JP7358466B2 - Ｌｓｄ１阻害剤の塩及びその結晶型 - Google Patents
Ｌｓｄ１阻害剤の塩及びその結晶型 Download PDFInfo
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- JP7358466B2 JP7358466B2 JP2021525358A JP2021525358A JP7358466B2 JP 7358466 B2 JP7358466 B2 JP 7358466B2 JP 2021525358 A JP2021525358 A JP 2021525358A JP 2021525358 A JP2021525358 A JP 2021525358A JP 7358466 B2 JP7358466 B2 JP 7358466B2
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Images
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- 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
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| WO2021228146A1 (zh) * | 2020-05-12 | 2021-11-18 | 石药集团中奇制药技术（石家庄）有限公司 | 一种lsd1抑制剂的用途 |
| US20250073232A1 (en) | 2021-04-08 | 2025-03-06 | Oryzon Genomics, S.A. | Combinations of lsd1 inhibitors for treating myeloid cancers |
| EP4522136A1 (en) | 2022-05-09 | 2025-03-19 | Oryzon Genomics, S.A. | Methods of treating malignant peripheral nerve sheath tumor (mpnst) using lsd1 inhibitors |
| US20250295660A1 (en) | 2022-05-09 | 2025-09-25 | Oryzon Genomics, S.A. | Methods of treating nf1-mutant tumors using lsd1 inhibitors |
| CN120529900A (zh) | 2022-11-24 | 2025-08-22 | 奥莱松基因组股份有限公司 | 用于治疗癌症的LSD1抑制剂和Menin抑制剂的组合 |
| CN116069221A (zh) * | 2022-12-27 | 2023-05-05 | 北京字跳网络技术有限公司 | 媒体内容的展示方法、装置、电子设备和存储介质 |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| AU2024360465A1 (en) | 2023-10-12 | 2026-04-09 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| TW202547461A (zh) | 2024-05-17 | 2025-12-16 | 美商銳新醫藥公司 | Ｒａｓ抑制劑 |
| WO2025255438A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026015801A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026050446A1 (en) | 2024-08-29 | 2026-03-05 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026072904A2 (en) | 2024-09-26 | 2026-04-02 | Revolution Medicines, Inc. | Compositions and methods for treating lung cancer |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010084160A1 (en) | 2009-01-21 | 2010-07-29 | Oryzon Genomics S.A. | Phenylcyclopropylamine derivatives and their medical use |
| JP2013525331A (ja) | 2010-04-19 | 2013-06-20 | オリゾン・ジェノミックス・ソシエダッド・アノニマ | リジン特異的脱メチル化酵素１阻害薬およびその使用 |
| JP2013535460A (ja) | 2010-07-29 | 2013-09-12 | オリゾン・ジェノミックス・ソシエダッド・アノニマ | Ｌｓｄ１のアリールシクロプロピルアミンをベースとしたデメチラーゼ阻害剤およびそれらの医学的使用 |
| JP2014515013A (ja) | 2011-03-25 | 2014-06-26 | グラクソスミスクライン、インテレクチュアル、プロパティー、ナンバー２、リミテッド | Ｌｓｄ１阻害剤としてのシクロプロピルアミン |
| WO2017184934A1 (en) | 2016-04-22 | 2017-10-26 | Incyte Corporation | Formulations of an lsd1 inhibitor |
| WO2017195216A1 (en) | 2016-05-09 | 2017-11-16 | Jubilant Biosys Limited | Cyclopropyl-amide compounds as dual lsd1/hdac inhibitors |
| JP7217712B2 (ja) | 2017-01-24 | 2023-02-03 | シーエスピーシー ジョォンチィ ファーマシューティカル テクノロジー （シージアジョァン）カンパニー，リミテッド | Ｌｓｄ１阻害剤、その製造方法及び応用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2705675B1 (fr) * | 1993-05-27 | 1996-05-03 | Smithkline Beecham Labo Pharma | Nouveaux composés, leur procédé de préparation et leur utilisation en tant que médicaments. |
| MY189367A (en) * | 2015-08-12 | 2022-02-08 | Incyte Corp | Salts of an lsd1 inhibitor |
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Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010084160A1 (en) | 2009-01-21 | 2010-07-29 | Oryzon Genomics S.A. | Phenylcyclopropylamine derivatives and their medical use |
| JP2013525331A (ja) | 2010-04-19 | 2013-06-20 | オリゾン・ジェノミックス・ソシエダッド・アノニマ | リジン特異的脱メチル化酵素１阻害薬およびその使用 |
| JP2013535460A (ja) | 2010-07-29 | 2013-09-12 | オリゾン・ジェノミックス・ソシエダッド・アノニマ | Ｌｓｄ１のアリールシクロプロピルアミンをベースとしたデメチラーゼ阻害剤およびそれらの医学的使用 |
| JP2014515013A (ja) | 2011-03-25 | 2014-06-26 | グラクソスミスクライン、インテレクチュアル、プロパティー、ナンバー２、リミテッド | Ｌｓｄ１阻害剤としてのシクロプロピルアミン |
| WO2017184934A1 (en) | 2016-04-22 | 2017-10-26 | Incyte Corporation | Formulations of an lsd1 inhibitor |
| WO2017195216A1 (en) | 2016-05-09 | 2017-11-16 | Jubilant Biosys Limited | Cyclopropyl-amide compounds as dual lsd1/hdac inhibitors |
| JP7217712B2 (ja) | 2017-01-24 | 2023-02-03 | シーエスピーシー ジョォンチィ ファーマシューティカル テクノロジー （シージアジョァン）カンパニー，リミテッド | Ｌｓｄ１阻害剤、その製造方法及び応用 |
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| EP3825309A1 (en) | 2021-05-26 |
| JP2021530565A (ja) | 2021-11-11 |
| AU2019303777A1 (en) | 2021-02-11 |
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| CA3106484C (en) | 2024-06-25 |
| WO2020015745A1 (zh) | 2020-01-23 |
| EP3825309B1 (en) | 2023-09-06 |
| CA3106484A1 (en) | 2020-01-23 |
| KR102778948B1 (ko) | 2025-03-07 |
| CN112424175B (zh) | 2022-10-28 |
| KR20210034058A (ko) | 2021-03-29 |
| AU2019303777B2 (en) | 2023-01-19 |
| US12024494B2 (en) | 2024-07-02 |
| US20210317096A1 (en) | 2021-10-14 |
| CN112424175A (zh) | 2021-02-26 |
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