Sl) as disclosed in Examples 1, 2 and 3.
- Figure 2 depicts the synthesis of the peptide Segment 2 (S2) as disclosed in Examples 4 and 5.
- Figure 3 depicts the synthesis of the peptide Segment 3 (S3) as disclosed in Examples 6, 7 and 8.
- Figure 4 depicts the synthesis of the peptide Segment 4 (S4) as disclosed in Examples 9 and 10.
- Figure 5 depicts the synthesis of the
- S2M1 (Ml of segment 2) - FmocAsn (Trt) GIyOtBu
- S2M2 (M2 of segment 2) - Asn (Trt) GIyOtBu
- S2M3 (M3 of segment 2) - FmocGlyAsn (Trt) GIyOtBu [00023]
- S2M4 (M4 of segment 2 ⁇ - GlyGlyAsn (Trt) GIyOtBu [00024]
- S2M5 (M5 of segment 2) FmocGlyGlyGlyGlyAsn (Trt) GIyOtBu [00025]
- S2 (Segment 2) - FmocGlyGlyGlyGlyAsnGlyOH [00026]
- S3M1 (Ml of segment 3) - BocIleProOBn [00027]
- S3M2 (M2 of segment 3) - HCl IleProOBn [00028]
- S3M3 (M3 of segment 3) - FmocGlu (tBu) IleProOBn [00029]
- S3M4 (M4 of segment 3) - GIu (t
- S3M6 (M6 of segment 3) GIu (tBu) GIu (tBu) IleProOBn
- S3M7 (M7 of segment 3) FmocPheGlu(tBu ⁇ Glu ⁇ tBu) IleProOBn
- EA - Ethyl acetate [00056] DIC - N, N' -Diisopropylcarbodiimide [00057] DCM - Di chloromethane [00058] DMF - N, N-Dimethyl formamide [00059] DMSO - Dimethyl sulfoxide [00060] DBU - 1, 8-Diazobicyclo [5, 4 , 0] undec-7-ene [00061] DEA - Diethanolamine [00062] DIEA - N,N-Diisoproylethylamine [00063] MTBE - Methyl tert-butyl ether [00064] NMM - N-Methylmorpholine
- the reaction mixture was allowed to assume room, temperature for another 3 h.
- the reaction mixture was neutralized with IN HCl ⁇ aq. ⁇ , followed by concentrated to about 3/5 volume.
- the product in aqueous layer was precipitated out by adjusting pH to about 3 with IN HCl (aq.) .
- the precipitated product was separated by filtration and washed with water (2 X 10 L) . Yield: 1.12 Kg
- Example 1 The compounds from Example 1 (1.00 Kg) and Example 2 (1.32 kg) were dissolved in DMF (5 L) and HOBt (0.41 kg) was added. NMM (0.41 L) and EDCI (0.63 kg) were added and the reaction was stirred for 2 h.
- the reaction mixture was diluted by DCM (10 L), washed with water (10 L) and concentrated to about 1/5 volume.
- the concentrated mixture was added into methyl-t-butyl ether (MTBE, 40 L) for intermediate precipitation.
- the precipitated intermediate was separated by filtration and washed with MTBE (2 X 20 L) to get intermediate (S1M5) .
- the intermediate (S1M5) was dissolved in MeOH (6 L) followed by added into mixed solvents of MeOH (6 L) and IN NaOH (aq. 5.5 L) .
- the reaction was allowed stirring for 5 h, then neutralized with HCl ⁇ aq. ⁇ , followed by concentrated.
- the concentrated residue was extracted with DCM (15 L) after pH adjusted to about 3.
- the organic layer was concentrated and added into MTBE (40 L) for product precipitation.
- the precipitated product was separated by filtration and washed with MTBE (2 X 20 L) . Yield: 1.48 kg
- the product was precipitated out by solvent replacement with n-Heptane and adding MTBE (20 L) .
- the precipitated product was separated by filtration, washed with MTBE
- DCM solution of intermediate (S3M4, about 7 L) DCM solution of intermediate (S3M4, about 7 L) .
- the DCM solution of intermediate ( ⁇ 3M4) was mixed with protected amino acid FmocGlu (tBu) OH (0.86 kg) and HOBt (0.28 kg) .
- EDCI (0.60 kg) was added and was allowed to react for 1 h to give DCM solution of intermediate (S3M5, about 7 L) .
- DBU (0.47 L) was added into the DCM solution of intermediate (S3M5) and was allowed react for 1 h.
- the reaction mixture was washed with water (total 9 L) and 5% Na2CO3 (aq. 3 L) to give DCM solution of intermediate (S3M6, about 7 L) .
- Example 8 The compounds from Example 8 (1.00 Kg ⁇ and Example 5 (0.70 kg) were dissolved in DMSO (7 L) and HOBt (0.16 kg) was added. EDCI (0.48 kg ⁇ was added and the reaction mixture was allowed stirring for another 1 h, then Piperidine (1 L) was added and the reaction was allowed stirring for another 2 h. The product was precipitated out by adding water (35 L) . The precipitated product was separated by filtration and washed with water ⁇ 2 X 10 L) and MTBE (3 X 10 L) . Yield: 1.26kg
- Example 12 The compounds from Example 12 (1.00 Kg) and Example 10 ⁇ 0.42 kg) were dissolved in DMSO (5.8 L) and HOBt (0.08 kg) was added. EDCI (0.15 kg) was added and the reaction mixture was allowed stirring continued for another 1 h.
- the intermediate (M5) was precipitated out by adding water (24 L) and was separated by filtration and washed with water (2 X 6 L) .
- the precipitated intermediate (M5) was dissolved in mixed solvents of water (0.08 L), TIS (0.33 L) and TFA (7.92 L) and the mixture was allowed to react for 1 h.
- the product was precipitated out by slowly adding MTBE (29.2 L) and was separated by filtration, washed with MTBE (2 X 8.3 L) and THF (2 X 8.3 L) . Yield: 1.12 kg
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Analytical Chemistry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Zoology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2009288027A AU2009288027B2 (en) | 2008-09-03 | 2009-09-03 | Process for making Bivalirudin |
CA2736126A CA2736126C (en) | 2008-09-03 | 2009-09-03 | Process for making bivalirudin |
EP09812204.7A EP2349307B1 (en) | 2008-09-03 | 2009-09-03 | Process for making bivalirudin |
JP2011526190A JP5788321B2 (en) | 2008-09-03 | 2009-09-03 | Bivalirudine production method |
CN2009801379027A CN102164609A (en) | 2008-09-03 | 2009-09-03 | Process for making bivalirudin |
IL211555A IL211555A (en) | 2008-09-03 | 2011-03-03 | Process for making bivalirudin |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US19092808P | 2008-09-03 | 2008-09-03 | |
US61/190,928 | 2008-09-03 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2010028122A1 true WO2010028122A1 (en) | 2010-03-11 |
WO2010028122A8 WO2010028122A8 (en) | 2014-11-13 |
Family
ID=41726391
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2009/055867 WO2010028131A1 (en) | 2008-09-03 | 2009-09-03 | Process for the preparation of pramlintide |
PCT/US2009/055853 WO2010028122A1 (en) | 2008-09-03 | 2009-09-03 | Process for making bivalirudin |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2009/055867 WO2010028131A1 (en) | 2008-09-03 | 2009-09-03 | Process for the preparation of pramlintide |
Country Status (11)
Country | Link |
---|---|
US (2) | US8252896B2 (en) |
EP (2) | EP2349307B1 (en) |
JP (2) | JP2012502045A (en) |
KR (2) | KR20110056536A (en) |
CN (2) | CN102164609A (en) |
AR (2) | AR073360A1 (en) |
AU (2) | AU2009288036A1 (en) |
CA (2) | CA2736126C (en) |
IL (2) | IL211556A0 (en) |
TW (2) | TW201024316A (en) |
WO (2) | WO2010028131A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010075983A1 (en) * | 2008-12-29 | 2010-07-08 | Lonza Braine Sa | Process for the production of bivalirudin |
WO2013042129A1 (en) * | 2011-09-23 | 2013-03-28 | Natco Pharma Limited | Improved process for preparation of bivalirudin |
USRE46830E1 (en) | 2004-10-19 | 2018-05-08 | Polypeptide Laboratories Holding (Ppl) Ab | Method for solid phase peptide synthesis |
US10087221B2 (en) | 2013-03-21 | 2018-10-02 | Sanofi-Aventis Deutschland Gmbh | Synthesis of hydantoin containing peptide products |
US10450343B2 (en) | 2013-03-21 | 2019-10-22 | Sanofi-Aventis Deutschland Gmbh | Synthesis of cyclic imide containing peptide products |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2008271608A1 (en) * | 2007-06-29 | 2009-01-08 | Lonza Ag | Process for the production of pramlintide |
CN102180943A (en) * | 2010-12-16 | 2011-09-14 | 深圳市健元医药科技有限公司 | Production process of polypeptide medicament for assisting to reduce blood sugar |
WO2014032257A1 (en) * | 2012-08-30 | 2014-03-06 | 深圳翰宇药业股份有限公司 | Method for preparing bivalirudin |
CN104861045A (en) * | 2014-02-20 | 2015-08-26 | 复旦大学 | Cyclopeptide compound GG6F and preparation method thereof |
ES2939036T3 (en) * | 2019-01-24 | 2023-04-18 | Dsm Ip Assets Bv | Peptide precipitation method |
CN111499719B (en) * | 2020-03-19 | 2022-04-08 | 杭州固拓生物科技有限公司 | Method for synthesizing pramlintide |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5196404A (en) | 1989-08-18 | 1993-03-23 | Biogen, Inc. | Inhibitors of thrombin |
US5240913A (en) | 1989-08-18 | 1993-08-31 | Biogen, Inc. | Inhibitors of thrombin |
WO1998050563A1 (en) | 1997-05-01 | 1998-11-12 | Ppl Therapeutics (Scotland) Ltd. | Methods of production of an amidated peptide through the use of a fusion protein |
US20070093423A1 (en) | 2005-09-14 | 2007-04-26 | Avi Tovi | Process for production of Bivalirudin |
US20070213505A1 (en) * | 2006-03-08 | 2007-09-13 | David Epstein | Solution Synthesis of Peptide Cell Growth Stimulators |
US20080051558A1 (en) | 2006-03-10 | 2008-02-28 | Yiming Zhou | Method of preparing bivalirudin |
US20080287648A1 (en) | 2004-10-19 | 2008-11-20 | Lonza Ag | Method for Solid Phase Peptide Synthesis |
US20080287650A1 (en) | 2007-03-01 | 2008-11-20 | Avi Tovi | High purity peptides |
US20090062511A1 (en) | 2007-09-05 | 2009-03-05 | Raghavendracharyulu Venkata Palle | Process for the preparation of bivalirudin and its pharmaceutical compositions |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU222249B1 (en) | 1991-03-08 | 2003-05-28 | Amylin Pharmaceuticals Inc. | Process for producing amyline antagonistic peptide derivatives and pharmaceutical preparatives containing them |
WO1992015317A1 (en) | 1991-03-08 | 1992-09-17 | Amylin Pharmaceuticals, Inc. | Synthetic preparation of amylin and amylin analogues |
US6821954B2 (en) * | 1997-09-18 | 2004-11-23 | Auckland Uniservices Limited | Compounds and uses thereof in treating bone disorders |
WO1999048513A1 (en) * | 1998-03-23 | 1999-09-30 | Trimeris, Inc. | Methods and compositions for peptide synthesis |
TW200637872A (en) * | 2004-10-26 | 2006-11-01 | Lonza Ag | Thiol group protection and cyclization in solid-phase peptide synthesis |
AU2008271608A1 (en) * | 2007-06-29 | 2009-01-08 | Lonza Ag | Process for the production of pramlintide |
CA2744627C (en) * | 2008-12-29 | 2016-08-16 | Lonza Braine Sa | Process for the production of bivalirudin |
-
2009
- 2009-09-03 AU AU2009288036A patent/AU2009288036A1/en not_active Abandoned
- 2009-09-03 WO PCT/US2009/055867 patent/WO2010028131A1/en active Application Filing
- 2009-09-03 AR ARP090103393A patent/AR073360A1/en unknown
- 2009-09-03 CN CN2009801379027A patent/CN102164609A/en active Pending
- 2009-09-03 EP EP09812204.7A patent/EP2349307B1/en not_active Not-in-force
- 2009-09-03 CA CA2736126A patent/CA2736126C/en not_active Expired - Fee Related
- 2009-09-03 AU AU2009288027A patent/AU2009288027B2/en not_active Ceased
- 2009-09-03 KR KR1020117007671A patent/KR20110056536A/en not_active Application Discontinuation
- 2009-09-03 CA CA2736113A patent/CA2736113A1/en not_active Abandoned
- 2009-09-03 AR ARP090103394A patent/AR073544A1/en unknown
- 2009-09-03 EP EP09812207A patent/EP2334314A4/en not_active Withdrawn
- 2009-09-03 US US12/553,482 patent/US8252896B2/en active Active
- 2009-09-03 TW TW098129667A patent/TW201024316A/en unknown
- 2009-09-03 JP JP2011526194A patent/JP2012502045A/en active Pending
- 2009-09-03 WO PCT/US2009/055853 patent/WO2010028122A1/en active Application Filing
- 2009-09-03 JP JP2011526190A patent/JP5788321B2/en not_active Expired - Fee Related
- 2009-09-03 CN CN2009801378950A patent/CN102164608A/en active Pending
- 2009-09-03 KR KR1020117007669A patent/KR101634830B1/en active IP Right Grant
- 2009-09-03 US US12/553,567 patent/US20100081788A1/en not_active Abandoned
- 2009-09-03 TW TW098129702A patent/TWI395752B/en not_active IP Right Cessation
-
2011
- 2011-03-03 IL IL211556A patent/IL211556A0/en unknown
- 2011-03-03 IL IL211555A patent/IL211555A/en active IP Right Grant
Patent Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5691311A (en) | 1989-08-18 | 1997-11-25 | Biogen, Inc. | Methods for coating invasive devices with inhibitors of thrombin |
US5196404A (en) | 1989-08-18 | 1993-03-23 | Biogen, Inc. | Inhibitors of thrombin |
US5425936A (en) | 1989-08-18 | 1995-06-20 | Biogen, Inc. | Inhibitors of thrombin |
US5433940A (en) | 1989-08-18 | 1995-07-18 | Biogen, Inc. | Inhibitors of thrombin |
US5514409A (en) | 1989-08-18 | 1996-05-07 | Biogen, Inc. | Methods for coating invasive devices with inhibitors of thrombin |
US5196404B1 (en) | 1989-08-18 | 1996-09-10 | Biogen Inc | Inhibitors of thrombin |
US5240913A (en) | 1989-08-18 | 1993-08-31 | Biogen, Inc. | Inhibitors of thrombin |
WO1998050563A1 (en) | 1997-05-01 | 1998-11-12 | Ppl Therapeutics (Scotland) Ltd. | Methods of production of an amidated peptide through the use of a fusion protein |
US20080287648A1 (en) | 2004-10-19 | 2008-11-20 | Lonza Ag | Method for Solid Phase Peptide Synthesis |
US20070093423A1 (en) | 2005-09-14 | 2007-04-26 | Avi Tovi | Process for production of Bivalirudin |
US20070213505A1 (en) * | 2006-03-08 | 2007-09-13 | David Epstein | Solution Synthesis of Peptide Cell Growth Stimulators |
US20080051558A1 (en) | 2006-03-10 | 2008-02-28 | Yiming Zhou | Method of preparing bivalirudin |
US20080287650A1 (en) | 2007-03-01 | 2008-11-20 | Avi Tovi | High purity peptides |
US20090062511A1 (en) | 2007-09-05 | 2009-03-05 | Raghavendracharyulu Venkata Palle | Process for the preparation of bivalirudin and its pharmaceutical compositions |
Non-Patent Citations (1)
Title |
---|
See also references of EP2349307A1 |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
USRE46830E1 (en) | 2004-10-19 | 2018-05-08 | Polypeptide Laboratories Holding (Ppl) Ab | Method for solid phase peptide synthesis |
WO2010075983A1 (en) * | 2008-12-29 | 2010-07-08 | Lonza Braine Sa | Process for the production of bivalirudin |
JP2012514015A (en) * | 2008-12-29 | 2012-06-21 | ロンザ・ブレーヌ・エスエー | Bivalirudine production method |
US8921517B2 (en) | 2008-12-29 | 2014-12-30 | Lonza Braine Sa | Process for the production of bivalirudin |
WO2013042129A1 (en) * | 2011-09-23 | 2013-03-28 | Natco Pharma Limited | Improved process for preparation of bivalirudin |
US10087221B2 (en) | 2013-03-21 | 2018-10-02 | Sanofi-Aventis Deutschland Gmbh | Synthesis of hydantoin containing peptide products |
US10450343B2 (en) | 2013-03-21 | 2019-10-22 | Sanofi-Aventis Deutschland Gmbh | Synthesis of cyclic imide containing peptide products |
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