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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Publication number
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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Mission Therapeutics Ltd
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Priority claimed from GBGB1700839.2A external-priority patent/GB201700839D0/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/14—Heterocyclic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/04—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/04—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/04—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—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
    • C07D417/14—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 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)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (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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CN201780018998.XA Active CN108884068B (zh) 2016-03-24 2017-03-23 作为dub抑制剂的1-氰基-吡咯烷衍生物

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Country Link
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
CA2976741C (en) 2015-03-30 2023-01-17 Mission Therapeutics Limited 1-cyano-pyrrolidine compounds as usp30 inhibitors
WO2017009650A1 (en) 2015-07-14 2017-01-19 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
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
US11014912B2 (en) 2016-09-27 2021-05-25 Mission Therapeutics Limited Cyanopyrrolidine derivatives with activity as inhibitors of 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
CN110831936B (zh) 2017-06-20 2023-03-28 特殊治疗有限公司 具有dub抑制剂活性的取代氰基吡咯烷
AU2018346597B2 (en) 2017-10-06 2023-07-13 Forma Therapeutics, Inc. Inhibiting Ubiquitin Specific Peptidase 30
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
US11572374B2 (en) 2018-08-14 2023-02-07 Amgen Inc. N-cyano-7-azanorbornane derivatives and uses thereof
JP7530889B2 (ja) * 2018-10-05 2024-08-08 フォーマ セラピューティクス，インコーポレイテッド ユビキチン特異的プロテアーゼ３０（ｕｓｐ３０）阻害剤として作用する縮合ピロリン
CN120698983A (zh) 2018-12-20 2025-09-26 C4医药公司 靶向蛋白降解
GB201905375D0 (en) 2019-04-16 2019-05-29 Mission Therapeutics Ltd Novel compounds
GB201905371D0 (en) 2019-04-16 2019-05-29 Mission Therapeutics Ltd Novel compounds
AU2020311940A1 (en) 2019-07-11 2022-02-03 ESCAPE Bio, Inc. Indazoles and azaindazoles as LRRK2 inhibitors
GB201912674D0 (en) * 2019-09-04 2019-10-16 Mission Therapeutics Ltd Novel compounds
JP2023520727A (ja) 2020-04-08 2023-05-18 ミッション セラピューティクス リミティド Ｕｓｐ３０阻害剤として活性を有するｎ－シアノピロリジン
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
US20230303547A1 (en) 2020-06-04 2023-09-28 Mission Therapeutics Limited N-cyanopyrrolidines with activity as usp30 inhibitors
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
JP2024544660A (ja) 2021-12-01 2024-12-03 ミッション セラピューティクス リミティド Ｕｓｐ３０阻害剤としての活性を有する置換ｎ－シアノピロリジン
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
EP1272467A4 (en) 2000-04-06 2003-05-07 Merck Frosst Canada Inc Cathepsin cysteine protease inhibitors
KR20140095513A (ko) 2011-11-01 2014-08-01 에프. 호프만-라 로슈 아게 이미다조피리다진 화합물
KR101668574B1 (ko) 2012-11-02 2016-10-24 화이자 인코포레이티드 브루톤 티로신 키나제 억제제
GB201309085D0 (en) 2013-05-20 2013-07-03 Redx Pharma Ltd Compounds
RS58361B1 (sr) 2013-07-31 2019-03-29 Merck Patent Gmbh Piridini, pirimidini i pirazini, kao inhibitori btk i njihova upotreba
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
PE20190710A1 (es) 2014-10-24 2019-05-17 Bristol Myers Squibb Co Compuestos de indol carboxamida utiles como inhibidores de cinasas
WO2016192074A1 (en) 2015-06-04 2016-12-08 Merck Sharp & Dohme Corp. Btk inhibitors
WO2017009650A1 (en) 2015-07-14 2017-01-19 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
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
WO2017172989A1 (en) 2016-03-30 2017-10-05 Thorpe Steven Brandon Sphingosine kinase inhibitor amidoxime prodrugs
WO2017198049A1 (zh) 2016-05-16 2017-11-23 浙江予川医药科技有限公司 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
KR102404759B1 (ko) 2016-05-16 2022-05-31 쑤저우 시노벤트 파마슈티칼즈 씨오., 엘티디. Ｂｔｋ 억제제로서의 5-아미노피라졸 카르복사미드 유도체 및 그것의 제조 방법 및 제약학적 조성물
US11014912B2 (en) 2016-09-27 2021-05-25 Mission Therapeutics Limited Cyanopyrrolidine derivatives with activity as inhibitors of 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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WO2017163078A8 (en) 2017-12-28
WO2017163078A1 (en) 2017-09-28
JP6959252B2 (ja) 2021-11-02
EP3433246B1 (en) 2022-05-04
US20220177451A1 (en) 2022-06-09
EP3433246A1 (en) 2019-01-30
US20200331888A1 (en) 2020-10-22
US11352339B2 (en) 2022-06-07
US11945797B2 (en) 2024-04-02
MA43753A (fr) 2018-11-28
CN108884068A (zh) 2018-11-23
JP2019513135A (ja) 2019-05-23

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