JP6591532B2 - ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体 - Google Patents
ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体 Download PDFInfo
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- JP6591532B2 JP6591532B2 JP2017510290A JP2017510290A JP6591532B2 JP 6591532 B2 JP6591532 B2 JP 6591532B2 JP 2017510290 A JP2017510290 A JP 2017510290A JP 2017510290 A JP2017510290 A JP 2017510290A JP 6591532 B2 JP6591532 B2 JP 6591532B2
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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
- C07D498/22—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 four or more hetero rings
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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
- C07D498/20—Spiro-condensed systems
-
- 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
- A61K31/435—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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- 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
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/20—Spiro-condensed systems
-
- 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
- C07D471/22—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 systems contains four or more hetero rings
-
- 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
- C07D487/10—Spiro-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
- C07D487/12—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 three hetero rings
- C07D487/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Polymers & Plastics (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14181746.0 | 2014-08-21 | ||
| EP14181746 | 2014-08-21 | ||
| PCT/EP2015/069174 WO2016026937A1 (en) | 2014-08-21 | 2015-08-20 | New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017524025A JP2017524025A (ja) | 2017-08-24 |
| JP2017524025A5 JP2017524025A5 (enExample) | 2018-09-27 |
| JP6591532B2 true JP6591532B2 (ja) | 2019-10-16 |
Family
ID=51359320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017510290A Active JP6591532B2 (ja) | 2014-08-21 | 2015-08-20 | ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体 |
Country Status (26)
| Country | Link |
|---|---|
| US (5) | US10246467B2 (enExample) |
| EP (1) | EP3183254B1 (enExample) |
| JP (1) | JP6591532B2 (enExample) |
| KR (2) | KR102627097B1 (enExample) |
| CN (1) | CN107001385B (enExample) |
| AR (1) | AR101600A1 (enExample) |
| AU (1) | AU2015306128B2 (enExample) |
| BR (1) | BR112017002942B1 (enExample) |
| CA (1) | CA2956129C (enExample) |
| CL (1) | CL2017000381A1 (enExample) |
| CY (1) | CY1122127T1 (enExample) |
| DK (1) | DK3183254T3 (enExample) |
| EA (1) | EA038071B1 (enExample) |
| ES (1) | ES2739697T3 (enExample) |
| HR (1) | HRP20191414T1 (enExample) |
| HU (1) | HUE046057T2 (enExample) |
| IL (1) | IL250280B (enExample) |
| LT (1) | LT3183254T (enExample) |
| MX (1) | MX373033B (enExample) |
| PH (1) | PH12017500252A1 (enExample) |
| PL (1) | PL3183254T3 (enExample) |
| PT (1) | PT3183254T (enExample) |
| RS (1) | RS59111B1 (enExample) |
| SI (1) | SI3183254T1 (enExample) |
| TW (1) | TW201625617A (enExample) |
| WO (1) | WO2016026937A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015155332A1 (en) | 2014-04-11 | 2015-10-15 | Boehringer Ingelheim International Gmbh | Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors |
| JP6503386B2 (ja) | 2014-07-03 | 2019-04-17 | 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 | ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体 |
| EA038071B1 (ru) | 2014-08-21 | 2021-07-01 | Бёрингер Ингельхайм Интернациональ Гмбх | СОЕДИНЕНИЕ СПИРО[3H-ИНДОЛ-3,2'-ПИРРОЛИДИН]-2(1H)-ОНА И ЕГО ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ MDM2-p53 |
| NO2721710T3 (enExample) | 2014-08-21 | 2018-03-31 | ||
| PT3359542T (pt) * | 2015-10-09 | 2021-05-25 | Boehringer Ingelheim Int | Compostos de espiro[3h-indole-3,2¿-pirrolidin]-2(1h)-ona e derivados como inibidores de mdm2-p53 |
| CN113788818A (zh) | 2016-04-06 | 2021-12-14 | 密执安大学评议会 | Mdm2蛋白质降解剂 |
| ES2858151T3 (es) | 2016-05-20 | 2021-09-29 | Hoffmann La Roche | Conjugados de PROTAC-anticuerpo y procedimientos de uso |
| EP3606556A1 (en) | 2017-04-05 | 2020-02-12 | Boehringer Ingelheim International GmbH | Anticancer combination therapy |
| CN107290543A (zh) * | 2017-05-02 | 2017-10-24 | 南方医科大学 | 一种检测细胞内与p53转录激活域相互作用蛋白的方法 |
| EP3511334A1 (en) * | 2018-01-16 | 2019-07-17 | Adamed sp. z o.o. | 1,2,3',5'-tetrahydro-2'h-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrole]-2,3'-dione compounds as therapeutic agents activating tp53 |
| JP2020193181A (ja) * | 2019-05-30 | 2020-12-03 | 東ソー株式会社 | 芳香族ニトリル化合物の製造方法 |
| BR112021026559A2 (pt) * | 2019-07-17 | 2022-02-15 | Noxopharm Ltd | Terapia imuno-oncológica usando compostos isoflavona |
| IL298633A (en) | 2020-06-02 | 2023-01-01 | Boehringer Ingelheim Int | Cyclic 2-amino-3-cyanothiophenes and their implications for cancer therapy |
| CN116583275A (zh) * | 2020-09-21 | 2023-08-11 | 诺华股份有限公司 | 用于治疗或预防造血细胞移植后血液肿瘤复发的mdm2抑制剂 |
| CN112375086A (zh) * | 2020-12-11 | 2021-02-19 | 浙江工业大学 | 一种手性螺[呋喃-3,3′-假吲哚]-2-酮类化合物的制备方法 |
| RU2770902C1 (ru) * | 2021-05-24 | 2022-04-25 | Федеральное государственное автономное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" (ПГНИУ) | 3-Арил-6H-спиро[бензо[b]фуро[3',4':2,3]пирроло[1,2-d][1,4]оксазин 5,3'-индолин]-1,2,2',6-тетраоны, обладающие противовоспалительной активностью, и способ их получения |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| US20250129096A1 (en) | 2021-12-01 | 2025-04-24 | Boehringer Ingelheim Int'l GmbH Corp. | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| EP4441056A1 (en) | 2021-12-01 | 2024-10-09 | Boehringer Ingelheim International GmbH | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| WO2023099620A1 (en) | 2021-12-01 | 2023-06-08 | Boehringer Ingelheim International Gmbh | Kras degrading compounds comprising annulated 2-amino-3-cyano thiophenes |
| US20250313553A1 (en) | 2021-12-01 | 2025-10-09 | Boehringer Ingelheim Int'l GmbH Corp. | Annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
| KR20240128852A (ko) | 2021-12-01 | 2024-08-27 | 베링거 인겔하임 인터내셔날 게엠베하 | 암 치료를 위한 고리형 2-아미노-3-시아노 티오펜 및 유도체 |
| CN114831991B (zh) * | 2022-06-10 | 2024-02-06 | 陕西科技大学 | Gsk2334470用于制备抗真菌药物及其增效剂的应用 |
| US11944604B1 (en) | 2023-03-10 | 2024-04-02 | King Saud University | Nanoformulation of spriooxindole and methods for treating hepatocellular carcinoma |
| WO2024240858A1 (en) | 2023-05-23 | 2024-11-28 | Valerio Therapeutics | Protac molecules directed against dna damage repair system and uses thereof |
| TW202511268A (zh) | 2023-05-30 | 2025-03-16 | 德商百靈佳殷格翰國際股份有限公司 | 用於治療癌症之螺環狀2-胺基-3-氰基噻吩及衍生物 |
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| US8680132B2 (en) | 2010-11-12 | 2014-03-25 | The Regents Of The University Of Michigan | Spiro-oxindole MDM2 antagonists |
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| US8629141B2 (en) | 2011-05-11 | 2014-01-14 | The Regents Of The University Of Michigan | Spiro-oxindole MDM2 antagonists |
| CN102443004A (zh) | 2011-11-01 | 2012-05-09 | 南京工业大学 | 有机发光材料6,7,14,15-四氢-5,13-二取代苯并[1,2-c:4,5-c’]二吖啶类化合物、合成方法及应用 |
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