CL2016002513A1 - Método para preparar amg 416 - Google Patents
Método para preparar amg 416Info
- Publication number
- CL2016002513A1 CL2016002513A1 CL2016002513A CL2016002513A CL2016002513A1 CL 2016002513 A1 CL2016002513 A1 CL 2016002513A1 CL 2016002513 A CL2016002513 A CL 2016002513A CL 2016002513 A CL2016002513 A CL 2016002513A CL 2016002513 A1 CL2016002513 A1 CL 2016002513A1
- Authority
- CL
- Chile
- Prior art keywords
- arg
- pbf
- amg
- additional embodiments
- spy
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract 12
- ANIAZGVDEUQPRI-ZJQCGQFWSA-N etelcalcetide Chemical compound NC(N)=NCCC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCCN=C(N)N)NC(=O)[C@@H](CCCN=C(N)N)NC(=O)[C@@H](CCCN=C(N)N)NC(=O)[C@@H](C)NC(=O)[C@@H](CSSC[C@H](N)C(O)=O)NC(C)=O ANIAZGVDEUQPRI-ZJQCGQFWSA-N 0.000 title abstract 8
- 229950006502 etelcalcetide Drugs 0.000 title abstract 8
- 108091022127 etelcalcetide hydrochloride Proteins 0.000 title abstract 8
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 abstract 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 abstract 5
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 5
- 239000011347 resin Substances 0.000 abstract 4
- 229920005989 resin Polymers 0.000 abstract 4
- 239000000243 solution Substances 0.000 abstract 4
- 235000009518 sodium iodide Nutrition 0.000 abstract 3
- 239000002904 solvent Substances 0.000 abstract 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 3
- CVFXPOKENLGCID-QGZVFWFLSA-N (2r)-5-[[amino-[(2,2,4,6,7-pentamethyl-3h-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC1=C(S(=O)(=O)NC(N)=NCCC[C@@H](NC(=O)OC(C)(C)C)C(O)=O)C(C)=C2CC(C)(C)OC2=C1C CVFXPOKENLGCID-QGZVFWFLSA-N 0.000 abstract 2
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 abstract 2
- 239000007864 aqueous solution Substances 0.000 abstract 2
- GVIXTVCDNCXXSH-CQSZACIVSA-N (2r)-5-[[amino-[(2,2,4,6,7-pentamethyl-3h-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-2-azaniumylpentanoate Chemical compound OC(=O)[C@H](N)CCCN=C(N)NS(=O)(=O)C1=C(C)C(C)=C2OC(C)(C)CC2=C1C GVIXTVCDNCXXSH-CQSZACIVSA-N 0.000 abstract 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 abstract 1
- 125000000028 D-cysteine group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C(S[H])([H])[H] 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 1
- 230000004913 activation Effects 0.000 abstract 1
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 abstract 1
- 238000010533 azeotropic distillation Methods 0.000 abstract 1
- 238000003776 cleavage reaction Methods 0.000 abstract 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 abstract 1
- -1 for example Substances 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 abstract 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 abstract 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 230000007017 scission Effects 0.000 abstract 1
- 239000007787 solid Substances 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 abstract 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
-
- 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
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/20—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of PTH
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Glass Compositions (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
<p>A la vista de los problemas descritos anteriormente, es un objetivo de la divulgación proporcionar un método para preparar AMG 416, o una sal farmacéuticamente aceptable del mismo, entre otras cosas. En un primer aspecto, se proporciona un método para preparar AMG 416, comprendiendo el método: proporcionar un péptido unido a resina que tenga una estructura seleccionada del grupo que consiste en Fmoc-D-Cys (Trt) -D-Ala-D - Arg (Pbf) -D-Arg (Pbf) -D-Arg (Pbf) -D-AlaD-Arg (Pbf) - [Resina] (SEQ ID NO:2) y Ac-D-Cys (Trt) -D-Ala-D-Arg (Pbf) -D-Arg (Pbf) -D-Arg (Pbf) -D-Ala-D-Arg (Pbf) - [Resina] (SEQ ID NO:3); escindir el péptido del soporte sólido; y activar la cadena lateral del residuo de D-Cys del péptido escindido. 3 En una o más realizaciones relacionadas con el primer aspecto, las etapas de escisión y activación se producen en el mismo reactor. En una o más realizaciones adicionales, el péptido unido a resina se pone en contacto con una solución compuesta de agua, ácido trifluoroacético, triisopropilsilano y dipiridildisulfuro. En un segundo aspecto, se proporciona un método para preparar AMG 416, comprendiendo el método: proporcionar un péptido que tiene una es 4 solución acuosa de TFA al 0,1% (solución de ácido trifluoroacético), y purificando el derivado de AMG 416 SPy por HPLC. En algunas realizaciones relacionadas con el tercer aspecto, el método comprende además la destilación azeotrópica del intermediario AMG 416 SPy, para efectuar de ese modo un intercambio de disolvente para producir una solución del AMG 416 SPy en el nuevo disolvente, por ejemplo, agua y alcohol isopropílico. En algunas realizaciones adicionales relacionadas con el tercer aspecto, el método comprende adicionalmente poner en contacto la solución de alcohol isopropílico-agua del AMG 416 SPy, en algunas realizaciones en forma de su sal de trifluoroacetato, con una solución acuosa que está compuesta de L-Cys . En un cuarto aspecto, se entrega un método para preparar H-D-Arg (Pbf) -OH, es decir, un material de partida adecuado para algunos de los métodos de síntesis proporcionados en este documento. En algunas realizaciones relacionadas con el cuarto aspecto, el método comprende convertir Boc-D-Arg-OH en Boc-D-Arg (Pbf) -OH en presencia de NaI (yoduro de sodio). En algunas realizaciones adicionales, el yoduro de sodio está presente en una concentración de aproximadamente 5% molar. En algunas realizaciones adicionales relacionadas con el cuarto aspecto, el método comprende además convertir Boc-D-Arg (Pbf) -OH en D-Arg (Pbf) -OH, y cristalizar el D-Arg (Pbf) -OH en un sistema solvente IPA/agua. Las realizaciones adicionales de los métodos descritos en este documento serán evidentes a partir de la siguiente descripción, ejemplos y reivindicaciones. Como puede apreciarse a partir de la descripción precedente y siguiente, cada una de las características descritas aquí, y cada combinación de dos o más de tales características, está incluida dentro del alcance de la presente divulgación, siempre que las características incluidas en tal combinación no sean mutuamente inconsistentes. Además, cualquier característica o combinación de 5 características se puede específicamente excluir de cualquier realización de la presente invención.</p>
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461974899P | 2014-04-03 | 2014-04-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CL2016002513A1 true CL2016002513A1 (es) | 2018-03-23 |
Family
ID=54241346
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CL2016002513A CL2016002513A1 (es) | 2014-04-03 | 2016-10-03 | Método para preparar amg 416 |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US10407464B2 (es) |
| EP (3) | EP4219526A3 (es) |
| JP (1) | JP6710158B2 (es) |
| KR (1) | KR102397271B1 (es) |
| CN (1) | CN106795201A (es) |
| AU (1) | AU2015240527B2 (es) |
| BR (1) | BR112016022868A2 (es) |
| CA (1) | CA2944194C (es) |
| CL (1) | CL2016002513A1 (es) |
| CY (1) | CY1123100T1 (es) |
| DK (1) | DK3126373T3 (es) |
| EA (1) | EA032597B1 (es) |
| ES (2) | ES2786225T3 (es) |
| HR (1) | HRP20200527T1 (es) |
| HU (1) | HUE048489T2 (es) |
| IL (1) | IL248059B2 (es) |
| LT (1) | LT3126373T (es) |
| MA (2) | MA39628B1 (es) |
| ME (1) | ME03781B (es) |
| MX (1) | MX2016012965A (es) |
| PL (1) | PL3126373T3 (es) |
| PT (1) | PT3126373T (es) |
| RS (1) | RS60187B1 (es) |
| SG (1) | SG11201608176VA (es) |
| SI (1) | SI3126373T1 (es) |
| WO (1) | WO2015154031A1 (es) |
| ZA (1) | ZA201606844B (es) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3246017B1 (en) * | 2013-06-28 | 2021-03-24 | Amgen Inc. | Stable liquid formulation of amg 416 hcl (etelcalcetide) |
| EP4219526A3 (en) | 2014-04-03 | 2023-08-30 | Amgen, Inc. | Method for preparing amg 416 |
| CN106928321B (zh) * | 2015-12-31 | 2019-07-26 | 深圳翰宇药业股份有限公司 | 一种合成Etelcalcetide的方法 |
| CN106928320B (zh) * | 2015-12-31 | 2021-01-15 | 深圳翰宇药业股份有限公司 | 一种合成Etelcalcetide的方法 |
| EP3433267B1 (en) * | 2016-03-23 | 2022-08-24 | Bachem Holding AG | Method for preparing glucagon-like peptides |
| US10858390B2 (en) | 2016-09-02 | 2020-12-08 | Cem Corporation | Use of excess carbodiimide for peptide synthesis at elevated temperatures |
| CN108101959B (zh) * | 2016-11-24 | 2021-07-09 | 四川科伦药物研究院有限公司 | 一种制备高纯度多肽或其类似物的方法 |
| CN106928171B (zh) * | 2017-05-03 | 2019-08-13 | 成都郑源生化科技有限公司 | Fmoc-Arg（Pbf）-OH的合成方法 |
| TW201915009A (zh) * | 2017-10-03 | 2019-04-16 | 中化合成生技股份有限公司 | 合成依特卡肽（Ｅｔｅｌｃａｌｃｅｔｉｄｅ）或其鹽類之方法 |
| CN110498835B (zh) * | 2018-05-17 | 2021-06-08 | 深圳翰宇药业股份有限公司 | 一种合成etelcalcetide的方法 |
| CN109280078B (zh) * | 2018-10-30 | 2019-06-25 | 成都诺和晟泰生物科技有限公司 | 一种制备维拉卡肽的方法 |
| CN112062811B (zh) * | 2019-06-10 | 2022-03-25 | 深圳翰宇药业股份有限公司 | 一种维拉卡肽的合成方法 |
| US20220298206A1 (en) * | 2019-08-26 | 2022-09-22 | Auro Peptides Ltd | An improved process for the preparation of Etelcalcetide Hydrochloride |
| EP3875466A1 (en) * | 2020-03-05 | 2021-09-08 | Fresenius Kabi iPSUM S.r.l. | Process for the synthesis of etelcalcetide |
| TW202210498A (zh) | 2020-06-03 | 2022-03-16 | 日商中外製藥股份有限公司 | 高難度序列之有效率的胜肽縮合法 |
| CN111925415A (zh) * | 2020-08-10 | 2020-11-13 | 海南中和药业股份有限公司 | 一种维拉卡肽杂质的制备方法 |
| TWI792442B (zh) * | 2021-07-23 | 2023-02-11 | 建誼生技股份有限公司 | 依特卡肽鹽酸鹽之製造方法 |
| CN114524860A (zh) * | 2021-12-29 | 2022-05-24 | 深圳翰宇药业股份有限公司 | 一种Etelcalcetide的合成方法及其应用 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3941763A (en) | 1975-03-28 | 1976-03-02 | American Home Products Corporation | PGlu-D-Met-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2 and intermediates |
| EP0339695A3 (en) | 1988-04-29 | 1990-05-30 | Stichting Voor De Technische Wetenschappen | A process for preparing an antigenic or immunogenic conjugate as well as the use of such conjugates |
| SE9603465D0 (sv) | 1996-09-23 | 1996-09-23 | Astra Ab | New compounds |
| NO311807B1 (no) | 1999-03-04 | 2002-01-28 | Bionor Immuno As | HIV-peptider, antigener, vaksinepreparater, immunoassay- testsett og en metode for påvisning av antistoffer fremkalt av HIV |
| WO2009053315A1 (en) | 2007-10-27 | 2009-04-30 | F. Hoffmann-La Roche Ag | Insulinotropic peptide synthesis using solid and solution phase combination techniques |
| CN101250172B (zh) | 2008-03-07 | 2012-05-02 | 上海瀚鸿化工科技有限公司 | 精氨酸双保护制备工艺 |
| EP2427474A1 (en) | 2009-05-06 | 2012-03-14 | Mallinckrodt LLC | Solid support for fmoc-solid phase synthesis of peptide acids |
| EP2459208B1 (en) * | 2009-07-29 | 2016-09-28 | Kai Pharmaceuticals, Inc. | Therapeutic agents for reducing parathyroid hormone levels |
| EP2560491A1 (en) * | 2010-04-21 | 2013-02-27 | Signature Therapeutics, Inc. | Peripheral opioid agonists and peripheral opioid antagonists |
| US20140024592A1 (en) * | 2010-09-08 | 2014-01-23 | Howard Florey Institute Of Experimental Physiology And Medicine | Modified Relaxin Polypeptides |
| WO2013042129A1 (en) | 2011-09-23 | 2013-03-28 | Natco Pharma Limited | Improved process for preparation of bivalirudin |
| EP3246017B1 (en) | 2013-06-28 | 2021-03-24 | Amgen Inc. | Stable liquid formulation of amg 416 hcl (etelcalcetide) |
| EP4219526A3 (en) | 2014-04-03 | 2023-08-30 | Amgen, Inc. | Method for preparing amg 416 |
| CN105504012A (zh) * | 2014-09-30 | 2016-04-20 | 深圳翰宇药业股份有限公司 | 一种多肽的制备方法 |
| CN107434820A (zh) * | 2017-08-07 | 2017-12-05 | 南京工业大学 | 一种维拉卡肽的合成方法 |
-
2015
- 2015-04-03 EP EP23150870.6A patent/EP4219526A3/en active Pending
- 2015-04-03 RS RS20200448A patent/RS60187B1/sr unknown
- 2015-04-03 JP JP2016560462A patent/JP6710158B2/ja active Active
- 2015-04-03 CN CN201580029560.2A patent/CN106795201A/zh active Pending
- 2015-04-03 EA EA201692001A patent/EA032597B1/ru not_active IP Right Cessation
- 2015-04-03 DK DK15773570.5T patent/DK3126373T3/da active
- 2015-04-03 SI SI201531173T patent/SI3126373T1/sl unknown
- 2015-04-03 LT LTEP15773570.5T patent/LT3126373T/lt unknown
- 2015-04-03 BR BR112016022868-5A patent/BR112016022868A2/pt active IP Right Grant
- 2015-04-03 EP EP15773570.5A patent/EP3126373B1/en active Active
- 2015-04-03 EP EP20160369.3A patent/EP3708576B1/en active Active
- 2015-04-03 IL IL248059A patent/IL248059B2/en unknown
- 2015-04-03 AU AU2015240527A patent/AU2015240527B2/en active Active
- 2015-04-03 HU HUE15773570A patent/HUE048489T2/hu unknown
- 2015-04-03 ES ES15773570T patent/ES2786225T3/es active Active
- 2015-04-03 ME MEP-2020-83A patent/ME03781B/me unknown
- 2015-04-03 CA CA2944194A patent/CA2944194C/en active Active
- 2015-04-03 US US15/300,209 patent/US10407464B2/en active Active
- 2015-04-03 ES ES20160369T patent/ES2943671T3/es active Active
- 2015-04-03 WO PCT/US2015/024347 patent/WO2015154031A1/en active Application Filing
- 2015-04-03 KR KR1020167030590A patent/KR102397271B1/ko active IP Right Grant
- 2015-04-03 MA MA39628A patent/MA39628B1/fr unknown
- 2015-04-03 PT PT157735705T patent/PT3126373T/pt unknown
- 2015-04-03 MX MX2016012965A patent/MX2016012965A/es active IP Right Grant
- 2015-04-03 MA MA052906A patent/MA52906A/fr unknown
- 2015-04-03 SG SG11201608176VA patent/SG11201608176VA/en unknown
- 2015-04-03 PL PL15773570T patent/PL3126373T3/pl unknown
-
2016
- 2016-10-03 CL CL2016002513A patent/CL2016002513A1/es unknown
- 2016-10-05 ZA ZA2016/06844A patent/ZA201606844B/en unknown
-
2019
- 2019-08-05 US US16/532,344 patent/US11377474B2/en active Active
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2020
- 2020-04-01 HR HRP20200527TT patent/HRP20200527T1/hr unknown
- 2020-04-29 CY CY20201100391T patent/CY1123100T1/el unknown
-
2022
- 2022-06-28 US US17/852,263 patent/US20230099078A1/en not_active Abandoned
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