JP7390313B2 - Ａｘｌ／ｍｅｒ ｒｔｋおよびｃｓｆ１ｒの阻害剤としてのキノリン誘導体 - Google Patents
Ａｘｌ／ｍｅｒ ｒｔｋおよびｃｓｆ１ｒの阻害剤としてのキノリン誘導体 Download PDFInfo
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| US201862677902P | 2018-05-30 | 2018-05-30 | |
| US62/677,902 | 2018-05-30 | ||
| PCT/EP2019/064214 WO2019229251A1 (en) | 2018-05-30 | 2019-05-31 | Quinoline derivatives as inhibitors of axl/mer rtk and csf1r |
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| JP2021525270A JP2021525270A (ja) | 2021-09-24 |
| JP2021525270A5 JP2021525270A5 (enExample) | 2021-12-09 |
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| JP2023174642A Withdrawn JP2023168629A (ja) | 2018-05-30 | 2023-10-06 | Ａｘｌ／ｍｅｒ ｒｔｋおよびｃｓｆ１ｒの阻害剤としてのキノリン誘導体 |
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| GB201905721D0 (en) | 2019-04-24 | 2019-06-05 | Univ Dundee | Compounds |
| IL315474A (en) * | 2022-03-30 | 2024-11-01 | Qurient Co Ltd | New forms of n-(5-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-2-yl)-1-propyl-4-(2,2,2-trifluoroethoxy)-1h-pyrazole-3 -carboxamide hydrochloride |
| CN117637185B (zh) * | 2024-01-25 | 2024-04-23 | 首都医科大学宣武医院 | 一种基于影像的颅咽管瘤治疗辅助决策方法、系统及设备 |
| CN118593494B (zh) * | 2024-08-08 | 2024-11-01 | 四川大学华西医院 | Nampt抑制剂在制备预防和/或治疗色素沉着绒毛结节性滑膜炎的药物中的用途 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997017329A1 (en) | 1995-11-07 | 1997-05-15 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of growth factor receptor originating in platelet and pharmaceutical compositions containing the same |
| WO2011045084A1 (en) | 2009-10-16 | 2011-04-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Quinolinyloxyphenylsulfonamides |
| JP2013536813A (ja) | 2010-08-28 | 2013-09-26 | リード ディスカバリー センター ゲーエムベーハー | Ａｘｌ阻害剤としての薬学的に活性な化合物 |
| JP2014506925A (ja) | 2011-02-28 | 2014-03-20 | カリトル サイエンシズ， エルエルシー | 置換型キノリン化合物及び使用方法 |
| WO2016104617A1 (ja) | 2014-12-25 | 2016-06-30 | 小野薬品工業株式会社 | キノリン誘導体 |
| JP2018511624A (ja) | 2015-04-14 | 2018-04-26 | キュリエント カンパニー， リミテッド | Ｔａｍ ｒｔｋインヒビターとしてのキノリン誘導体 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019231942A1 (en) | 2018-06-01 | 2019-12-05 | Rigel Pharmaceuticals, Inc. | Quinoline derivatives useful as tyrosine kinase inhibitors |
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- 2019-05-31 JP JP2020565928A patent/JP7390313B2/ja active Active
- 2019-05-31 BR BR112020021370-5A patent/BR112020021370A2/pt unknown
- 2019-05-31 WO PCT/EP2019/064214 patent/WO2019229251A1/en not_active Ceased
- 2019-05-31 CN CN201980036560.3A patent/CN112313216B/zh active Active
- 2019-05-31 MX MX2020011636A patent/MX2020011636A/es unknown
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- 2019-05-31 EP EP19728645.3A patent/EP3774776A1/en active Pending
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2020
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2023
- 2023-10-06 JP JP2023174642A patent/JP2023168629A/ja not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997017329A1 (en) | 1995-11-07 | 1997-05-15 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of growth factor receptor originating in platelet and pharmaceutical compositions containing the same |
| WO2011045084A1 (en) | 2009-10-16 | 2011-04-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Quinolinyloxyphenylsulfonamides |
| JP2013536813A (ja) | 2010-08-28 | 2013-09-26 | リード ディスカバリー センター ゲーエムベーハー | Ａｘｌ阻害剤としての薬学的に活性な化合物 |
| JP2014506925A (ja) | 2011-02-28 | 2014-03-20 | カリトル サイエンシズ， エルエルシー | 置換型キノリン化合物及び使用方法 |
| WO2016104617A1 (ja) | 2014-12-25 | 2016-06-30 | 小野薬品工業株式会社 | キノリン誘導体 |
| JP2018511624A (ja) | 2015-04-14 | 2018-04-26 | キュリエント カンパニー， リミテッド | Ｔａｍ ｒｔｋインヒビターとしてのキノリン誘導体 |
Non-Patent Citations (2)
| Title |
|---|
| Journal of Medicinal Chemistry，2015年11月10日，Vol.59(8)，p.3593-3608 |
| RN:2028271-26-1，DATABASE REGISTRY [Online], Retrieved from STN，2016年11月09日 |
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| PH12020551806A1 (en) | 2021-05-17 |
| US20210163448A1 (en) | 2021-06-03 |
| JP2023168629A (ja) | 2023-11-24 |
| CN112313216A (zh) | 2021-02-02 |
| US12162858B2 (en) | 2024-12-10 |
| KR20210020882A (ko) | 2021-02-24 |
| IL278960B2 (en) | 2024-08-01 |
| IL278960A (en) | 2021-01-31 |
| SG11202009971QA (en) | 2020-11-27 |
| AU2019276359B2 (en) | 2024-10-03 |
| BR112020021370A2 (pt) | 2021-01-19 |
| CN112313216B (zh) | 2025-03-14 |
| AU2019276359A1 (en) | 2020-10-29 |
| NZ768747A (en) | 2025-06-27 |
| MX2020011636A (es) | 2020-12-07 |
| IL278960B1 (en) | 2024-04-01 |
| JP2021525270A (ja) | 2021-09-24 |
| CA3097694A1 (en) | 2019-12-05 |
| WO2019229251A1 (en) | 2019-12-05 |
| EP3774776A1 (en) | 2021-02-17 |
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