BR122019005502B1 - Compostos de imidazolonilquinolinas, seus usos, composições farmacêuticas, e kit - Google Patents
Compostos de imidazolonilquinolinas, seus usos, composições farmacêuticas, e kit Download PDFInfo
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- BR122019005502B1 BR122019005502B1 BR122019005502-5A BR122019005502A BR122019005502B1 BR 122019005502 B1 BR122019005502 B1 BR 122019005502B1 BR 122019005502 A BR122019005502 A BR 122019005502A BR 122019005502 B1 BR122019005502 B1 BR 122019005502B1
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- methyl
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- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
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- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
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- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
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- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
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- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
- A61K31/435—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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- 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
- C07D471/04—Ortho-condensed systems
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- 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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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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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
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- A61P35/04—Antineoplastic agents specific for metastasis
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- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (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 (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15000968.6 | 2015-04-02 | ||
| EP15000968 | 2015-04-02 | ||
| BR112017020941-1A BR112017020941B1 (pt) | 2015-04-02 | 2016-03-31 | Imidazolonilquinolinas, seus usos, composições farmacêuticas, e kit |
| 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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| BR122019005502B1 true BR122019005502B1 (pt) | 2024-02-27 |
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| BR122019005502-5A BR122019005502B1 (pt) | 2015-04-02 | 2016-03-31 | Compostos de imidazolonilquinolinas, seus usos, composições farmacêuticas, e kit |
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| AU (4) | AU2016239270B2 (https=) |
| BR (1) | BR122019005502B1 (https=) |
| DK (2) | DK3277681T3 (https=) |
| ES (3) | ES2880626T3 (https=) |
| HR (2) | HRP20191396T1 (https=) |
| HU (2) | HUE054745T2 (https=) |
| IL (3) | IL254714B (https=) |
| LT (2) | LT3277681T (https=) |
| MX (2) | MX390537B (https=) |
| PL (2) | PL3560924T3 (https=) |
| PT (2) | PT3277681T (https=) |
| RS (2) | RS62082B1 (https=) |
| RU (1) | RU2743343C2 (https=) |
| SG (2) | SG10202002181UA (https=) |
| SI (2) | SI3277681T1 (https=) |
| TR (1) | TR201911244T4 (https=) |
| WO (1) | WO2016155884A1 (https=) |
| ZA (1) | ZA201707423B (https=) |
Families Citing this family (40)
| 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 |
| CN110312717B (zh) * | 2017-02-27 | 2022-04-12 | 上海瑛派药业有限公司 | 取代的稠合杂芳三环化合物作为激酶抑制剂及其应用 |
| JOP20190209A1 (ar) * | 2017-03-16 | 2019-09-12 | Astrazeneca Ab | مركبات إيميدازو [ 4، 5-c ] كينولين-2-أون ديوترومية واستخدامها في علاج السرطان |
| MX2020007442A (es) | 2018-01-12 | 2020-09-14 | Prolynx Llc | Protocolo para minimizar la toxicidad de dosificaciones de combinacion y agente formador de imagen para verificacion. |
| EP3765019A1 (en) | 2018-03-14 | 2021-01-20 | Merck Patent GmbH | Compounds and uses thereof to treat tumors in a subject |
| FI3904350T3 (fi) | 2018-04-12 | 2023-11-15 | Bayer Ag | N-(syklopropyylimetyyli)-5-(metyylisulfonyyli)-n-{1-[1-(pyrimidin-2-yyli)-1h-1,2,4-triatsol-5-yyli]etyyli}bentsamidijohdannaisia ja vastaavia pyridiinikarboksamidijohdannaisia tuholaistorjunta-aineina |
| 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 |
| CN112771045B (zh) * | 2018-09-30 | 2022-04-19 | 南京明德新药研发有限公司 | 喹啉并吡咯烷-2-酮类衍生物及其应用 |
| RS65518B1 (sr) | 2019-03-27 | 2024-06-28 | Merck Patent Gmbh | Jedinjenja imidazolonilhinolina i njihova terapijska upotreba |
| ES3008232T3 (en) * | 2019-07-30 | 2025-03-21 | Xrad Therapeutics Inc | Dual atm and dna-pk inhibitors for use in anti-tumor therapy |
| WO2021084124A1 (en) | 2019-11-01 | 2021-05-06 | Ares Trading S.A. | COMBINED INHIBITION OF PD-1, TGFβ AND ATM TOGETHER WITH RADIOTHERAPY FOR THE TREATMENT OF CANCER |
| JP7727627B2 (ja) * | 2019-12-04 | 2025-08-21 | シーエイチディーアイ ファウンデーション，インコーポレーテッド | Ａｔｍキナーゼ阻害剤及び組成物並びにそれらの使用の方法 |
| 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 |
| CN115380031A (zh) * | 2020-03-30 | 2022-11-22 | 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 |
| US20230256110A1 (en) | 2020-06-24 | 2023-08-17 | Astrazeneca Uk Limited | Combination of antibody-drug conjugate and atm inhibitor |
| MX2023002792A (es) | 2020-09-18 | 2023-03-16 | Merck Patent Gmbh | Preparacion farmaceutica. |
| EP4142710B1 (en) | 2020-09-21 | 2024-01-31 | Wei Zhong | Substituted 1-(3,3-difluoropiperidin-4-yl)-imidazo[4,5-c] quinolin-2-one compounds with blood-brain barrier penetrable capability |
| 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 |
| AU2023385854A1 (en) | 2022-11-23 | 2025-06-12 | Forward Therapeutics, Inc. | MODULATORS OF TNF-α ACTIVITY |
| 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 |
| WO2025212627A1 (en) | 2024-04-03 | 2025-10-09 | Forward Therapeutics, Inc. | Modulators of tnf-alpha activity |
| WO2025217307A1 (en) | 2024-04-09 | 2025-10-16 | Revolution Medicines, Inc. | Methods for predicting response to a ras(on) inhibitor and combination therapies |
| 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 |
| WO2026015796A1 (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 |
| 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 |
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 |
| PL1879893T3 (pl) | 2005-03-21 | 2010-11-30 | Ferrer Int | Sposób otrzymywania podstawionych w pozycji 1, związków 1H-imidazo[4,5-c]chinolino-4-aminowych i związki pośrednie |
| 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 |
| AU2008218806B2 (en) | 2007-02-20 | 2011-12-01 | Novartis Ag | Imidazoquinolines as dual lipid kinase and mTOR inhibitors |
| KR20100126553A (ko) | 2008-03-26 | 2010-12-01 | 노파르티스 아게 | Ｖｅｇｆ-유도성 혈관신생 과정의 유력한 조절제로서의 이미다조퀴놀린 및 피리미딘 유도체 |
| CN104592231A (zh) | 2008-06-10 | 2015-05-06 | Abbvie公司 | 新的三环化合物 |
| CN102170873B (zh) | 2008-10-01 | 2014-07-30 | 诺华股份有限公司 | 用于治疗与hedgehog通路有关的病症的smoothened拮抗 |
| JP2012528829A (ja) | 2009-06-04 | 2012-11-15 | ノバルティス アーゲー | １Ｈ−イミダゾ［４，５−ｃ］キノリノン化合物 |
| AU2010255727B2 (en) * | 2009-06-04 | 2013-02-28 | Novartis Ag | 1H-imidazo[4,5-c]quinolinone derivatives |
| GB0919423D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| BR112012022868A2 (pt) * | 2010-03-16 | 2018-06-05 | Merck Patent Gmbh | morfolinilquinazolinas |
| AU2011273931B2 (en) * | 2010-06-28 | 2015-04-23 | Merck Patent Gmbh | 2,4- diaryl - substituted [1,8] naphthyridines as kinase inhibitors for use against cancer |
| 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 |
| WO2012075253A2 (en) | 2010-12-03 | 2012-06-07 | 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 |
| US9879003B2 (en) | 2012-04-11 | 2018-01-30 | Dana-Farber Cancer Institute, Inc. | Host targeted inhibitors of dengue virus and other viruses |
| RU2014154009A (ru) | 2012-06-06 | 2016-08-10 | Новартис Аг | Комбинация ингибитора 17-альфа-гидроксилазы (с17,20-лиазы) и специфического ингибитора pi-3k для лечения онкологического заболевания |
| NO2714752T3 (https=) * | 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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