CN114341113A - 乙酰化艾曲波帕的新晶型及其制备方法 - Google Patents
乙酰化艾曲波帕的新晶型及其制备方法 Download PDFInfo
- Publication number
- CN114341113A CN114341113A CN202080060760.5A CN202080060760A CN114341113A CN 114341113 A CN114341113 A CN 114341113A CN 202080060760 A CN202080060760 A CN 202080060760A CN 114341113 A CN114341113 A CN 114341113A
- Authority
- CN
- China
- Prior art keywords
- eltrombopag
- acetylated
- crystal form
- degrees
- ray powder
- 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.)
- Pending
Links
- XDXWLKQMMKQXPV-QYQHSDTDSA-N eltrombopag Chemical compound CC1=NN(C=2C=C(C)C(C)=CC=2)C(=O)\C1=N/NC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 XDXWLKQMMKQXPV-QYQHSDTDSA-N 0.000 title claims abstract description 72
- 239000013078 crystal Substances 0.000 title claims abstract description 62
- 229960001069 eltrombopag Drugs 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 25
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 206010043554 thrombocytopenia Diseases 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 8
- 230000005855 radiation Effects 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000012296 anti-solvent Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
- NMJJFJNHVMGPGM-UHFFFAOYSA-N butyl formate Chemical compound CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 claims description 4
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 238000001757 thermogravimetry curve Methods 0.000 claims description 4
- 230000004580 weight loss Effects 0.000 claims description 3
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims description 2
- 238000001228 spectrum Methods 0.000 claims description 2
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- 238000000113 differential scanning calorimetry Methods 0.000 description 10
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- 238000012360 testing method Methods 0.000 description 6
- DJMJHIKGMVJYCW-UHFFFAOYSA-N 2-aminoethanol 3-[3-[[2-(3,4-dimethylphenyl)-5-methyl-3-oxo-1H-pyrazol-4-yl]diazenyl]-2-hydroxyphenyl]benzoic acid Chemical compound CC1=C(C=C(C=C1)N2C(=O)C(=C(N2)C)N=NC3=CC=CC(=C3O)C4=CC(=CC=C4)C(=O)O)C.C(CO)N.C(CO)N DJMJHIKGMVJYCW-UHFFFAOYSA-N 0.000 description 5
- 208000032467 Aplastic anaemia Diseases 0.000 description 5
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- 229910017488 Cu K Inorganic materials 0.000 description 5
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- 102000018358 immunoglobulin Human genes 0.000 description 5
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
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- 210000004369 blood Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
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- 230000009246 food effect Effects 0.000 description 2
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- 230000001506 immunosuppresive effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- FMLGTJWOWQEDOC-UHFFFAOYSA-N 2-aminoethanol 3-[3-[[2-(3,4-dimethylphenyl)-5-methyl-3-oxo-1H-pyrazol-4-yl]diazenyl]-2-hydroxyphenyl]benzoic acid Chemical class CC1=C(C=C(C=C1)N2C(=O)C(=C(N2)C)N=NC3=CC=CC(=C3O)C4=CC(=CC=C4)C(=O)O)C.C(CO)N FMLGTJWOWQEDOC-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 229960001827 eltrombopag olamine Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940126460 thrombopoietin receptor agonist Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D231/08—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms
Abstract
本发明提供了乙酰化艾曲波帕的新晶型及其制备方法，属于药物化学领域。所述晶型具有较好的稳定性有利于储存、转移、生产工艺中操作，其能够在动物体内能良好释放，可以用于制备成制剂。
Description
PCT国内申请，说明书已公开。
Claims (11)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910998901 | 2019-10-21 | ||
| CN2019109989017 | 2019-10-21 | ||
| PCT/CN2020/121711 WO2021078077A1 (zh) | 2019-10-21 | 2020-10-17 | 乙酰化艾曲波帕的新晶型及其制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114341113A true CN114341113A (zh) | 2022-04-12 |
Family
ID=75620393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080060760.5A Pending CN114341113A (zh) | 2019-10-21 | 2020-10-17 | 乙酰化艾曲波帕的新晶型及其制备方法 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN114341113A (zh) |
| WO (1) | WO2021078077A1 (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1444477A (zh) * | 2000-05-25 | 2003-09-24 | 史密丝克莱恩比彻姆公司 | 血小板生成素模拟物 |
| WO2013072921A2 (en) * | 2011-09-13 | 2013-05-23 | Glenmark Generics Limited | Process for preparation of substituted 3'-hydrazino-biphenyl-3-carboxylic acid compounds |
| US20170275255A1 (en) * | 2014-09-05 | 2017-09-28 | Hetero Research Foundation | Crystalline form of eltrombopag free acid |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009249069A1 (en) * | 2008-05-20 | 2009-11-26 | Neurogesx, Inc. | Carbonate prodrugs and methods of using the same |
| CN102448942A (zh) * | 2009-04-01 | 2012-05-09 | 普利瓦赫尔瓦茨卡有限公司 | 艾曲波帕和艾曲波帕盐的多晶型物及其制备方法 |
| US9561285B2 (en) * | 2010-01-22 | 2017-02-07 | Ascendis Pharma As | Carrier-linked carbamate prodrug linkers |
| EP3692021A1 (en) * | 2017-10-06 | 2020-08-12 | Assia Chemical Industries Ltd | Solid state forms of eltrombopag choline |
| CN109096195A (zh) * | 2018-09-27 | 2018-12-28 | 上海雅本化学有限公司 | 一种艾曲波帕的制备方法 |
-
2020
- 2020-10-17 CN CN202080060760.5A patent/CN114341113A/zh active Pending
- 2020-10-17 WO PCT/CN2020/121711 patent/WO2021078077A1/zh active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1444477A (zh) * | 2000-05-25 | 2003-09-24 | 史密丝克莱恩比彻姆公司 | 血小板生成素模拟物 |
| WO2013072921A2 (en) * | 2011-09-13 | 2013-05-23 | Glenmark Generics Limited | Process for preparation of substituted 3'-hydrazino-biphenyl-3-carboxylic acid compounds |
| US20170275255A1 (en) * | 2014-09-05 | 2017-09-28 | Hetero Research Foundation | Crystalline form of eltrombopag free acid |
Non-Patent Citations (1)
| Title |
|---|
| 刘文娟等, 中国医药科技出版社 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021078077A1 (zh) | 2021-04-29 |
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| PB01 | Publication | ||
| PB01 | Publication | ||
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| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 523808 No.1, Gongye North Road, Songshanhu Park, Dongguan City, Guangdong Province Applicant after: Guangdong Dongyangguang Pharmaceutical Co.,Ltd. Address before: 523808 No.1, Gongye North Road, Songshanhu Park, Dongguan City, Guangdong Province Applicant before: SUNSHINE LAKE PHARMA Co.,Ltd. |
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| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20220412 |