CA2981365A1 - Imidazolonylquinolines and the use thereof as atm kinase inhibitors - Google Patents
Imidazolonylquinolines and the use thereof as atm kinase inhibitors Download PDFInfo
- Publication number
- CA2981365A1 CA2981365A1 CA2981365A CA2981365A CA2981365A1 CA 2981365 A1 CA2981365 A1 CA 2981365A1 CA 2981365 A CA2981365 A CA 2981365A CA 2981365 A CA2981365 A CA 2981365A CA 2981365 A1 CA2981365 A1 CA 2981365A1
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- Prior art keywords
- pyrazol
- methyl
- methoxy
- fluoro
- quinolin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 5
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Classifications
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- 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
- C07D471/04—Ortho-condensed systems
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A—HUMAN NECESSITIES
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- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- 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
- 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
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- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- A—HUMAN NECESSITIES
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- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
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| EP15000968.6 | 2015-04-02 | ||
| EP15000968 | 2015-04-02 | ||
| PCT/EP2016/000542 WO2016155884A1 (de) | 2015-04-02 | 2016-03-31 | Imidazolonylchinoline und deren verwendung als atm kinase inhibitoren |
Publications (1)
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| CA2981365A1 true CA2981365A1 (en) | 2016-10-06 |
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| CA2981365A Pending CA2981365A1 (en) | 2015-04-02 | 2016-03-31 | Imidazolonylquinolines and the use thereof as atm kinase inhibitors |
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| MX (2) | MX376947B (enExample) |
| PL (2) | PL3277681T3 (enExample) |
| PT (2) | PT3277681T (enExample) |
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| WO (1) | WO2016155884A1 (enExample) |
| ZA (1) | ZA201707423B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12344604B2 (en) | 2019-03-27 | 2025-07-01 | Merck Patent Gmbh | Imidazolonylquinoline compounds and therapeutic uses thereof |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS62082B1 (sr) * | 2015-04-02 | 2021-08-31 | Merck Patent Gmbh | Imidazolonilhinolini i njihova primena kao inhibitora atm kinaze |
| GB201516504D0 (en) | 2015-09-17 | 2015-11-04 | Astrazeneca Ab | Imadazo(4,5-c)quinolin-2-one Compounds and their use in treating cancer |
| GB201519406D0 (en) * | 2015-11-03 | 2015-12-16 | Astrazeneca Ab | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
| US11547703B2 (en) | 2017-02-27 | 2023-01-10 | Impact Therapeutics (Shanghai), Inc | Substituted fused heteroaromatic tricyclic compounds as kinase inhibitors and the use thereof |
| JOP20190209A1 (ar) * | 2017-03-16 | 2019-09-12 | Astrazeneca Ab | مركبات إيميدازو [ 4، 5-c ] كينولين-2-أون ديوترومية واستخدامها في علاج السرطان |
| RU2020126774A (ru) | 2018-01-12 | 2022-02-14 | ПРОЛИНКС ЭлЭлСи | Протокол для сведения к минимуму токсического воздействия комбинированных доз и визуализирующий агент для подтверждения |
| CN111867589A (zh) * | 2018-03-14 | 2020-10-30 | 默克专利股份有限公司 | 在对象中治疗肿瘤的化合物及其用途 |
| WO2019197468A1 (en) | 2018-04-12 | 2019-10-17 | Bayer Aktiengesellschaft | N-(cyclopropylmethyl)-5-(methylsulfonyl)-n-{1-[1-(pyrimidin-2-yl)-1h-1,2,4-triazol-5-yl]ethyl}benzamide derivatives and the corresponding pyridine-carboxamide derivatives as pesticides |
| WO2019201283A1 (en) * | 2018-04-20 | 2019-10-24 | Xrad Therapeutics, Inc. | Dual atm and dna-pk inhibitors for use in anti-tumor therapy |
| CN110386932A (zh) * | 2018-04-20 | 2019-10-29 | 艾科思莱德制药公司 | 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂 |
| GB201814487D0 (en) * | 2018-09-06 | 2018-10-24 | Cycle Pharmaceuticals Ltd | Cancer |
| CN109045042A (zh) * | 2018-09-21 | 2018-12-21 | 上海交通大学医学院附属上海儿童医学中心 | Atm抑制剂在制备抑制急性淋巴细胞性白血病复发的药物中的应用 |
| EP3845532B1 (en) * | 2018-09-30 | 2022-12-21 | Medshine Discovery Inc. | Quinolino-pyrrolidin-2-one derivative and application thereof |
| EP4003345B1 (en) * | 2019-07-30 | 2024-12-04 | XRad Therapeutics, Inc. | Dual atm and dna-pk inhibitors for use in anti-tumor therapy |
| AU2020375161A1 (en) * | 2019-11-01 | 2022-05-19 | Ares Trading S.A. | Combined inhibition of PD-1, TGFβ and ATM together with radiotherapy for the treatment of cancer |
| EP4069366B1 (en) * | 2019-12-04 | 2025-03-19 | CHDI Foundation, Inc. | Atm kinase inhibitors and compositions and methods of use thereof |
| WO2021139814A1 (zh) * | 2020-01-09 | 2021-07-15 | 南京明德新药研发有限公司 | 喹啉并咪唑类化合物及其应用 |
| WO2021197339A1 (zh) * | 2020-03-30 | 2021-10-07 | 南京明德新药研发有限公司 | 作为atm抑制剂的喹啉并吡咯烷-2-酮类化合物的晶型及其应用 |
| IL299178A (en) * | 2020-06-18 | 2023-02-01 | Merck Patent Gmbh | Atm inhibitors for use in treatment of viral infections |
| EP4171651A1 (en) | 2020-06-24 | 2023-05-03 | AstraZeneca UK Limited | Combination of antibody-drug conjugate and atm inhibitor |
| JP2023542496A (ja) | 2020-09-18 | 2023-10-10 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 医薬製剤 |
| CN116056698B (zh) * | 2020-09-21 | 2024-11-19 | 威尚（上海）生物医药有限公司 | 具有血脑屏障穿透能力的取代的1-(3,3-二氟哌啶-4-基)-咪唑并[4,5-c]喹啉-2-酮化合物 |
| EP3992191A1 (en) | 2020-11-03 | 2022-05-04 | Deutsches Krebsforschungszentrum | Imidazo[4,5-c]quinoline compounds and their use as atm kinase inhibitors |
| CN115232122B (zh) * | 2021-04-23 | 2024-05-31 | 石药集团中奇制药技术（石家庄）有限公司 | 炔类化合物及其制备和应用 |
| CN115716829B (zh) * | 2022-11-13 | 2024-05-31 | 药康众拓(江苏)医药科技有限公司 | 一种喹啉并咪唑酮联氘代吡唑类化合物及其应用 |
| JP2025540024A (ja) | 2022-11-23 | 2025-12-11 | フォワード セラピューティクス， インコーポレイテッド | ＴＮＦ－α活性の調節因子 |
| WO2025157979A1 (en) | 2024-01-26 | 2025-07-31 | Merck Patent Gmbh | Synthesis route for preparing 8-(1,3-dimethyl-1h-pyrazol-4-yl)-1-(sa)-(3-fluoro-5-methoxy-pyridin-4-yl)-7-methoxy-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one |
| WO2025217307A1 (en) | 2024-04-09 | 2025-10-16 | Revolution Medicines, Inc. | Methods for predicting response to a ras(on) inhibitor and combination therapies |
| 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 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6221335B1 (en) * | 1994-03-25 | 2001-04-24 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| PT1104760E (pt) * | 1999-12-03 | 2003-06-30 | Pfizer Prod Inc | Compostos de sulfamoil-heteroarilpirazole como agentes analgesicos e anti-inflamatorios |
| GB0211649D0 (en) | 2002-05-21 | 2002-07-03 | Novartis Ag | Organic compounds |
| EP1879893B1 (en) | 2005-03-21 | 2010-06-02 | Ferrer Internacional, S.A. | Method for making 1-substituted 1h-imidazo[4,5-c]quinolin-4-amine compounds and intermediates therefor |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| EP1934201A1 (en) * | 2005-10-06 | 2008-06-25 | Auspex Pharmaceuticals Inc. | Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties |
| US7750168B2 (en) * | 2006-02-10 | 2010-07-06 | Sigma-Aldrich Co. | Stabilized deuteroborane-tetrahydrofuran complex |
| EP2129379B1 (en) | 2007-02-20 | 2019-04-10 | Novartis AG | Imidazoquinolines as dual lipid kinase and mtor inhibitors |
| EP2276488A1 (en) | 2008-03-26 | 2011-01-26 | Novartis AG | 5imidazoquinolines and pyrimidine derivatives as potent modulators of vegf-driven angiogenic processes |
| TW201612182A (en) * | 2008-06-10 | 2016-04-01 | Abbvie Inc | Novel tricyclic compounds |
| JP5773873B2 (ja) | 2008-10-01 | 2015-09-02 | ノバルティス アーゲー | ヘッジホッグ経路関連障害の治療のためのスムースンド拮抗作用 |
| KR101445458B1 (ko) * | 2009-06-04 | 2014-10-07 | 노파르티스 아게 | １Ｈ-이미다조［４,５-ｃ］퀴놀리논 유도체 |
| US20100311714A1 (en) | 2009-06-04 | 2010-12-09 | Pascal Furet | 1H-IMIDAZO[4,5-c]QUINOLINONE COMPOUNDS |
| GB0919423D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| AU2011229542A1 (en) * | 2010-03-16 | 2012-11-08 | Merck Patent Gmbh | Morpholinylquinazolines |
| CN102958930B (zh) * | 2010-06-28 | 2018-04-27 | 默克专利有限公司 | 作为用于对抗癌症的激酶抑制剂的2,4-二芳基取代的[1,8]二氮杂萘化合物 |
| CN102372711B (zh) | 2010-08-18 | 2014-09-17 | 山东轩竹医药科技有限公司 | 咪唑并喹啉类PI3K和mTOR双重抑制剂 |
| DE102010035744A1 (de) | 2010-08-28 | 2012-03-01 | Merck Patent Gmbh | Imidazolonylchinoline |
| CN102399218A (zh) * | 2010-09-16 | 2012-04-04 | 和记黄埔医药（上海）有限公司 | 一类并合三杂环及其作为pi3k抑制剂的用途 |
| SG190210A1 (en) | 2010-12-03 | 2013-06-28 | Novartis Ag | Pharmaceutical compositions |
| CN103012398B (zh) | 2011-09-19 | 2015-10-14 | 上海恒瑞医药有限公司 | 咪唑并喹啉类衍生物及其可药用盐、其制备方法及其在医药上的应用 |
| WO2013154778A1 (en) | 2012-04-11 | 2013-10-17 | Dana-Farber Cancer Institute, Inc. | Host targeted inhibitors of dengue virus and other viruses |
| KR20150017367A (ko) | 2012-06-06 | 2015-02-16 | 노파르티스 아게 | 종양 질환을 치료하기 위한 17-알파-히드록실라제 (c17,20-리아제) 억제제와 특이적 pi-3k 억제제의 조합물 |
| NO2714752T3 (enExample) * | 2014-05-08 | 2018-04-21 | ||
| RS62082B1 (sr) | 2015-04-02 | 2021-08-31 | Merck Patent Gmbh | Imidazolonilhinolini i njihova primena kao inhibitora atm kinaze |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12344604B2 (en) | 2019-03-27 | 2025-07-01 | Merck Patent Gmbh | Imidazolonylquinoline compounds and therapeutic uses thereof |
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