TWI724651B - 貝前列素-314d單水合物晶體及其製備方法 - Google Patents
貝前列素-314d單水合物晶體及其製備方法 Download PDFInfo
- Publication number
- TWI724651B TWI724651B TW108143007A TW108143007A TWI724651B TW I724651 B TWI724651 B TW I724651B TW 108143007 A TW108143007 A TW 108143007A TW 108143007 A TW108143007 A TW 108143007A TW I724651 B TWI724651 B TW I724651B
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- TW
- Taiwan
- Prior art keywords
- beraprost
- monohydrate
- crystalline
- crystal form
- following
- Prior art date
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- 150000004682 monohydrates Chemical class 0.000 title claims abstract description 118
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims abstract description 11
- 239000013078 crystal Substances 0.000 title claims description 87
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 55
- 239000002904 solvent Substances 0.000 claims description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000002244 precipitate Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 229960002890 beraprost Drugs 0.000 claims description 7
- CTPOHARTNNSRSR-APJZLKAGSA-N beraprost Chemical compound O([C@H]1C[C@@H](O)[C@@H]([C@@H]21)/C=C/[C@@H](O)C(C)CC#CC)C1=C2C=CC=C1CCCC(O)=O CTPOHARTNNSRSR-APJZLKAGSA-N 0.000 claims description 7
- 238000001757 thermogravimetry curve Methods 0.000 claims description 7
- 239000012456 homogeneous solution Substances 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- 238000010586 diagram Methods 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 238000004804 winding Methods 0.000 claims 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 13
- 238000001556 precipitation Methods 0.000 description 13
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 230000009466 transformation Effects 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000002411 thermogravimetry Methods 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 5
- 238000003109 Karl Fischer titration Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- CTPOHARTNNSRSR-NOQAJONNSA-N 4-[(1r,2r,3as,8bs)-2-hydroxy-1-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2,3,3a,8b-tetrahydro-1h-cyclopenta[b][1]benzofuran-5-yl]butanoic acid Chemical compound O([C@H]1C[C@@H](O)[C@@H]([C@@H]21)/C=C/[C@@H](O)[C@@H](C)CC#CC)C1=C2C=CC=C1CCCC(O)=O CTPOHARTNNSRSR-NOQAJONNSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 3
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- -1 dimethyl acetone Amine Chemical class 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000013557 residual solvent Substances 0.000 description 2
- PAJMKGZZBBTTOY-ZFORQUDYSA-N treprostinil Chemical compound C1=CC=C(OCC(O)=O)C2=C1C[C@@H]1[C@@H](CC[C@@H](O)CCCCC)[C@H](O)C[C@@H]1C2 PAJMKGZZBBTTOY-ZFORQUDYSA-N 0.000 description 2
- JGFBQFKZKSSODQ-UHFFFAOYSA-N Isothiocyanatocyclopropane Chemical compound S=C=NC1CC1 JGFBQFKZKSSODQ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- RDYMFSUJUZBWLH-UHFFFAOYSA-N endosulfan Chemical compound C12COS(=O)OCC2C2(Cl)C(Cl)=C(Cl)C1(Cl)C2(Cl)Cl RDYMFSUJUZBWLH-UHFFFAOYSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229950004586 esuberaprost Drugs 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- KJJSQLNNCPOREA-VIWJKOKZSA-N methyl 4-[(1r,2r,3as,8bs)-2-hydroxy-1-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2,3,3a,8b-tetrahydro-1h-cyclopenta[b][1]benzofuran-5-yl]butanoate Chemical compound COC(=O)CCCC1=CC=CC2=C1O[C@@H]1[C@H]2[C@@H](\C=C\[C@@H](O)[C@@H](C)CC#CC)[C@H](O)C1 KJJSQLNNCPOREA-VIWJKOKZSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 150000003815 prostacyclins Chemical class 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960005032 treprostinil Drugs 0.000 description 1
- 229940014025 tyvaso Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P9/12—Antihypertensives
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16/199,471 US10577341B1 (en) | 2018-11-26 | 2018-11-26 | Beraprost-314d monohydrate crystals and methods for preparation thereof |
| US16/199,471 | 2018-11-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW202021960A TW202021960A (zh) | 2020-06-16 |
| TWI724651B true TWI724651B (zh) | 2021-04-11 |
Family
ID=68655416
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW108143007A TWI724651B (zh) | 2018-11-26 | 2019-11-26 | 貝前列素-314d單水合物晶體及其製備方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US10577341B1 (enExample) |
| EP (1) | EP3656767A1 (enExample) |
| JP (1) | JP6894489B2 (enExample) |
| KR (1) | KR102317032B1 (enExample) |
| CN (1) | CN111217782A (enExample) |
| TW (1) | TWI724651B (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11447440B2 (en) * | 2020-10-29 | 2022-09-20 | Chirogate International Inc. | Treprostinil monohydrate crystals and methods for preparation thereof |
| CN115611838A (zh) * | 2021-07-15 | 2023-01-17 | 四川国为制药有限公司 | 一种前列环素衍生物的晶型 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201808927A (zh) * | 2016-04-05 | 2018-03-16 | 齊諾應醫藥及化學品私人有限公司 | 製備具光學活性之貝前列素（Ｂｅｒａｐｒｏｓｔ）之方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59134787A (ja) * | 1983-01-19 | 1984-08-02 | Toray Ind Inc | ５，６，７−トリノル−４，８−インタ−ｍ−フエニレンＰＧＩ↓２誘導体の製造法 |
| JP4503942B2 (ja) * | 2003-06-11 | 2010-07-14 | 大正製薬株式会社 | 止痒剤 |
| CN105315247B (zh) * | 2011-06-16 | 2019-07-26 | 琅歌生物技术股份有限公司 | 贝前列素的生产方法 |
| WO2014151085A1 (en) * | 2013-03-15 | 2014-09-25 | Gemmus Pharma Inc. | Beraprost isomer as agent for the treatment of viral infection |
| CN103242274B (zh) * | 2013-05-22 | 2014-11-05 | 孙威 | 一种贝前列素钠化合物及其制备方法 |
| KR20170012314A (ko) * | 2014-05-20 | 2017-02-02 | 렁 바이오테크놀로지 인크. | 베라프로스트 및 그의 유도체의 제조 방법 |
| US9765047B2 (en) * | 2015-08-12 | 2017-09-19 | United Therapeutics Corporation | Process for making beraprost |
| KR101777632B1 (ko) * | 2016-04-11 | 2017-09-12 | 연성정밀화학(주) | 베라프로스트 나트륨 결정형 및 이의 제조방법 |
-
2018
- 2018-11-26 US US16/199,471 patent/US10577341B1/en active Active
-
2019
- 2019-11-25 KR KR1020190152168A patent/KR102317032B1/ko active Active
- 2019-11-25 EP EP19211276.1A patent/EP3656767A1/en active Pending
- 2019-11-25 JP JP2019212064A patent/JP6894489B2/ja active Active
- 2019-11-26 CN CN201911176459.6A patent/CN111217782A/zh active Pending
- 2019-11-26 TW TW108143007A patent/TWI724651B/zh active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201808927A (zh) * | 2016-04-05 | 2018-03-16 | 齊諾應醫藥及化學品私人有限公司 | 製備具光學活性之貝前列素（Ｂｅｒａｐｒｏｓｔ）之方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20200063070A (ko) | 2020-06-04 |
| JP6894489B2 (ja) | 2021-06-30 |
| EP3656767A1 (en) | 2020-05-27 |
| KR102317032B1 (ko) | 2021-10-26 |
| JP2020083892A (ja) | 2020-06-04 |
| CN111217782A (zh) | 2020-06-02 |
| US10577341B1 (en) | 2020-03-03 |
| TW202021960A (zh) | 2020-06-16 |
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