TWI771327B - 新穎化合物 - Google Patents
新穎化合物 Download PDFInfo
- Publication number
- TWI771327B TWI771327B TW106134051A TW106134051A TWI771327B TW I771327 B TWI771327 B TW I771327B TW 106134051 A TW106134051 A TW 106134051A TW 106134051 A TW106134051 A TW 106134051A TW I771327 B TWI771327 B TW I771327B
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- TW
- Taiwan
- Prior art keywords
- cyano
- carboxamide
- optionally substituted
- alkyl
- ring
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 253
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 22
- 201000011510 cancer Diseases 0.000 claims abstract description 16
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- 108090000790 Enzymes Proteins 0.000 claims abstract description 3
- -1 nitro, hydroxyl Chemical group 0.000 claims description 254
- 239000001257 hydrogen Substances 0.000 claims description 171
- 229910052739 hydrogen Inorganic materials 0.000 claims description 171
- 125000003118 aryl group Chemical group 0.000 claims description 124
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 113
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 105
- 229910052736 halogen Inorganic materials 0.000 claims description 103
- 125000000623 heterocyclic group Chemical group 0.000 claims description 100
- 125000000217 alkyl group Chemical group 0.000 claims description 96
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 96
- 125000003545 alkoxy group Chemical group 0.000 claims description 88
- 125000001424 substituent group Chemical group 0.000 claims description 84
- 150000002367 halogens Chemical class 0.000 claims description 83
- 125000002950 monocyclic group Chemical group 0.000 claims description 81
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 79
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 78
- 229910052731 fluorine Inorganic materials 0.000 claims description 74
- 239000011737 fluorine Substances 0.000 claims description 73
- 229910052757 nitrogen Inorganic materials 0.000 claims description 73
- 125000002619 bicyclic group Chemical group 0.000 claims description 62
- 150000002431 hydrogen Chemical class 0.000 claims description 60
- 229910052760 oxygen Inorganic materials 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 60
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 41
- 239000001301 oxygen Chemical group 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 125000005842 heteroatom Chemical group 0.000 claims description 37
- 229910052717 sulfur Inorganic materials 0.000 claims description 37
- 239000000460 chlorine Substances 0.000 claims description 34
- 229910052801 chlorine Inorganic materials 0.000 claims description 33
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 32
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 30
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 28
- 229910052702 rhenium Inorganic materials 0.000 claims description 28
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 27
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- 239000011593 sulfur Chemical group 0.000 claims description 25
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 21
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 125000000335 thiazolyl group Chemical group 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 9
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
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- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- LSNOAQQZECGQNS-UHFFFAOYSA-N morpholine-2-carboxamide Chemical compound NC(=O)C1CNCCO1 LSNOAQQZECGQNS-UHFFFAOYSA-N 0.000 claims description 6
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- 102000018653 Long-Chain Acyl-CoA Dehydrogenase Human genes 0.000 claims description 4
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- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- XIMBESZRBTVIOD-UHFFFAOYSA-N piperidine-2-carboxamide Chemical compound NC(=O)C1CCCCN1 XIMBESZRBTVIOD-UHFFFAOYSA-N 0.000 claims description 4
- 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 claims description 4
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- PYXOJYSQURVYMA-ARLHGKGLSA-N (2R)-4-cyano-N-[1-(4-cyanopyridin-2-yl)pyrrolidin-3-yl]morpholine-2-carboxamide Chemical compound C(#N)N1C[C@@H](OCC1)C(=O)NC1CN(CC1)C1=NC=CC(=C1)C#N PYXOJYSQURVYMA-ARLHGKGLSA-N 0.000 claims description 3
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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| MA48994A (fr) | 2017-03-30 | 2020-02-05 | Hoffmann La Roche | Isoquinoléines utilisées en tant qu'inhibiteurs de hpk1 |
| GB201708652D0 (en) | 2017-05-31 | 2017-07-12 | Mission Therapeutics Ltd | Novel compounds and uses |
| JP7208931B2 (ja) | 2017-06-20 | 2023-01-19 | ミッション セラピューティクス リミティド | Dub阻害剤としての活性をもつ置換シアノピロリジン類 |
| US11247987B2 (en) | 2017-10-06 | 2022-02-15 | Forma Therapeutics, Inc. | Inhibiting ubiquitin specific peptidase 30 |
| ES2988920T3 (es) * | 2018-05-17 | 2024-11-22 | Forma Therapeutics Inc | Compuestos bicíclicos fusionados útiles como inhibidores de la peptidasa 30 específica de ubiquitina |
| JP7386841B2 (ja) | 2018-07-24 | 2023-11-27 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | イソキノリン化合物及びその使用 |
| TW202024053A (zh) | 2018-10-02 | 2020-07-01 | 美商建南德克公司 | 異喹啉化合物及其用途 |
| US11612606B2 (en) | 2018-10-03 | 2023-03-28 | Genentech, Inc. | 8-aminoisoquinoline compounds and uses thereof |
| MX2021002981A (es) | 2018-10-05 | 2021-05-14 | Forma Therapeutics Inc | Pirrolinas fusionadas que actuan como inhibidores de la proteasa 30 especifica de la ubiquitina (usp30). |
| CN120698985A (zh) | 2018-12-20 | 2025-09-26 | C4医药公司 | 靶向蛋白降解 |
| GB201905371D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
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| GB201912674D0 (en) | 2019-09-04 | 2019-10-16 | Mission Therapeutics Ltd | Novel compounds |
| BR112022020058A2 (pt) | 2020-04-08 | 2022-11-22 | Mission Therapeutics Ltd | N-cianopirrolidinas com atividade como inibidores de usp30 |
| CN115667252A (zh) | 2020-05-28 | 2023-01-31 | 特殊治疗有限公司 | 用于治疗线粒体功能障碍的作为usp30抑制剂的n-(1-氰基-吡咯烷-3-基)-5-(3-(三氟甲基)苯基)噁唑-2-甲酰胺衍生物和对应噁二唑衍生物 |
| BR112022019722A2 (pt) | 2020-06-04 | 2022-12-20 | Mission Therapeutics Ltd | N-cianopirrolidinas com atividade como inibidores de usp30 |
| FI4161929T3 (fi) | 2020-06-08 | 2025-07-30 | Mission Therapeutics Ltd | 1-(5-(2-syaanipyridin-4-yyli)oksatsoli-2-karbonyyli)-4-metyyliheksahydropyrrolo[3,4-b]pyrroli-5(1h)-karbonitriili usp30-inhibiittorina käytettäväksi mitokondrioiden toimintahäiriön, syövän ja fibroosin hoitamisessa |
| CN112029738B (zh) * | 2020-08-18 | 2022-04-29 | 浙江省人民医院 | 人parkin蛋白乙酰化及其在药物制备中的应用 |
| GB202016800D0 (en) | 2020-10-22 | 2020-12-09 | Mission Therapeutics Ltd | Novel compounds |
| EP4441044A1 (en) | 2021-12-01 | 2024-10-09 | Mission Therapeutics Limited | Substituted n-cyanopyrrolidines with activity as usp30 inhibitors |
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| EP0034471A1 (en) * | 1980-02-19 | 1981-08-26 | Orion-Yhtymä Oy | Piperidinoquinazolines and a process for the preparation thereof |
| WO2016046530A1 (en) * | 2014-09-23 | 2016-03-31 | Mission Therapeutics Ltd | Novel compounds |
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| US5861395A (en) * | 1996-09-13 | 1999-01-19 | Schering Corporation | Compounds useful for inhibition of farnesyl proteins transferase |
| US6635661B2 (en) | 2000-05-25 | 2003-10-21 | Sepracor Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| AU2001256981A1 (en) | 2000-04-06 | 2001-10-23 | Axys Pharmaceuticals, Inc. | Cathepsin cysteine protease inhibitors |
| WO2003082290A1 (de) * | 2002-03-30 | 2003-10-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 4- ( n-phenylamino ) -chinazoline/chinoline als tyrosinkinaseinhibitoren |
| WO2006110884A2 (en) | 2005-04-11 | 2006-10-19 | Neurocrine Biosciences, Inc. | 2, 6-di (hetero) aryl -4-amido-pyrimidines as adenosine receptor antagonists |
| WO2010120854A1 (en) * | 2009-04-15 | 2010-10-21 | Glaxosmithkline Llc | Chemical compounds |
| HK1211293A1 (en) * | 2012-11-02 | 2016-05-20 | 辉瑞公司 | Bruton's tyrosine kinase inhibitors |
| WO2015017502A1 (en) * | 2013-07-31 | 2015-02-05 | Merck Patent Gmbh | Pyridines, pyrimidines, and pyrazines, as btk inhibitors and uses thereof |
| CN107484415B (zh) | 2015-03-30 | 2021-01-29 | 特殊治疗有限公司 | 作为usp30抑制剂的1-氰基吡咯烷化合物 |
| EP3322702B1 (en) | 2015-07-14 | 2019-11-20 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
| GB201521109D0 (en) | 2015-11-30 | 2016-01-13 | Mission Therapeutics Ltd | Novel compounds |
| GB201522267D0 (en) | 2015-12-17 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
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| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| WO2017163078A1 (en) | 2016-03-24 | 2017-09-28 | Mission Therapeutics Limited | 1-cyano-pyrrolidine derivatives as dbu inhibitors |
| CN109790112B (zh) | 2016-09-27 | 2022-08-26 | 特殊治疗有限公司 | 具有作为usp30抑制剂活性的氰基吡咯烷衍生物 |
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| GB201708652D0 (en) | 2017-05-31 | 2017-07-12 | Mission Therapeutics Ltd | Novel compounds and uses |
| JP7208931B2 (ja) | 2017-06-20 | 2023-01-19 | ミッション セラピューティクス リミティド | Dub阻害剤としての活性をもつ置換シアノピロリジン類 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0034471A1 (en) * | 1980-02-19 | 1981-08-26 | Orion-Yhtymä Oy | Piperidinoquinazolines and a process for the preparation thereof |
| WO2016046530A1 (en) * | 2014-09-23 | 2016-03-31 | Mission Therapeutics Ltd | Novel compounds |
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| US11370784B2 (en) | 2022-06-28 |
| JP2019533659A (ja) | 2019-11-21 |
| CN109803963A (zh) | 2019-05-24 |
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