CN106687457B - 用于激酶抑制的杂芳基化合物 - Google Patents
用于激酶抑制的杂芳基化合物 Download PDFInfo
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- CN106687457B CN106687457B CN201580037958.0A CN201580037958A CN106687457B CN 106687457 B CN106687457 B CN 106687457B CN 201580037958 A CN201580037958 A CN 201580037958A CN 106687457 B CN106687457 B CN 106687457B
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- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
-
- 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
- C07D487/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| US201461992742P | 2014-05-13 | 2014-05-13 | |
| US61/992,742 | 2014-05-13 | ||
| PCT/US2015/030522 WO2015175632A1 (en) | 2014-05-13 | 2015-05-13 | Heteroaryl compounds for kinase inhibition |
Publications (2)
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| CN106687457A CN106687457A (zh) | 2017-05-17 |
| CN106687457B true CN106687457B (zh) | 2020-01-10 |
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| CN201580037958.0A Expired - Fee Related CN106687457B (zh) | 2014-05-13 | 2015-05-13 | 用于激酶抑制的杂芳基化合物 |
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| US (1) | US20170166598A1 (enExample) |
| EP (1) | EP3143015B1 (enExample) |
| JP (1) | JP6468611B2 (enExample) |
| CN (1) | CN106687457B (enExample) |
| WO (1) | WO2015175632A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12466825B2 (en) | 2019-11-14 | 2025-11-11 | Amgen Inc. | Synthesis of KRAS G12C inhibitor compound |
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| EP2704572B1 (en) | 2011-05-04 | 2015-12-30 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| EP3157916B1 (en) * | 2014-06-19 | 2018-12-12 | ARIAD Pharmaceuticals, Inc. | Heteroaryl compounds for kinase inhibition |
| US10259820B2 (en) * | 2014-10-11 | 2019-04-16 | Shanghai Hansoh Biomedical Co., Ltd. | EGFR inhibitor, preparation method and use thereof |
| CN105085489B (zh) | 2014-11-05 | 2019-03-01 | 益方生物科技（上海）有限公司 | 嘧啶或吡啶类化合物、其制备方法和医药用途 |
| WO2016173438A1 (zh) * | 2015-04-29 | 2016-11-03 | 南京明德新药研发股份有限公司 | 稠环或三环芳基嘧啶化合物用作激酶抑制剂 |
| US20210323976A1 (en) * | 2015-05-13 | 2021-10-21 | Ariad Pharmaceuticals, Inc. | Heteroaryl compounds for kinase inhibition |
| CN106810553B (zh) * | 2015-11-30 | 2020-03-17 | 江苏正大丰海制药有限公司 | 3-(4,5-取代氨基嘧啶)苯基衍生物及其应用 |
| KR20180105161A (ko) | 2016-01-07 | 2018-09-27 | 씨에스 파마테크 리미티드 | Egfr 티로신 키나제의 임상적으로 중요한 돌연변이체의 선택적 억제제 |
| CN107344934B (zh) * | 2016-05-04 | 2019-08-23 | 江苏正大丰海制药有限公司 | 药物活性物质的固体形式 |
| ES2863925T3 (es) * | 2016-09-19 | 2021-10-13 | Nanjing Chuangte Pharmaceutical Tech Co Ltd | Derivados de 3-(pirimidinamina 4,5-sustituida)fenilo deuterados y aplicaciones de los mismos |
| JOP20190073A1 (ar) | 2016-10-31 | 2019-04-07 | Taiho Pharmaceutical Co Ltd | مثبط انتقائي لمستقبل عامل نمو بشروي (egfr) لطافر إدخال exon 20 |
| WO2018119441A1 (en) | 2016-12-23 | 2018-06-28 | Arvinas, Inc. | Egfr proteolysis targeting chimeric molecules and associated methods of use |
| AR111469A1 (es) | 2017-04-21 | 2019-07-17 | Yuhan Corp | Sal de un compuesto del derivado de aminopiridina, una forma cristalina de la misma, y un proceso para preparar la misma |
| MY198379A (en) | 2017-07-28 | 2023-08-28 | Yuhan Corp | Improved Process for Preparing Aminopyrimidine Derivatives |
| US11701359B2 (en) | 2017-09-01 | 2023-07-18 | Taiho Pharmaceutical Co., Ltd. | Exon 18 and/or exon 21 mutant EGFR selective inhibitor |
| EP3613738A1 (en) * | 2018-08-23 | 2020-02-26 | Lead Discovery Center GmbH | 4-substituted pyrrolo[2,3-b]pyridine as erbb modulators useful for treating cancer |
| BR112021012687A2 (pt) | 2018-12-28 | 2021-09-28 | Taiho Pharmaceutical Co., Ltd. | Inibidor de egfr resistente a tratamento de mutante l718 e/ou l792 |
| US12157730B2 (en) | 2019-03-19 | 2024-12-03 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| CA3134261A1 (en) | 2019-03-19 | 2020-09-24 | Voronoi Inc. | 6-(isooxazolidin-2-yl)-n-phenylpyrimidin-4-amine derivatives as inhibitors of epidermal growth factor receptors |
| BR112021019998B1 (pt) * | 2019-04-24 | 2024-01-16 | The Broad Institute, Inc. | 4h-pirrolo[3,2-c]piridin-4-ona, seus usos, composição farmacêutica, e kit de partes |
| US12433597B2 (en) * | 2019-06-04 | 2025-10-07 | Trisalus Life Sciences, Inc. | Atraumatic occlusive system with compartment for measurement of vascular pressure change |
| CA3150927A1 (en) | 2019-09-13 | 2021-03-18 | Holistick Medical | Medical implant, delivery device, method of producing a medical implant, and method of delivering a medical implant |
| CN110746307B (zh) * | 2019-11-01 | 2021-07-06 | 韶远科技（上海)有限公司 | 一种1-硝基-2-乙基-4-氟苯的制备方法 |
| US20210161897A1 (en) | 2019-11-12 | 2021-06-03 | Astrazeneca Ab | Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of cancer |
| AU2021211871A1 (en) | 2020-01-20 | 2022-09-08 | Astrazeneca Ab | Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of cancer |
| US20230126204A1 (en) | 2020-02-03 | 2023-04-27 | Boehringer Ingelheim International Gmbh | [1,3]DIAZINO[5,4-d]PYRIMIDINES AS HER2 INHIBITORS |
| CN115052881B (zh) * | 2020-02-03 | 2024-07-09 | 勃林格殷格翰国际有限公司 | 作为HER2抑制剂的[1,3]二嗪并[5,4-d]嘧啶 |
| US11608343B2 (en) | 2020-04-24 | 2023-03-21 | Boehringer Ingelheim International Gmbh | Substituted pyrimido[5,4-d]pyrimidines as HER2 inhibitors |
| US20210369709A1 (en) | 2020-05-27 | 2021-12-02 | Astrazeneca Ab | EGFR TKIs FOR USE IN THE TREATMENT OF NON-SMALL CELL LUNG CANCER |
| EP4217070A1 (en) | 2020-09-23 | 2023-08-02 | Scorpion Therapeutics, Inc. | Pyrrolo[3,2-c]pyridin-4-one derivatives useful in the treatment of cancer |
| WO2022072645A2 (en) | 2020-09-30 | 2022-04-07 | Scorpion Therapeutics, Inc. | Methods for treating cancer |
| WO2022072632A1 (en) | 2020-09-30 | 2022-04-07 | Scorpion Therapeutics, Inc. | Bicyclic compounds for use in the treatment cancer |
| TW202229282A (zh) | 2020-09-30 | 2022-08-01 | 美商史考皮恩治療有限公司 | 治療癌症之方法 |
| JP2023548657A (ja) | 2020-10-09 | 2023-11-20 | スコーピオン セラピューティクス インコーポレイテッド | がんの処置に使用するための、ｅｇｆｒおよび／またはｈｅｒ２のヘテロ環阻害剤 |
| WO2022094271A1 (en) | 2020-10-30 | 2022-05-05 | Scorpion Therapeutics, Inc. | Methods for treating cancer |
| WO2022098992A1 (en) | 2020-11-05 | 2022-05-12 | Scorpion Therapeutics, Inc. | Use of macrocyclic compounds in methods of treating cancer |
| WO2022197913A1 (en) | 2021-03-18 | 2022-09-22 | Scorpion Therapeutics, Inc. | Bicyclic derivatives which can be used to treat cancer |
| EP4323356A1 (en) | 2021-04-13 | 2024-02-21 | Nuvalent, Inc. | Amino-substituted heterocycles for treating cancers with egfr mutations |
| WO2023173083A1 (en) | 2022-03-11 | 2023-09-14 | Scorpion Therapeutics, Inc. | Tetrahydroindole derivatives as egfr and/or her2 inhibtors useful for the treatment of cancer |
| IL315848A (en) | 2022-03-31 | 2024-11-01 | Astrazeneca Ab | Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in combination with an AKT inhibitor for cancer treatment |
| CN114957224B (zh) * | 2022-05-17 | 2024-03-19 | 浙大城市学院 | 一种肿瘤低氧靶向的egfr抑制剂及其应用 |
| KR20250029133A (ko) | 2022-06-27 | 2025-03-04 | 아스트라제네카 아베 | 암 치료를 위한 표피성장인자 수용체 티로신 키나제 억제제를 포함하는 조합물 |
| CN119654152A (zh) | 2022-07-08 | 2025-03-18 | 阿斯利康(瑞典)有限公司 | 与hgf-受体抑制剂组合用于治疗癌症的表皮生长因子受体酪氨酸激酶抑制剂 |
| CN120359211A (zh) * | 2022-12-08 | 2025-07-22 | 盐野义制药株式会社 | 具有血清素受体结合活性的含氮杂环和碳环衍生物 |
| WO2024254298A1 (en) | 2023-06-08 | 2024-12-12 | Scorpion Therapeutics, Inc. | A 1,5-dihydro-4h-pyrrolo[3,2-c] pyridin-4-one for use in the treatment of cancer |
| WO2024254266A1 (en) | 2023-06-08 | 2024-12-12 | Scorpion Therapeutics, Inc. | A 1,5-dihydro-4h-pyrrolo[3,2-c] pyridin-4-one for use in the treatment of cancer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009158571A1 (en) * | 2008-06-27 | 2009-12-30 | Avila Therapeutics And Uses Thereof | Heteroaryl compounds and uses thereof |
| WO2013014448A1 (en) * | 2011-07-27 | 2013-01-31 | Astrazeneca Ab | 2 - (2, 4, 5 - substituted -anilino) pyrimidine derivatives as egfr modulators useful for treating cancer |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0311274D0 (en) * | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
| SI1948180T1 (sl) * | 2005-11-11 | 2013-06-28 | Boehringer Ingelheim International Gmbh | Kombinacijsko zdravljenje raka, ki obsega EGFR/HER2 inhibitorje |
| ES2417148T3 (es) * | 2007-06-08 | 2013-08-06 | Genentech, Inc. | Marcadores de expresión génica de la resistencia tumoral al tratamiento con inhibidor de HER2 |
| CN101723936B (zh) * | 2008-10-27 | 2014-01-15 | 上海睿星基因技术有限公司 | 激酶抑制剂及其在药学中的用途 |
| JP5918693B2 (ja) * | 2009-05-05 | 2016-05-18 | ダナ ファーバー キャンサー インスティテュート インコーポレイテッド | Ｅｇｆｒ阻害剤及び疾患の治療方法 |
| US8563567B2 (en) * | 2009-12-30 | 2013-10-22 | Arqule, Inc. | Substituted heterocyclic compounds |
-
2015
- 2015-05-13 JP JP2016567502A patent/JP6468611B2/ja not_active Expired - Fee Related
- 2015-05-13 CN CN201580037958.0A patent/CN106687457B/zh not_active Expired - Fee Related
- 2015-05-13 WO PCT/US2015/030522 patent/WO2015175632A1/en not_active Ceased
- 2015-05-13 EP EP15792086.9A patent/EP3143015B1/en active Active
- 2015-05-13 US US15/310,349 patent/US20170166598A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009158571A1 (en) * | 2008-06-27 | 2009-12-30 | Avila Therapeutics And Uses Thereof | Heteroaryl compounds and uses thereof |
| WO2013014448A1 (en) * | 2011-07-27 | 2013-01-31 | Astrazeneca Ab | 2 - (2, 4, 5 - substituted -anilino) pyrimidine derivatives as egfr modulators useful for treating cancer |
Non-Patent Citations (1)
| Title |
|---|
| Structure- and Reactivity-Based Development of Covalent Inhibitors of the Activating and Gatekeeper Mutant Forms of the Epidermal Growth Factor Receptor (EGFR);Richard A. Ward,et al.;《Journal of Medicinal Chemistry》;20130809;第56卷;第7025-7048页 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12466825B2 (en) | 2019-11-14 | 2025-11-11 | Amgen Inc. | Synthesis of KRAS G12C inhibitor compound |
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| EP3143015A1 (en) | 2017-03-22 |
| EP3143015B1 (en) | 2019-02-20 |
| WO2015175632A1 (en) | 2015-11-19 |
| CN106687457A (zh) | 2017-05-17 |
| JP6468611B2 (ja) | 2019-02-13 |
| US20170166598A1 (en) | 2017-06-15 |
| JP2017518282A (ja) | 2017-07-06 |
| EP3143015A4 (en) | 2017-11-01 |
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