CN115093416B - Ttk抑制剂的固体形式 - Google Patents
Ttk抑制剂的固体形式 Download PDFInfo
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- CN115093416B CN115093416B CN202210644487.1A CN202210644487A CN115093416B CN 115093416 B CN115093416 B CN 115093416B CN 202210644487 A CN202210644487 A CN 202210644487A CN 115093416 B CN115093416 B CN 115093416B
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- hydrobromide salt
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Classifications
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B29/00—Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape
- C30B29/54—Organic compounds
- C30B29/58—Macromolecular compounds
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B7/00—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions
- C30B7/02—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions by evaporation of the solvent
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B7/00—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions
- C30B7/14—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions the crystallising materials being formed by chemical reactions in the solution
-
- 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)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Crystallography & Structural Chemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210644487.1A CN115093416B (zh) | 2016-07-18 | 2017-07-13 | Ttk抑制剂的固体形式 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662363424P | 2016-07-18 | 2016-07-18 | |
| US62/363,424 | 2016-07-18 | ||
| CN202210644487.1A CN115093416B (zh) | 2016-07-18 | 2017-07-13 | Ttk抑制剂的固体形式 |
| PCT/CA2017/050848 WO2018014116A1 (en) | 2016-07-18 | 2017-07-13 | Solid forms of ttk inhibitor |
| CN201780043473.1A CN109476667B (zh) | 2016-07-18 | 2017-07-13 | Ttk抑制剂的固体形式 |
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| CN201780043473.1A Division CN109476667B (zh) | 2016-07-18 | 2017-07-13 | Ttk抑制剂的固体形式 |
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| CN115093416A CN115093416A (zh) | 2022-09-23 |
| CN115093416B true CN115093416B (zh) | 2024-04-12 |
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|---|---|---|---|---|
| AU2017299850B2 (en) | 2016-07-18 | 2021-05-27 | University Health Network | Solid forms of TTK inhibitor |
| KR20240175121A (ko) | 2023-06-12 | 2024-12-19 | 한국재료연구원 | 희토류 산화물을 이용한 입계확산물질의 제조방법 및 이를 이용한 R-Fe-B계 영구자석의 제조방법 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103415518A (zh) * | 2010-12-17 | 2013-11-27 | 拜耳知识产权有限责任公司 | 在过度增殖性病症的治疗中用作mps-1和tkk抑制剂的咪唑并吡嗪 |
| WO2014075168A1 (en) * | 2012-11-16 | 2014-05-22 | University Health Network | Pyrazolopyrimidine compounds |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2438092C (en) | 2001-02-21 | 2011-08-09 | Chiron Corporation | Ttk in diagnosis and as a therapeutic target in cancer |
| ATE482213T1 (de) * | 2004-11-04 | 2010-10-15 | Vertex Pharma | Als inhibitoren von proteinkinasen geeignete pyrazoloä1,5-aüpyrimidine |
| TW201107329A (en) * | 2009-07-30 | 2011-03-01 | Oncotherapy Science Inc | Fused imidazole derivative having ttk inhibitory action |
| TWI541243B (zh) * | 2010-09-10 | 2016-07-11 | 拜耳知識產權公司 | 經取代咪唑并嗒 |
| JP6095857B2 (ja) * | 2013-11-15 | 2017-03-15 | ユニバーシティ・ヘルス・ネットワーク | ピラゾロピリミジン化合物 |
| AU2017299850B2 (en) | 2016-07-18 | 2021-05-27 | University Health Network | Solid forms of TTK inhibitor |
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- 2017-07-13 DK DK17830139.6T patent/DK3484888T3/da active
- 2017-07-18 TW TW106123975A patent/TWI745400B/zh active
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103415518A (zh) * | 2010-12-17 | 2013-11-27 | 拜耳知识产权有限责任公司 | 在过度增殖性病症的治疗中用作mps-1和tkk抑制剂的咪唑并吡嗪 |
| WO2014075168A1 (en) * | 2012-11-16 | 2014-05-22 | University Health Network | Pyrazolopyrimidine compounds |
| WO2015070349A1 (en) * | 2012-11-16 | 2015-05-21 | University Health Network | Pyrazolopyrimidine compounds |
Non-Patent Citations (3)
| Title |
|---|
| "抗肿瘤药LS-177的药物动力学研究";张健 等;《中国药剂学杂志》;第13卷(第5期);第173-180页 * |
| Yong Liu，et al.."Discovery of Pyrazolo[1,5‑a]pyrimidine TTK Inhibitors: CFI-402257 is a Potent, Selective, Bioavailable Anticancer Agent".《ACS Med. Chem. Lett.》.2016,第7卷第671-675页. * |
| 倪春燕 等."吡唑并[1,5-a]嘧啶类c-Met 激酶抑制剂的合成及生物活性研究".《有机化学》.2012,第32卷第2294-2299页. * |
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