CN108884068B - 作为dub抑制剂的1-氰基-吡咯烷衍生物 - Google Patents

作为dub抑制剂的1-氰基-吡咯烷衍生物 Download PDF

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CN108884068B
CN108884068B CN201780018998.XA CN201780018998A CN108884068B CN 108884068 B CN108884068 B CN 108884068B CN 201780018998 A CN201780018998 A CN 201780018998A CN 108884068 B CN108884068 B CN 108884068B
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carbonitrile
pyrrolidine
oxadiazol
pyrazol
phenyl
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CN108884068A (zh
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A·琼斯
M·I·肯普
M·L·施托克利
M·D·伍德罗
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Mission Therapeutics Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/14Heterocyclic 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 three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Neurosurgery (AREA)
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  • Cardiology (AREA)
  • Transplantation (AREA)
  • Neurology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyrrole Compounds (AREA)
  • Pyridine Compounds (AREA)
CN201780018998.XA 2016-03-24 2017-03-23 作为dub抑制剂的1-氰基-吡咯烷衍生物 Active CN108884068B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GB1605059.3 2016-03-24
GBGB1605059.3A GB201605059D0 (en) 2016-03-24 2016-03-24 Novel compounds
GBGB1700839.2A GB201700839D0 (en) 2017-01-18 2017-01-18 Novel compounds
GB1700839.2 2017-01-18
PCT/GB2017/050830 WO2017163078A1 (en) 2016-03-24 2017-03-23 1-cyano-pyrrolidine derivatives as dbu inhibitors

Publications (2)

Publication Number Publication Date
CN108884068A CN108884068A (zh) 2018-11-23
CN108884068B true CN108884068B (zh) 2021-02-26

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US (2) US11352339B2 (https=)
EP (1) EP3433246B1 (https=)
JP (1) JP6959252B2 (https=)
CN (1) CN108884068B (https=)
MA (1) MA43753A (https=)
WO (1) WO2017163078A1 (https=)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX373656B (es) 2015-03-30 2020-04-02 Mission Therapeutics Ltd Compuestos de 1-ciano-pirrolidina como inhibidores de las enzimas desubiquitinantes, como la hidrolasa 30 de la c-terminal de la ubiquitina (usp30), y el uso de los mismos en el tratamiento de condiciones de disfunción mitocondrial y tratamiento de cancér.
US10669234B2 (en) 2015-07-14 2020-06-02 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
GB201522768D0 (en) 2015-12-23 2016-02-03 Mission Therapeutics Ltd Novel compounds
GB201602854D0 (en) 2016-02-18 2016-04-06 Mission Therapeutics Ltd Novel compounds
GB201603779D0 (en) 2016-03-04 2016-04-20 Mission Therapeutics Ltd Novel compounds
GB201604638D0 (en) 2016-03-18 2016-05-04 Mission Therapeutics Ltd Novel compounds
GB201604647D0 (en) 2016-03-18 2016-05-04 Mission Therapeutics Ltd Novel compounds
ES2850349T3 (es) 2016-09-27 2021-08-27 Mission Therapeutics Ltd Derivados de cianopirrolidina con actividad como inhibidores de USP30
GB201616511D0 (en) 2016-09-29 2016-11-16 Mission Therapeutics Limited Novel compounds
GB201616627D0 (en) 2016-09-30 2016-11-16 Mission Therapeutics Limited Novel compounds
TWI771327B (zh) 2016-10-05 2022-07-21 英商使命醫療公司 新穎化合物
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
BR112020003725A2 (pt) 2017-10-06 2020-11-03 Forma Therapeutics, Inc. inibição da peptidase 30 específica de ubiquitina
GB2571731A (en) * 2018-03-06 2019-09-11 Mission Therapeutics Ltd Novel compounds and uses
JP7449242B2 (ja) 2018-05-17 2024-03-13 フォーマ セラピューティクス,インコーポレイテッド ユビキチン特異的ペプチダーゼ30(usp30)阻害剤として有用な縮合二環化合物
JP7434285B2 (ja) * 2018-08-14 2024-02-20 アムジエン・インコーポレーテツド N-シアノ-7-アザノルボルナン誘導体及びその使用
LT3860989T (lt) * 2018-10-05 2023-06-12 Forma Therapeutics, Inc. Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai
CN120698983A (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
GB201905375D0 (en) 2019-04-16 2019-05-29 Mission Therapeutics Ltd Novel compounds
WO2021007477A1 (en) 2019-07-11 2021-01-14 E-Scape Bio, Inc. Indazoles and azaindazoles as lrrk2 inhibitors
GB201912674D0 (en) 2019-09-04 2019-10-16 Mission Therapeutics Ltd Novel compounds
WO2021204856A1 (en) * 2020-04-08 2021-10-14 Mission Therapeutics Limited N-cyanopyrrolidines with activity as usp30 inhibitors
IL298526A (en) 2020-05-28 2023-01-01 Mission Therapeutics Ltd N-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide derivatives and the corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction
BR112022019722A2 (pt) 2020-06-04 2022-12-20 Mission Therapeutics Ltd N-cianopirrolidinas com atividade como inibidores de usp30
DK4161929T3 (da) * 2020-06-08 2025-08-18 Mission Therapeutics Ltd 1-(5-(2-cyanopyridin-4-yl)oxazol-2-carbonyl)-4-methylhexahydropyrrolo[3,4-b]pyrrol-5(1h)-carbonitril som usp30-hæmmer til anvendelse i behandling af mitokondriedysfunktion, cancer og fibrose
GB202016800D0 (en) 2020-10-22 2020-12-09 Mission Therapeutics Ltd Novel compounds
US20250034122A1 (en) 2021-12-01 2025-01-30 Mission Therapeutics Limited Substituted n-cyanopyrrolidines with activity as usp30 inhibitors
CN114646700B (zh) * 2022-03-01 2023-10-20 浙江国邦药业有限公司 一种(s)-吡咯烷-2-甲腈盐酸盐的检测方法
GB202408928D0 (en) 2024-06-21 2024-08-07 Mission Therapeutics Ltd Novel compounds
GB202411060D0 (en) 2024-07-29 2024-09-11 Mission Therapeutics Ltd Novel compounds

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015061247A2 (en) * 2013-10-21 2015-04-30 Merck Patent Gmbh Heteroaryl compounds as btk inhibitors and uses thereof
WO2015158283A1 (en) * 2014-04-17 2015-10-22 Abbvie Inc. Heterocyclic kinase inhibitors
WO2015165279A1 (zh) * 2014-04-29 2015-11-05 浙江导明医药科技有限公司 多氟化合物作为布鲁顿酪氨酸激酶抑制剂
WO2016019237A2 (en) * 2014-07-31 2016-02-04 Pharmacyclics Llc Inhibitors of bruton's tyrosine kinase
CN107484415A (zh) * 2015-03-30 2017-12-15 特殊治疗有限公司 作为usp30抑制剂的1‑氰基吡咯烷化合物

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5665754A (en) 1993-09-20 1997-09-09 Glaxo Wellcome Inc. Substituted pyrrolidines
WO2001077073A1 (en) 2000-04-06 2001-10-18 Merck Frosst Canada & Co. Cathepsin cysteine protease inhibitors
RU2662443C2 (ru) 2011-11-01 2018-07-26 Ф. Хоффманн-Ля Рош Аг Имидазопиридазины
JP6178861B2 (ja) 2012-11-02 2017-08-09 ファイザー・インク ブルトン型チロシンキナーゼ阻害剤
GB201309085D0 (en) 2013-05-20 2013-07-03 Redx Pharma Ltd Compounds
CA2918242C (en) 2013-07-31 2022-06-21 Merck Patent Gmbh Pyridines, pyrimidines, and pyrazines, as btk inhibitors and uses thereof
GB201404987D0 (en) 2014-03-20 2014-05-07 Redx Pharma Ltd Compounds
GB201416754D0 (en) 2014-09-23 2014-11-05 Mission Therapeutics Ltd Novel compounds
EA034931B1 (ru) 2014-10-24 2020-04-08 Бристол-Майерс Сквибб Компани Индолкарбоксамидные соединения
WO2016192074A1 (en) 2015-06-04 2016-12-08 Merck Sharp & Dohme Corp. Btk inhibitors
US10669234B2 (en) 2015-07-14 2020-06-02 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
GB201522768D0 (en) 2015-12-23 2016-02-03 Mission Therapeutics Ltd Novel compounds
US10570118B2 (en) * 2016-01-13 2020-02-25 Boehringer Ingelheim International Gmbh Isoquinolones as BTK inhibitors
GB201602854D0 (en) 2016-02-18 2016-04-06 Mission Therapeutics Ltd Novel compounds
GB201603779D0 (en) 2016-03-04 2016-04-20 Mission Therapeutics Ltd Novel compounds
GB201604638D0 (en) 2016-03-18 2016-05-04 Mission Therapeutics Ltd Novel compounds
GB201604647D0 (en) 2016-03-18 2016-05-04 Mission Therapeutics Ltd Novel compounds
US11180489B2 (en) 2016-03-30 2021-11-23 U niversity of Virginia Patent Foundation Sphingosine kinase inhibitor amidoxime prodrugs
CN107383013B (zh) 2016-05-16 2020-03-31 苏州信诺维医药科技有限公司 作为btk抑制剂的吡唑并嘧啶衍生物及其制备方法和药物组合物
AU2017265219B2 (en) 2016-05-16 2021-02-04 Evopoint Biosciences Co., Ltd. 5-aminopyrazole carboxamide derivative as BTK inhibitor and preparation method and pharmaceutical composition thereof
ES2850349T3 (es) 2016-09-27 2021-08-27 Mission Therapeutics Ltd Derivados de cianopirrolidina con actividad como inhibidores de USP30
GB201616511D0 (en) 2016-09-29 2016-11-16 Mission Therapeutics Limited Novel compounds
GB201616627D0 (en) 2016-09-30 2016-11-16 Mission Therapeutics Limited Novel compounds
TWI771327B (zh) 2016-10-05 2022-07-21 英商使命醫療公司 新穎化合物

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015061247A2 (en) * 2013-10-21 2015-04-30 Merck Patent Gmbh Heteroaryl compounds as btk inhibitors and uses thereof
WO2015158283A1 (en) * 2014-04-17 2015-10-22 Abbvie Inc. Heterocyclic kinase inhibitors
WO2015165279A1 (zh) * 2014-04-29 2015-11-05 浙江导明医药科技有限公司 多氟化合物作为布鲁顿酪氨酸激酶抑制剂
WO2016019237A2 (en) * 2014-07-31 2016-02-04 Pharmacyclics Llc Inhibitors of bruton's tyrosine kinase
CN107484415A (zh) * 2015-03-30 2017-12-15 特殊治疗有限公司 作为usp30抑制剂的1‑氰基吡咯烷化合物

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MA43753A (fr) 2018-11-28
JP2019513135A (ja) 2019-05-23
US20200331888A1 (en) 2020-10-22
US11352339B2 (en) 2022-06-07
WO2017163078A1 (en) 2017-09-28
JP6959252B2 (ja) 2021-11-02
CN108884068A (zh) 2018-11-23
EP3433246A1 (en) 2019-01-30
US20220177451A1 (en) 2022-06-09
EP3433246B1 (en) 2022-05-04
US11945797B2 (en) 2024-04-02
WO2017163078A8 (en) 2017-12-28

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