JP2017510610A5 - - Google Patents
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- Publication number
- JP2017510610A5 JP2017510610A5 JP2016561754A JP2016561754A JP2017510610A5 JP 2017510610 A5 JP2017510610 A5 JP 2017510610A5 JP 2016561754 A JP2016561754 A JP 2016561754A JP 2016561754 A JP2016561754 A JP 2016561754A JP 2017510610 A5 JP2017510610 A5 JP 2017510610A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- independently
- hydrogen
- aryl
- cycloalkyl
- 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 43
- 229910052739 hydrogen Inorganic materials 0.000 claims 31
- 239000001257 hydrogen Substances 0.000 claims 31
- 125000003118 aryl group Chemical group 0.000 claims 24
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 21
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 21
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims 18
- 229910052736 halogen Inorganic materials 0.000 claims 18
- 150000002367 halogens Chemical class 0.000 claims 18
- 150000003839 salts Chemical class 0.000 claims 18
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 16
- 150000001875 compounds Chemical class 0.000 claims 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 15
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 15
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 12
- 150000002431 hydrogen Chemical class 0.000 claims 11
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 239000000543 intermediate Substances 0.000 claims 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 3
- 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
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 claims 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
- 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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 229910052717 sulfur Chemical group 0.000 claims 1
- 239000011593 sulfur Chemical group 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14164388.2 | 2014-04-11 | ||
| EP14164388 | 2014-04-11 | ||
| PCT/EP2015/057839 WO2015155332A1 (en) | 2014-04-11 | 2015-04-10 | Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017510610A JP2017510610A (ja) | 2017-04-13 |
| JP2017510610A5 true JP2017510610A5 (enExample) | 2018-05-31 |
| JP6577958B2 JP6577958B2 (ja) | 2019-09-18 |
Family
ID=50478306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016561754A Active JP6577958B2 (ja) | 2014-04-11 | 2015-04-10 | スピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン誘導体およびＭＤＭ２−ｐ５３阻害剤としてのそれらの使用 |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US10138251B2 (enExample) |
| EP (1) | EP3129380B1 (enExample) |
| JP (1) | JP6577958B2 (enExample) |
| WO (1) | WO2015155332A1 (enExample) |
Families Citing this family (20)
| 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 |
| 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 |
| US11339171B2 (en) * | 2017-12-29 | 2022-05-24 | Gan & Lee Pharmaceuticals | MDM2 inhibitors |
| WO2020018611A1 (en) * | 2018-07-18 | 2020-01-23 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment, prevention, and treatment of ewing sarcoma using tp53 dependency biomarkers and modulators |
| IL298633A (en) | 2020-06-02 | 2023-01-01 | Boehringer Ingelheim Int | Cyclic 2-amino-3-cyanothiophenes and their implications for cancer therapy |
| US11351149B2 (en) | 2020-09-03 | 2022-06-07 | Pfizer Inc. | Nitrile-containing antiviral compounds |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| 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 |
| 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 |
| 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 |
| WO2024078370A1 (zh) * | 2022-10-13 | 2024-04-18 | 中国科学院上海药物研究所 | 具有取代苯基螺[吲哚啉-3,3'-吡咯烷]结构的小分子化合物 |
| 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 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1012270A2 (en) | 1997-09-12 | 2000-06-28 | Apotech R&D S.A. | Kay - a novel immune system protein |
| AR073578A1 (es) | 2008-09-15 | 2010-11-17 | Priaxon Ag | Pirrolidin-2-onas |
| 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 |
| 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 |
| US8629141B2 (en) * | 2011-05-11 | 2014-01-14 | The Regents Of The University Of Michigan | Spiro-oxindole MDM2 antagonists |
| 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 |
| 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 |
| NO2721710T3 (enExample) | 2014-08-21 | 2018-03-31 | ||
| 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 |
| 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 |
-
2015
- 2015-04-10 WO PCT/EP2015/057839 patent/WO2015155332A1/en not_active Ceased
- 2015-04-10 EP EP15716495.5A patent/EP3129380B1/en active Active
- 2015-04-10 JP JP2016561754A patent/JP6577958B2/ja active Active
- 2015-04-10 US US14/683,173 patent/US10138251B2/en active Active
-
2018
- 2018-06-11 US US16/005,316 patent/US20180291030A1/en not_active Abandoned