KR20190034225A - 거대환 키나제 억제제 - Google Patents
거대환 키나제 억제제 Download PDFInfo
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- KR20190034225A KR20190034225A KR1020197003927A KR20197003927A KR20190034225A KR 20190034225 A KR20190034225 A KR 20190034225A KR 1020197003927 A KR1020197003927 A KR 1020197003927A KR 20197003927 A KR20197003927 A KR 20197003927A KR 20190034225 A KR20190034225 A KR 20190034225A
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- alkyl
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Classifications
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- 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
- C07D498/12—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 three hetero rings
- C07D498/18—Bridged systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662367886P | 2016-07-28 | 2016-07-28 | |
| US62/367,886 | 2016-07-28 | ||
| PCT/US2017/044214 WO2018022911A1 (en) | 2016-07-28 | 2017-07-27 | Macrocycle kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20190034225A true KR20190034225A (ko) | 2019-04-01 |
Family
ID=61016718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197003927A Ceased KR20190034225A (ko) | 2016-07-28 | 2017-07-27 | 거대환 키나제 억제제 |
Country Status (15)
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Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2933350T3 (es) | 2014-01-24 | 2023-02-06 | Turning Point Therapeutics Inc | Macrociclos de diarilo como moduladores de proteína quinasas |
| AU2016287568B2 (en) | 2015-07-02 | 2020-08-20 | Turning Point Therapeutics, Inc. | Chiral diaryl macrocycles as modulators of protein kinases |
| PT3733187T (pt) | 2015-07-21 | 2024-11-08 | Turning Point Therapeutics Inc | Macrociclo de diarilo quiral e utilização do mesmo no tratamento do cancro |
| US10689400B2 (en) | 2016-07-28 | 2020-06-23 | Turning Point Therapeutics, Inc. | Macrocycle kinase inhibitors |
| TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
| CN111182903A (zh) | 2017-07-28 | 2020-05-19 | 特普医药公司 | 巨环化合物及其用途 |
| CN109516999B (zh) * | 2017-11-01 | 2021-08-17 | 郑州泰基鸿诺医药股份有限公司 | 用作蛋白质激酶调节剂的化合物及其应用 |
| LT3728271T (lt) | 2017-12-19 | 2022-12-12 | Turning Point Therapeutics, Inc. | Makrocikliniai junginiai, skirti ligų gydymui |
| WO2019184955A1 (en) | 2018-03-28 | 2019-10-03 | Fochon Pharmaceuticals, Ltd. | Macrocyclic compounds as trk kinases inhibitors |
| CN111902417B (zh) | 2018-04-25 | 2023-07-28 | 北京普祺医药科技股份有限公司 | 一种二芳基巨环化合物、药物组合物以及其用途 |
| CN117285467A (zh) | 2018-07-31 | 2023-12-26 | 罗索肿瘤学公司 | 喷雾干燥的分散体和制剂 |
| JP7631193B2 (ja) | 2018-10-22 | 2025-02-18 | アルミス インコーポレイテッド | Ｔｙｋ２阻害剤およびその使用 |
| CA3134814A1 (en) * | 2019-03-26 | 2020-10-01 | Ventyx Biosciences, Inc. | Tyk2 pseudokinase ligands |
| WO2020233645A1 (zh) * | 2019-05-21 | 2020-11-26 | 浙江海正药业股份有限公司 | 大环类衍生物、及其制备方法和用途 |
| CN112110938B (zh) * | 2019-06-21 | 2021-11-09 | 成都海博为药业有限公司 | 一种作为蛋白质激酶抑制剂的化合物及其制备方法和用途 |
| WO2021027503A1 (zh) * | 2019-08-12 | 2021-02-18 | 罗欣药业(上海)有限公司 | 三环类化合物、其制备方法、中间体及应用 |
| US20220372135A1 (en) | 2019-09-27 | 2022-11-24 | Disc Medicine, Inc. | Methods for treating myelofibrosis and related conditions |
| EP4114530A4 (en) * | 2020-03-02 | 2024-04-17 | Turning Point Therapeutics, Inc. | THERAPEUTIC USES OF MACROCYCLIC COMPOUNDS |
| KR20230012539A (ko) | 2020-05-13 | 2023-01-26 | 디스크 메디슨, 인크. | 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체 |
| EP4163283A1 (en) * | 2020-06-04 | 2023-04-12 | Scinnohub Pharmaceutical Co., Ltd | Compound having macrocyclic structure and use thereof |
| US20240132517A1 (en) * | 2021-02-10 | 2024-04-25 | Goharmony Therapeutics (Shenzhen) Co., Ltd. | Macrocyclic compound, pharmaceutical composition, and use thereof |
| CN113354548A (zh) * | 2021-04-12 | 2021-09-07 | 常熟耐素生物材料科技有限公司 | 一种基于六亚甲基四胺的植物多烯酚醛胺环氧固化剂及其制备方法 |
| CN116063326B (zh) * | 2021-11-02 | 2025-08-05 | 赛诺哈勃药业（成都）有限公司 | 作为蛋白激酶调节剂的含氨基大环化合物 |
| WO2023208244A1 (zh) * | 2022-04-29 | 2023-11-02 | 南京明德新药研发有限公司 | 大环类化合物及其应用 |
| WO2025010294A2 (en) * | 2023-07-03 | 2025-01-09 | Blossomhill Therapeutics, Inc. | Macrocyclic compounds and use as tyk2 inhibitors |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE195935T1 (de) | 1993-03-25 | 2000-09-15 | Upjohn Co | Formyl- oder cyano- substituierte indolderivate mit dopaminergischer wirkung |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
| KR20110073500A (ko) | 2008-09-08 | 2011-06-29 | 메르크 파텐트 게엠베하 | 오로라 키나아제 억제제로서 마크로사이클릭 피리미딘 |
| WO2010033941A1 (en) | 2008-09-22 | 2010-03-25 | Array Biopharma Inc. | Substituted imidazo[1,2b]pyridazine compounds as trk kinase inhibitors |
| MY169791A (en) | 2008-10-22 | 2019-05-15 | Array Biopharma Inc | Substituted pyrazolo [1,5-a] pyrimidine compounds as trk kinase inhibitors |
| EP2348860B1 (en) | 2008-10-31 | 2015-05-27 | Genentech, Inc. | Pyrazolopyrimidine jak inhibitor compounds and methods |
| ME03376B (me) | 2010-05-20 | 2020-01-20 | Array Biopharma Inc | Makrociklička jedinjenja kао inhibiтori trk kinaze |
| US8757434B2 (en) * | 2010-07-01 | 2014-06-24 | The Coca-Cola Company | Merchandiser |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| EP2508607A1 (en) | 2011-04-07 | 2012-10-10 | Helmholtz-Zentrum für Infektionsforschung GmbH | Medicament for liver regeneration and for treatment of liver failure |
| PL2710018T3 (pl) * | 2011-05-19 | 2022-04-04 | Fundación Del Sector Público Estatal Centro Nacional De Investigaciones Oncológicas Carlos III (F.S.P. CNIO) | Związki makrocykliczne jako inhibitory kinaz białkowych |
| WO2013001310A1 (en) | 2011-06-30 | 2013-01-03 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Macrocyclic compounds and their use as cdk8 inhibitors |
| BR112014003802A2 (pt) | 2011-08-19 | 2017-06-13 | Merck Sharp & Dohme | composto, composto composição farmacêutica, uso de um composto, método para fabricar um composto, e, preparação de um medicamento |
| BR112014007622A2 (pt) | 2011-09-30 | 2017-04-04 | Oncodesign Sa | inibidores de flt3 cinase macrocíclicos |
| HUE029728T2 (en) * | 2011-09-30 | 2017-03-28 | Ipsen Pharma Sas | Macrocyclic LRRK2 kinase inhibitors |
| DK2822953T5 (en) | 2012-03-06 | 2017-09-11 | Pfizer | Macrocyclic derivatives for the treatment of proliferative diseases |
| WO2013134219A1 (en) | 2012-03-09 | 2013-09-12 | Lexicon Pharmaceuticals, Inc. | Imidazo [1, 2 - b] pyridazine - based compounds, compositions comprising them, and uses thereof |
| CN104302649B (zh) | 2012-03-09 | 2017-06-23 | 莱西肯医药有限公司 | 基于吡唑并[1,5‑a]嘧啶的化合物、包含它们的组合物及其使用方法 |
| GB201205669D0 (en) | 2012-03-30 | 2012-05-16 | Agency Science Tech & Res | Bicyclic heterocyclic derivatives as mnk2 and mnk2 modulators and uses thereof |
| EA201591773A1 (ru) * | 2013-03-15 | 2016-01-29 | Онкодизайн С.А. | Макроциклические ингибиторы rip2-киназы |
| CN104513253A (zh) * | 2013-10-01 | 2015-04-15 | 南京波尔泰药业科技有限公司 | 用于治疗增殖性疾病的大环化合物 |
| ES2933350T3 (es) | 2014-01-24 | 2023-02-06 | Turning Point Therapeutics Inc | Macrociclos de diarilo como moduladores de proteína quinasas |
| AU2016287568B2 (en) * | 2015-07-02 | 2020-08-20 | Turning Point Therapeutics, Inc. | Chiral diaryl macrocycles as modulators of protein kinases |
| RU2765181C2 (ru) | 2015-07-06 | 2022-01-26 | Тёрнинг Поинт Терапьютикс, Инк. | Полиморфная форма диарильного макроцикла |
| PT3733187T (pt) | 2015-07-21 | 2024-11-08 | Turning Point Therapeutics Inc | Macrociclo de diarilo quiral e utilização do mesmo no tratamento do cancro |
| US10689400B2 (en) | 2016-07-28 | 2020-06-23 | Turning Point Therapeutics, Inc. | Macrocycle kinase inhibitors |
| TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
| CN111182903A (zh) | 2017-07-28 | 2020-05-19 | 特普医药公司 | 巨环化合物及其用途 |
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2017
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- 2017-07-27 MX MX2019001125A patent/MX2019001125A/es unknown
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| BR112019001607A2 (pt) | 2019-04-30 |
| EP3490564A4 (en) | 2020-02-26 |
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| IL264395A (en) | 2019-02-28 |
| ZA201901034B (en) | 2021-06-30 |
| RU2019105587A (ru) | 2020-08-28 |
| TW201815799A (zh) | 2018-05-01 |
| JP2019527230A (ja) | 2019-09-26 |
| US10689400B2 (en) | 2020-06-23 |
| CA3031100A1 (en) | 2018-02-01 |
| MX2019001125A (es) | 2019-06-12 |
| AU2017302019A1 (en) | 2019-02-07 |
| RU2019105587A3 (https=) | 2020-11-18 |
| SG11201900163PA (en) | 2019-02-27 |
| WO2018022911A1 (en) | 2018-02-01 |
| EP3490564A1 (en) | 2019-06-05 |
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