CN118388495A - 作为HER2抑制剂的[1,3]二嗪基[5,4-d]嘧啶 - Google Patents
作为HER2抑制剂的[1,3]二嗪基[5,4-d]嘧啶 Download PDFInfo
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- CN118388495A CN118388495A CN202410508211.XA CN202410508211A CN118388495A CN 118388495 A CN118388495 A CN 118388495A CN 202410508211 A CN202410508211 A CN 202410508211A CN 118388495 A CN118388495 A CN 118388495A
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| TW202510886A (zh) | 2023-05-31 | 2025-03-16 | 德商百靈佳殷格翰國際股份有限公司 | 作為用於預測癌症治療反應性之生物標記之存活素 |
| CN116903615A (zh) * | 2023-06-21 | 2023-10-20 | 江苏丽源医药有限公司 | 一种妥卡替尼及其中间体的制备方法 |
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| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| WO2025051693A1 (en) * | 2023-09-06 | 2025-03-13 | Boehringer Ingelheim International Gmbh | Cancer treatment with a her2 inhibitor and a cyp3a and/or p-gp modulator |
| TW202530228A (zh) | 2023-10-12 | 2025-08-01 | 美商銳新醫藥公司 | Ｒａｓ抑制劑 |
| WO2025132522A1 (en) | 2023-12-20 | 2025-06-26 | Boehringer Ingelheim International Gmbh | Anti-cancer combination therapy |
| WO2025132549A1 (en) | 2023-12-20 | 2025-06-26 | Boehringer Ingelheim International Gmbh | Cancer combination therapy using zongertinib and a kras g12c inhibitor |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025210042A1 (en) * | 2024-04-03 | 2025-10-09 | Boehringer Ingelheim International Gmbh | Combination of zongertinib with a sos1 inhibitor for use in the treatment of cancer |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025255438A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| US20250376476A1 (en) | 2024-06-11 | 2025-12-11 | Boehringer Ingelheim International Gmbh | Crystalline forms of a HER2 tyrosine kinase inhibitor |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
| DE19608588A1 (de) | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido [5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| CN1602195A (zh) | 2001-12-12 | 2005-03-30 | 辉瑞产品公司 | 用于治疗异常细胞生长的喹唑啉衍生物 |
| WO2005044302A1 (en) | 2003-11-06 | 2005-05-19 | Pfizer Products Inc. | Selective erbb2 inhibitor/anti-erbb antibody combinations in the treatment of cancer |
| DK1971601T3 (da) | 2005-11-15 | 2010-02-08 | Array Biopharma Inc | N4-phenyl-quinazolin-4-aminderivater og beslægtede forbindelser som ERBB Type 1-receptortyrosinkinase-inhibitorer til behandling af hyperproliferative sygdomme |
| WO2007059217A2 (en) * | 2005-11-16 | 2007-05-24 | Lonnie Lehrer | Automobile propulsion system |
| US20170166598A1 (en) | 2014-05-13 | 2017-06-15 | Ariad Pharmaceuticals, Inc. | Heteroaryl compounds for kinase inhibition |
| BR112016029662B1 (pt) | 2014-06-19 | 2023-10-24 | Takeda Pharmaceutical Company Limited | COMPOSTO DE FÓRMULA Bf OU UMA FORMA FARMACEUTICAMENTE ACEITÁVEL DO MESMO, COMPOSIÇÃO FARMACÊUTICA COMPREENDENDO O MESMO E SEU USO |
| WO2016183278A1 (en) | 2015-05-13 | 2016-11-17 | Ariad Pharmaceuticals, Inc. | Heteroaryl compounds for kinase inhibition |
| CN111032655B (zh) | 2017-08-31 | 2022-09-02 | 达纳-法伯癌症研究所股份有限公司 | Egfr和/或her2抑制剂和使用方法 |
| JP7333313B2 (ja) | 2017-09-01 | 2023-08-24 | シャンハイ ファーマシューティカルズ ホールディング カンパニー，リミティド | 窒素含有複素環化合物、製造方法、中間体、組成物および使用 |
| JP7626774B2 (ja) | 2020-02-03 | 2025-02-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ＨＥＲ２阻害薬としての［１，３］ジアジノ［５，４－ｄ］ピリミジン |
| EP4100409B1 (en) | 2020-02-03 | 2024-08-28 | Boehringer Ingelheim International GmbH | [1,3]diazino[5,4-d]pyrimidines as her2 inhibitors |
| US11608343B2 (en) | 2020-04-24 | 2023-03-21 | Boehringer Ingelheim International Gmbh | Substituted pyrimido[5,4-d]pyrimidines as HER2 inhibitors |
| WO2021231400A1 (en) * | 2020-05-12 | 2021-11-18 | Accutar Biotechnology, Inc. | Bis-aryl ethers containing n-acyl azetidine as egfr/her2 inhibitors |
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