KR102753323B1 - 엘라미프레티드의 합성에 유용한 결정질 디펩티드 - Google Patents
엘라미프레티드의 합성에 유용한 결정질 디펩티드 Download PDFInfo
- Publication number
- KR102753323B1 KR102753323B1 KR1020207031595A KR20207031595A KR102753323B1 KR 102753323 B1 KR102753323 B1 KR 102753323B1 KR 1020207031595 A KR1020207031595 A KR 1020207031595A KR 20207031595 A KR20207031595 A KR 20207031595A KR 102753323 B1 KR102753323 B1 KR 102753323B1
- Authority
- KR
- South Korea
- Prior art keywords
- crystalline form
- compound
- elamipretide
- crystalline
- synthesis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- SFVLTCAESLKEHH-WKAQUBQDSA-N (2s)-6-amino-2-[[(2s)-2-[[(2r)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-n-[(2s)-1-amino-1-oxo-3-phenylpropan-2-yl]hexanamide Chemical compound CC1=CC(O)=CC(C)=C1C[C@H](NC(=O)[C@H](N)CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N)=O)CC1=CC=CC=C1 SFVLTCAESLKEHH-WKAQUBQDSA-N 0.000 title description 11
- 108010033284 arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide Proteins 0.000 title description 10
- 229950009298 elamipretide Drugs 0.000 title description 10
- 230000015572 biosynthetic process Effects 0.000 title description 7
- 238000003786 synthesis reaction Methods 0.000 title description 6
- 108010016626 Dipeptides Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 34
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 32
- 239000013078 crystal Substances 0.000 abstract description 9
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004065 mitochondrial dysfunction Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- WJJGAKCAAJOICV-JTQLQIEISA-N (2s)-2-(dimethylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound CN(C)[C@H](C(O)=O)CC1=CC=C(O)C=C1 WJJGAKCAAJOICV-JTQLQIEISA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
- C07K5/06095—Arg-amino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1019—Tetrapeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2299/00—Coordinates from 3D structures of peptides, e.g. proteins or enzymes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020257000322A KR20250010134A (ko) | 2018-04-02 | 2019-03-28 | 엘라미프레티드의 합성에 유용한 결정질 디펩티드 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862651430P | 2018-04-02 | 2018-04-02 | |
| US62/651,430 | 2018-04-02 | ||
| PCT/US2019/024617 WO2019195080A1 (en) | 2018-04-02 | 2019-03-28 | Crystalline dipeptides useful in the synthesis of elamipretide |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020257000322A Division KR20250010134A (ko) | 2018-04-02 | 2019-03-28 | 엘라미프레티드의 합성에 유용한 결정질 디펩티드 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20210005042A KR20210005042A (ko) | 2021-01-13 |
| KR102753323B1 true KR102753323B1 (ko) | 2025-01-09 |
Family
ID=68101313
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020207031595A Active KR102753323B1 (ko) | 2018-04-02 | 2019-03-28 | 엘라미프레티드의 합성에 유용한 결정질 디펩티드 |
| KR1020257000322A Pending KR20250010134A (ko) | 2018-04-02 | 2019-03-28 | 엘라미프레티드의 합성에 유용한 결정질 디펩티드 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020257000322A Pending KR20250010134A (ko) | 2018-04-02 | 2019-03-28 | 엘라미프레티드의 합성에 유용한 결정질 디펩티드 |
Country Status (13)
| Country | Link |
|---|---|
| US (4) | US10975118B2 (https=) |
| EP (2) | EP3774844B1 (https=) |
| JP (2) | JP7350007B2 (https=) |
| KR (2) | KR102753323B1 (https=) |
| CN (2) | CN112292388B (https=) |
| AU (1) | AU2019249121B2 (https=) |
| CA (2) | CA3280578A1 (https=) |
| DK (1) | DK3774844T3 (https=) |
| ES (1) | ES2941266T3 (https=) |
| FI (1) | FI3774844T3 (https=) |
| IL (2) | IL315355A (https=) |
| PT (1) | PT3774844T (https=) |
| WO (1) | WO2019195080A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115160402A (zh) * | 2016-03-11 | 2022-10-11 | 隐形生物治疗公司 | 结晶盐形式 |
| PT3774844T (pt) | 2018-04-02 | 2023-03-28 | Stealth Biotherapeutics Inc | Dipeptídeos cristalinos úteis na síntese de elamipretida |
| CN117881411A (zh) | 2021-06-01 | 2024-04-12 | 艾迪雅生物有限责任公司 | 用于眼部药物的延长释放药物递送系统和使用方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016144905A1 (en) | 2015-03-06 | 2016-09-15 | Stealth Biotherapeutics Corp | Processes for preparing pharmaceutically relevant peptides |
| WO2017156403A1 (en) | 2016-03-11 | 2017-09-14 | Stealth Biotherapeutics | Crystalline salt forms |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4711166B2 (ja) * | 2004-08-03 | 2011-06-29 | 株式会社 液晶先端技術開発センター | 結晶化装置、および結晶化方法 |
| CA3022250A1 (en) * | 2012-12-12 | 2014-06-12 | Ariad Pharmaceuticals, Inc. | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| CN104945453B (zh) * | 2014-03-28 | 2018-06-26 | 江苏天士力帝益药业有限公司 | 吡唑衍生物的多晶型物 |
| WO2016001042A1 (en) | 2014-06-30 | 2016-01-07 | Flamma S.P.A. | Process for the production of d-arginyl-2,6-dimethyl-l-tyrosyl-l-lysyl-l-phenylalaninamide |
| CA3254279A1 (en) * | 2015-06-03 | 2025-03-18 | Triastek, Inc. | PHARMACEUTICAL FORMS AND RELATED USES |
| CN110087667A (zh) | 2016-08-16 | 2019-08-02 | 隐形生物治疗公司 | Elamipretide的基于N-羧基酸酐的规模合成 |
| CN110914287A (zh) * | 2017-04-05 | 2020-03-24 | 隐形生物治疗公司 | Boc-d-arg-dmt-lys-(boc)-phe-nh2的结晶盐形式 |
| PT3774844T (pt) | 2018-04-02 | 2023-03-28 | Stealth Biotherapeutics Inc | Dipeptídeos cristalinos úteis na síntese de elamipretida |
-
2019
- 2019-03-28 PT PT197814320T patent/PT3774844T/pt unknown
- 2019-03-28 CA CA3280578A patent/CA3280578A1/en active Pending
- 2019-03-28 WO PCT/US2019/024617 patent/WO2019195080A1/en not_active Ceased
- 2019-03-28 JP JP2020554100A patent/JP7350007B2/ja active Active
- 2019-03-28 EP EP19781432.0A patent/EP3774844B1/en active Active
- 2019-03-28 ES ES19781432T patent/ES2941266T3/es active Active
- 2019-03-28 CN CN201980037029.8A patent/CN112292388B/zh active Active
- 2019-03-28 EP EP23156906.2A patent/EP4219523A3/en active Pending
- 2019-03-28 DK DK19781432.0T patent/DK3774844T3/da active
- 2019-03-28 CN CN202410219985.0A patent/CN118206614A/zh active Pending
- 2019-03-28 AU AU2019249121A patent/AU2019249121B2/en active Active
- 2019-03-28 IL IL315355A patent/IL315355A/en unknown
- 2019-03-28 FI FIEP19781432.0T patent/FI3774844T3/fi active
- 2019-03-28 KR KR1020207031595A patent/KR102753323B1/ko active Active
- 2019-03-28 IL IL277718A patent/IL277718B2/en unknown
- 2019-03-28 CA CA3095869A patent/CA3095869C/en active Active
- 2019-03-28 US US16/485,369 patent/US10975118B2/en active Active
- 2019-03-28 KR KR1020257000322A patent/KR20250010134A/ko active Pending
-
2021
- 2021-04-07 US US17/224,353 patent/US11560404B2/en active Active
-
2022
- 2022-12-21 US US18/086,203 patent/US12018094B2/en active Active
-
2023
- 2023-09-12 JP JP2023147376A patent/JP7663642B2/ja active Active
-
2024
- 2024-05-15 US US18/665,100 patent/US20250122238A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016144905A1 (en) | 2015-03-06 | 2016-09-15 | Stealth Biotherapeutics Corp | Processes for preparing pharmaceutically relevant peptides |
| WO2017156403A1 (en) | 2016-03-11 | 2017-09-14 | Stealth Biotherapeutics | Crystalline salt forms |
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