JP2017527532A5 - - Google Patents
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- Publication number
- JP2017527532A5 JP2017527532A5 JP2016575738A JP2016575738A JP2017527532A5 JP 2017527532 A5 JP2017527532 A5 JP 2017527532A5 JP 2016575738 A JP2016575738 A JP 2016575738A JP 2016575738 A JP2016575738 A JP 2016575738A JP 2017527532 A5 JP2017527532 A5 JP 2017527532A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- independently
- aryl
- haloalkyl
- salt
- 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 35
- 150000003839 salts Chemical class 0.000 claims 21
- 150000001875 compounds Chemical class 0.000 claims 20
- 125000003118 aryl group Chemical group 0.000 claims 18
- 229910052739 hydrogen Inorganic materials 0.000 claims 18
- 239000001257 hydrogen Substances 0.000 claims 18
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 16
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 15
- 229910052736 halogen Inorganic materials 0.000 claims 15
- 150000002367 halogens Chemical class 0.000 claims 15
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 14
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 12
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 9
- 150000002431 hydrogen Chemical class 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 3
- 208000023275 Autoimmune disease Diseases 0.000 claims 3
- 208000035473 Communicable disease Diseases 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 206010061218 Inflammation Diseases 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 230000004054 inflammatory process Effects 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 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
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 229910052717 sulfur Chemical group 0.000 claims 1
- 239000011593 sulfur Chemical group 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14175620 | 2014-07-03 | ||
| EP14175620.5 | 2014-07-03 | ||
| PCT/EP2015/065134 WO2016001376A1 (en) | 2014-07-03 | 2015-07-02 | New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017527532A JP2017527532A (ja) | 2017-09-21 |
| JP2017527532A5 true JP2017527532A5 (OSRAM) | 2018-08-16 |
| JP6503386B2 JP6503386B2 (ja) | 2019-04-17 |
Family
ID=51033079
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016575738A Active JP6503386B2 (ja) | 2014-07-03 | 2015-07-02 | 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 (4)
| Country | Link |
|---|---|
| US (1) | US10576064B2 (OSRAM) |
| EP (1) | EP3164401B1 (OSRAM) |
| JP (1) | JP6503386B2 (OSRAM) |
| WO (1) | WO2016001376A1 (OSRAM) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3129380B1 (en) | 2014-04-11 | 2018-11-28 | Boehringer Ingelheim International Gmbh | Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors |
| US10576064B2 (en) | 2014-07-03 | 2020-03-03 | Boehringer Ingelheim International Gmbh | Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors |
| US20160052938A1 (en) | 2014-08-21 | 2016-02-25 | Boehringer Ingelheim International Gmbh | Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
| HRP20210960T1 (hr) | 2015-10-09 | 2021-09-03 | Boehringer Ingelheim International Gmbh | Spojevi i derivati spiro[3h-indol-3,2’-pirolidin]-2(1h)-ona kao inhibitori mdm2-p53 |
| KR102387316B1 (ko) | 2016-04-06 | 2022-04-15 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Mdm2 단백질 분해제 |
| PL3458101T3 (pl) | 2016-05-20 | 2021-05-31 | F. Hoffmann-La Roche Ag | Koniugaty PROTAC-przeciwciało i sposoby ich stosowania |
| BR112019021032A2 (pt) | 2017-04-05 | 2020-05-05 | Boehringer Ingelheim Int | terapia combinada anticâncer |
| US11339171B2 (en) * | 2017-12-29 | 2022-05-24 | Gan & Lee Pharmaceuticals | MDM2 inhibitors |
| 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 |
| US12480163B2 (en) * | 2018-07-18 | 2025-11-25 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification assessment, prevention, and treatment of Ewing sarcoma using TP53 dependency biomarkers and modulators |
| SE542672C2 (en) | 2018-09-14 | 2020-06-23 | Ausferritic Ab | Method for producing an ausferritic steel austempered during continuous cooling followed by annealing |
| US10590147B1 (en) | 2019-09-10 | 2020-03-17 | King Saud University | Spirooxindole-pyrrolothiazole heterocyclic hybrids |
| KR20230019462A (ko) | 2020-06-02 | 2023-02-08 | 베링거 인겔하임 인터내셔날 게엠베하 | 암 치료용 고리형 2-아미노-3-시아노 티오펜 및 유도체 |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| WO2023099592A1 (en) | 2021-12-01 | 2023-06-08 | Boehringer Ingelheim International Gmbh | 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 |
| TW202340208A (zh) | 2021-12-01 | 2023-10-16 | 德商百靈佳殷格翰國際股份有限公司 | 用於治療癌症之環狀2-胺基-3-氰基噻吩及衍生物 |
| CR20240233A (es) | 2021-12-01 | 2024-07-17 | Univ Vanderbilt | Tiofenos 2-amino-3-ciano anulados y derivados para el tratamiento del cáncer |
| US20250145608A1 (en) | 2021-12-01 | 2025-05-08 | Boehringer Ingelheim Int'l GmbH Corp. | Kras degrading compounds comprising annulated 2-amino-3-cyano thiophenes |
| US20250352535A1 (en) * | 2022-06-06 | 2025-11-20 | Kymera Therapeutics, Inc. | Mdm2 degraders and uses thereof |
| 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 |
| WO2024246099A1 (en) | 2023-05-30 | 2024-12-05 | Boehringer Ingelheim International Gmbh | Spirocyclic annulated 2-amino-3-cyano thiophenes and derivatives for the treatment of cancer |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2302650A1 (en) | 1997-09-08 | 1999-03-18 | William J. Ryan | Spiro¬pyrrolidine-2,3'-oxindole| compounds and methods of use |
| KR100944301B1 (ko) | 2005-02-22 | 2010-02-24 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Ｍｄｍ２의 소분자 억제제 및 이의 용도 |
| 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 |
| EP1858902A1 (en) | 2005-02-24 | 2007-11-28 | Pfizer Products Incorporated | Bicyclic heteroaromatic derivatives useful as anticancer agents |
| US20070213341A1 (en) | 2006-03-13 | 2007-09-13 | Li Chen | Spiroindolinone derivatives |
| EP1996591B1 (en) | 2006-03-13 | 2011-01-12 | F. Hoffmann-La Roche AG | Spiroindolinone derivatives |
| WO2008005268A1 (en) | 2006-06-30 | 2008-01-10 | Schering Corporation | Substituted piperidines that increase p53 activity and the uses thereof |
| AU2007297823B2 (en) | 2006-08-30 | 2012-04-19 | The Regents Of The University Of Michigan | New small molecule inhibitors of MDM2 and the uses thereof |
| CA2682483A1 (en) | 2007-03-29 | 2008-10-09 | Novartis Ag | 3-imidazolyl-indoles for the treatment of proliferative diseases |
| US7553833B2 (en) | 2007-05-17 | 2009-06-30 | Hoffmann-La Roche Inc. | 3,3-spiroindolinone derivatives |
| US7834179B2 (en) | 2007-05-23 | 2010-11-16 | Hoffmann-La Roche Inc. | Spiroindolinone derivatives |
| US8134001B2 (en) | 2007-12-14 | 2012-03-13 | Hoffmann-La Roche Inc. | Spiroindolinone derivatives |
| US7776875B2 (en) | 2007-12-19 | 2010-08-17 | Hoffman-La Roche Inc. | Spiroindolinone derivatives |
| TW201011009A (en) | 2008-09-15 | 2010-03-16 | Priaxon Ag | Novel pyrrolidin-2-ones |
| US20100190814A1 (en) | 2009-01-26 | 2010-07-29 | Li Chen | Spiroindolinone derivative prodrugs |
| US8076482B2 (en) | 2009-04-23 | 2011-12-13 | Hoffmann-La Roche Inc. | 3,3′-spiroindolinone derivatives |
| UA107814C2 (uk) | 2009-11-12 | 2015-02-25 | Дзе Ріджентс Оф Дзе Юніверсіті Оф Мічіган | Спірооксіндольні антагоністи мdм2 |
| US8088815B2 (en) | 2009-12-02 | 2012-01-03 | Hoffman-La Roche Inc. | Spiroindolinone pyrrolidines |
| US8288431B2 (en) | 2010-02-17 | 2012-10-16 | Hoffmann-La Roche Inc. | Substituted spiroindolinones |
| US8217044B2 (en) | 2010-04-28 | 2012-07-10 | Hoffmann-La Roche Inc. | Spiroindolinone pyrrolidines |
| 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 |
| TWI535723B (zh) | 2010-11-12 | 2016-06-01 | 密西根大學董事會 | 螺－吲哚酮ｍｄｍ２拮抗劑 |
| 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 |
| KR101779644B1 (ko) | 2011-03-10 | 2017-09-18 | 다이이찌 산쿄 가부시키가이샤 | 디스피로피롤리딘 유도체 |
| JP2014513699A (ja) | 2011-05-11 | 2014-06-05 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | スピロ−オキシインドールｍｄｍ２アンタゴニスト |
| 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 |
| EP3129380B1 (en) | 2014-04-11 | 2018-11-28 | Boehringer Ingelheim International Gmbh | Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one derivatives and their use as mdm2-p53 inhibitors |
| US10576064B2 (en) | 2014-07-03 | 2020-03-03 | Boehringer Ingelheim International Gmbh | Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one compounds and derivatives as MDM2-P53 inhibitors |
| NO2721710T3 (OSRAM) | 2014-08-21 | 2018-03-31 | ||
| US20160052938A1 (en) | 2014-08-21 | 2016-02-25 | Boehringer Ingelheim International Gmbh | Spiro[3h-indole-3,2'-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors |
| HRP20210960T1 (hr) | 2015-10-09 | 2021-09-03 | Boehringer Ingelheim International Gmbh | Spojevi i derivati spiro[3h-indol-3,2’-pirolidin]-2(1h)-ona kao inhibitori mdm2-p53 |
-
2015
- 2015-07-02 US US14/790,032 patent/US10576064B2/en active Active
- 2015-07-02 WO PCT/EP2015/065134 patent/WO2016001376A1/en not_active Ceased
- 2015-07-02 EP EP15732007.8A patent/EP3164401B1/en active Active
- 2015-07-02 JP JP2016575738A patent/JP6503386B2/ja active Active
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