CN109548403A - Galunisertib的晶型及其制备方法和用途 - Google Patents
Galunisertib的晶型及其制备方法和用途 Download PDFInfo
- Publication number
- CN109548403A CN109548403A CN201780028843.4A CN201780028843A CN109548403A CN 109548403 A CN109548403 A CN 109548403A CN 201780028843 A CN201780028843 A CN 201780028843A CN 109548403 A CN109548403 A CN 109548403A
- Authority
- CN
- China
- Prior art keywords
- crystal form
- present
- crystal
- galunisertib
- moist
- 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
- 239000013078 crystal Substances 0.000 title claims abstract description 130
- IVRXNBXKWIJUQB-UHFFFAOYSA-N LY-2157299 Chemical compound CC1=CC=CC(C=2C(=C3CCCN3N=2)C=2C3=CC(=CC=C3N=CC=2)C(N)=O)=N1 IVRXNBXKWIJUQB-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 229950000456 galunisertib Drugs 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 32
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000011287 therapeutic dose Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 14
- 229940079593 drug Drugs 0.000 abstract description 12
- 238000005457 optimization Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 14
- 238000000034 method Methods 0.000 description 12
- 238000009826 distribution Methods 0.000 description 10
- 239000002245 particle Substances 0.000 description 9
- 238000002411 thermogravimetry Methods 0.000 description 9
- 238000000227 grinding Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 229910016860 FaSSIF Inorganic materials 0.000 description 5
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
- 230000004584 weight gain Effects 0.000 description 5
- 235000019786 weight gain Nutrition 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 229910005429 FeSSIF Inorganic materials 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910001868 water Inorganic materials 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000000113 differential scanning calorimetry Methods 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- CNPVJWYWYZMPDS-UHFFFAOYSA-N 2-methyldecane Chemical group CCCCCCCCC(C)C CNPVJWYWYZMPDS-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 229910017488 Cu K Inorganic materials 0.000 description 1
- 229910017541 Cu-K Inorganic materials 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 238000001237 Raman spectrum Methods 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Galunisertib的晶型A及其制备方法和用途，该晶型具有良好的稳定性和溶解性、较低的引湿性等有利性能，对未来该药物的优化和开发具有重要价值。
Description
PCT国内申请，说明书已公开。
Claims (6)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610533326 | 2016-07-07 | ||
| PCT/CN2017/092233 WO2018006870A1 (zh) | 2016-07-07 | 2017-07-21 | Galunisertib的晶型及其制备方法和用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109548403A true CN109548403A (zh) | 2019-03-29 |
Family
ID=60912012
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780028843.4A Pending CN109548403A (zh) | 2016-07-07 | 2017-07-21 | Galunisertib的晶型及其制备方法和用途 |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US10604528B2 (zh) |
| CN (1) | CN109548403A (zh) |
| WO (1) | WO2018006870A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN120037236A (zh) * | 2023-11-24 | 2025-05-27 | 浙江同源康医药股份有限公司 | 晶体、药物组合物及其制备方法和应用 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018165979A1 (zh) | 2017-03-17 | 2018-09-20 | 杭州领业医药科技有限公司 | 2-(6-甲基-吡啶-2-基)-3-基-[6-酰胺基-喹啉-4-基]-5,6-二氢-4H-吡咯并[1,2-b]吡唑的晶型及其制备方法和药物组合物 |
| WO2019042383A1 (zh) * | 2017-08-31 | 2019-03-07 | 苏州科睿思制药有限公司 | Galunisertib的晶型及其制备方法和用途 |
| WO2019137027A1 (zh) * | 2018-01-12 | 2019-07-18 | 苏州科睿思制药有限公司 | Galunisertib的晶型及其制备方法和用途 |
| PT118716A (pt) * | 2023-06-12 | 2024-12-12 | Saude Viavel Sa | Galunisertib para uso no tratamento da alopecia androgénica |
| EP4525869A1 (en) * | 2022-06-17 | 2025-03-26 | Saúde Viável, S.A. | Galunisertib for use in the treatment of androgenic alopecia |
| GB202309553D0 (en) * | 2023-06-24 | 2023-08-09 | Ucl Business Ltd | Compostions and uses thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1714090A (zh) * | 2002-11-22 | 2005-12-28 | 伊莱利利公司 | 喹啉基－吡咯并吡唑化合物 |
| CN110582497A (zh) * | 2017-03-17 | 2019-12-17 | 杭州领业医药科技有限公司 | 2-(6-甲基-吡啶-2-基)-3-基-[6-酰胺基-喹啉-4-基]-5,6-二氢-4H-吡咯并[1,2-b]吡唑的晶型及其制备方法和药物组合物 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6627646B2 (en) * | 2001-07-17 | 2003-09-30 | Sepracor Inc. | Norastemizole polymorphs |
| SI1910370T1 (sl) | 2005-07-22 | 2015-06-30 | Eli Lilly And Company | Piridin kinolin substituirani pirolo(1,2-b)pirazol monohidrat kot tgf-beta inhibitor |
-
2017
- 2017-07-21 US US16/315,242 patent/US10604528B2/en not_active Expired - Fee Related
- 2017-07-21 CN CN201780028843.4A patent/CN109548403A/zh active Pending
- 2017-07-21 WO PCT/CN2017/092233 patent/WO2018006870A1/zh not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1714090A (zh) * | 2002-11-22 | 2005-12-28 | 伊莱利利公司 | 喹啉基－吡咯并吡唑化合物 |
| CN110582497A (zh) * | 2017-03-17 | 2019-12-17 | 杭州领业医药科技有限公司 | 2-(6-甲基-吡啶-2-基)-3-基-[6-酰胺基-喹啉-4-基]-5,6-二氢-4H-吡咯并[1,2-b]吡唑的晶型及其制备方法和药物组合物 |
Non-Patent Citations (1)
| Title |
|---|
| JEFFRY K. NIEMEIER ET AL.: "Application of Kinetic Modeling and Competitive Solvent Hydrolysis in the Development of a Highly Selective Hydrolysis of a Nitrile to an Amide", 《ORG. PROCESS RES. DEV.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN120037236A (zh) * | 2023-11-24 | 2025-05-27 | 浙江同源康医药股份有限公司 | 晶体、药物组合物及其制备方法和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2018006870A1 (zh) | 2018-01-11 |
| US10604528B2 (en) | 2020-03-31 |
| US20190241572A1 (en) | 2019-08-08 |
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| WD01 | Invention patent application deemed withdrawn after publication |
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