JP2017524025A5 - - Google Patents
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- JP2017524025A5 JP2017524025A5 JP2017510290A JP2017510290A JP2017524025A5 JP 2017524025 A5 JP2017524025 A5 JP 2017524025A5 JP 2017510290 A JP2017510290 A JP 2017510290A JP 2017510290 A JP2017510290 A JP 2017510290A JP 2017524025 A5 JP2017524025 A5 JP 2017524025A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- independently
- haloalkyl
- salt
- aryl
- 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.)
- Granted
Links
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims description 31
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 31
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 28
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 25
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 14
- 239000008194 pharmaceutical composition Substances 0.000 claims 7
- 239000000543 intermediate Substances 0.000 claims 5
- 239000013543 active substance Substances 0.000 claims 3
- 239000000824 cytostatic agent Substances 0.000 claims 3
- 230000001085 cytostatic effect Effects 0.000 claims 3
- 231100000433 cytotoxic Toxicity 0.000 claims 3
- 230000001472 cytotoxic effect Effects 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 claims 1
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 150000001414 amino alcohols Chemical class 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000001376 precipitating effect Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 229910052717 sulfur Chemical group 0.000 claims 1
- 239000011593 sulfur Chemical group 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
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 true JP2017524025A5 (enExample) | 2018-09-27 |
| JP6591532B2 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) | US20160052938A1 (enExample) |
| EP (1) | EP3183254B1 (enExample) |
| JP (1) | JP6591532B2 (enExample) |
| KR (2) | KR20170042779A (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) | PH12017500252B1 (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 |
|---|---|---|---|---|
| US10138251B2 (en) | 2014-04-11 | 2018-11-27 | Boehringer Ingelheim International Gmbh | Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives 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 |
| NO2721710T3 (enExample) | 2014-08-21 | 2018-03-31 | ||
| MX373033B (es) * | 2014-08-21 | 2020-05-27 | Boehringer Ingelheim Int | Nuevos compuestos de espiro[3h-indol-3,2´-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53. |
| EP3359542B1 (en) | 2015-10-09 | 2021-03-17 | Boehringer Ingelheim International GmbH | Spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
| CN113788818A (zh) | 2016-04-06 | 2021-12-14 | 密执安大学评议会 | Mdm2蛋白质降解剂 |
| CN118436801A (zh) | 2016-05-20 | 2024-08-06 | 豪夫迈·罗氏有限公司 | Protac抗体缀合物及其使用方法 |
| BR112019021032A2 (pt) | 2017-04-05 | 2020-05-05 | Boehringer Ingelheim International Gmbh | terapia combinada anticâncer |
| 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 |
| KR20220035038A (ko) * | 2019-07-17 | 2022-03-21 | 녹소팜 리미티드 | 이소플라본 화합물을 사용하는 면역종양학 요법 |
| BR112022023462A2 (pt) | 2020-06-02 | 2022-12-20 | Boehringer Ingelheim Int | 2-amino-3-ciano tiofenos anulados e derivados para o tratamento de câncer |
| 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 |
| CN118591540A (zh) | 2021-12-01 | 2024-09-03 | 勃林格殷格翰国际有限公司 | 包含环状2-氨基-3-氰基噻吩的kras降解化合物 |
| US20250129095A1 (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 |
| CN119841847A (zh) | 2021-12-01 | 2025-04-18 | 勃林格殷格翰国际有限公司 | 用于治疗癌症的环状2-氨基-3-氰基噻吩及其衍生物 |
| JP2024543976A (ja) | 2021-12-01 | 2024-11-26 | 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 | 癌の処置のための環化２－アミノ－３－シアノチオフェン及び誘導体 |
| 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 |
| 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 |
| AR132802A1 (es) | 2023-05-30 | 2025-07-30 | Boehringer Ingelheim Int | 2-amino-3-cianotiofenos con anillos espirocíclicos y derivados para el tratamiento del cáncer |
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| US3361759A (en) | 1963-10-07 | 1968-01-02 | Upjohn Co | 3-(2-pyrrolidinyl)-indoles and method of preparation |
| US4219560A (en) | 1978-04-17 | 1980-08-26 | Sandoz, Inc. | Piperidine and pyrrolidine alcohols |
| US5574044A (en) | 1994-10-27 | 1996-11-12 | Merck & Co., Inc. | Muscarine antagonists |
| EP1015430A4 (en) | 1997-09-08 | 2001-01-17 | Arqule Inc | SPIRO (PRROLIDIN-2,3'-OXOINDOL) COMPOUNDS AND METHOD FOR USE THEREOF |
| CA2371618A1 (en) | 1999-04-28 | 2000-11-09 | Yuji Ishihara | Cyclic amide compounds, their production and use |
| EA019566B1 (ru) | 2005-02-22 | 2014-04-30 | Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган | Низкомолекулярные ингибиторы mdm2 |
| JP2006234861A (ja) | 2005-02-22 | 2006-09-07 | Fujinon Sano Kk | 光学ガラスの製造方法，偏光変換素子の製造方法及び偏光変換素子 |
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| EA016145B1 (ru) | 2006-08-30 | 2012-02-28 | Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган | Новые низкомолекулярные ингибиторы mdm2 и их применение |
| AR065860A1 (es) | 2007-03-29 | 2009-07-08 | Novartis Ag | 3-imidazolil-indoles para el tratamiento de enfermedades proliferativas |
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| JO2998B1 (ar) | 2010-06-04 | 2016-09-05 | Amgen Inc | مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان |
| US20120046306A1 (en) | 2010-08-18 | 2012-02-23 | David Joseph Bartkovitz | Substituted Heteroaryl Spiropyrrolidine MDM2 Antagonists |
| US20120071499A1 (en) | 2010-09-20 | 2012-03-22 | Xin-Jie Chu | Substituted Spiro[3H-Indole-3,6'(5'H)-[1H]Pyrrolo[1,2c]Imidazole-1',2(1H,2'H)-diones |
| MX2013005238A (es) | 2010-11-12 | 2013-09-02 | Univ Michigan | Antagonistas de mdm2 de espiro-oxindol. |
| US20130053410A1 (en) * | 2011-03-03 | 2013-02-28 | David Joseph Bartkovitz | Substituted heteroaryl 2',3',7',7a'-tetrahydrospiro[pyrrole-3,6'-pyrrolo[1,2-c]imidazole]-1',2(1h,5'h)-dione |
| DK2684880T3 (en) | 2011-03-10 | 2018-05-22 | Daiichi Sankyo Co Ltd | DISPIROPYRROLIDINE DERIVATIVES |
| JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| BR112013028983A2 (pt) | 2011-05-11 | 2017-02-07 | Sanofi Sa | antagonistas mdm2 espiro-oxindol |
| 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 |
| CN103910746B (zh) | 2014-02-28 | 2016-08-03 | 中山大学 | 一类海洋真菌来源的Berkeleyones化合物及其制备方法和应用 |
| US10138251B2 (en) | 2014-04-11 | 2018-11-27 | Boehringer Ingelheim International Gmbh | Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors |
| MX373045B (es) | 2014-04-17 | 2020-05-26 | Univ Michigan Regents | Inhibidores de mdm2 y metodos terapeuticos que utilizan el mismo. |
| 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 |
| ES2959097T3 (es) | 2014-08-18 | 2024-02-20 | Hudson Biopharma Inc | Espiropirrolidinas como inhibidores de MDM2 |
| MX373033B (es) | 2014-08-21 | 2020-05-27 | Boehringer Ingelheim Int | Nuevos compuestos de espiro[3h-indol-3,2´-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53. |
| NO2721710T3 (enExample) | 2014-08-21 | 2018-03-31 | ||
| EP3359542B1 (en) | 2015-10-09 | 2021-03-17 | Boehringer Ingelheim International GmbH | Spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
| JP6841821B2 (ja) | 2015-10-09 | 2021-03-10 | ノースウェスタン ユニバーシティ | てんかん、嗜癖および肝細胞癌の処置のためのｇａｂａアミノトランスフェラーゼ不活性化剤としての（ｓ）−３−アミノ−４−（ジフルオロメチレニル）シクロペント−１−エン−１−カルボン酸および関連化合物 |
| KR20180083323A (ko) | 2015-10-09 | 2018-07-20 | 애브비 에스.에이.알.엘. | N-설포닐화 피라졸로[3,4-b]피리딘-6-카복스아미드 및 사용 방법 |
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2015
- 2015-08-20 MX MX2017002260A patent/MX373033B/es active IP Right Grant
- 2015-08-20 CN CN201580043566.5A patent/CN107001385B/zh active Active
- 2015-08-20 HR HRP20191414 patent/HRP20191414T1/hr unknown
- 2015-08-20 US US14/831,241 patent/US20160052938A1/en not_active Abandoned
- 2015-08-20 CA CA2956129A patent/CA2956129C/en active Active
- 2015-08-20 EA EA201790425A patent/EA038071B1/ru not_active IP Right Cessation
- 2015-08-20 PL PL15751029T patent/PL3183254T3/pl unknown
- 2015-08-20 LT LTEP15751029.8T patent/LT3183254T/lt unknown
- 2015-08-20 EP EP15751029.8A patent/EP3183254B1/en active Active
- 2015-08-20 ES ES15751029T patent/ES2739697T3/es active Active
- 2015-08-20 AR ARP150102682A patent/AR101600A1/es unknown
- 2015-08-20 JP JP2017510290A patent/JP6591532B2/ja active Active
- 2015-08-20 AU AU2015306128A patent/AU2015306128B2/en active Active
- 2015-08-20 HU HUE15751029A patent/HUE046057T2/hu unknown
- 2015-08-20 KR KR1020177007523A patent/KR20170042779A/ko not_active Abandoned
- 2015-08-20 BR BR112017002942-1A patent/BR112017002942B1/pt active IP Right Grant
- 2015-08-20 PT PT15751029T patent/PT3183254T/pt unknown
- 2015-08-20 KR KR1020237020952A patent/KR102627097B1/ko active Active
- 2015-08-20 RS RS20191048A patent/RS59111B1/sr unknown
- 2015-08-20 SI SI201530811T patent/SI3183254T1/sl unknown
- 2015-08-20 US US15/503,754 patent/US10246467B2/en active Active
- 2015-08-20 WO PCT/EP2015/069174 patent/WO2016026937A1/en not_active Ceased
- 2015-08-20 DK DK15751029.8T patent/DK3183254T3/da active
- 2015-08-21 TW TW104127396A patent/TW201625617A/zh unknown
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2017
- 2017-01-25 IL IL250280A patent/IL250280B/en active IP Right Grant
- 2017-02-10 PH PH12017500252A patent/PH12017500252B1/en unknown
- 2017-02-15 CL CL2017000381A patent/CL2017000381A1/es unknown
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2019
- 2019-02-11 US US16/272,482 patent/US10919913B2/en active Active
- 2019-08-08 CY CY20191100845T patent/CY1122127T1/el unknown
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2020
- 2020-12-11 US US17/118,856 patent/US20210101912A1/en not_active Abandoned
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2023
- 2023-09-08 US US18/463,407 patent/US12312363B2/en active Active