CN114341133B - 具有usp30抑制剂活性的取代的氰基吡咯烷类 - Google Patents

具有usp30抑制剂活性的取代的氰基吡咯烷类 Download PDF

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CN114341133B
CN114341133B CN202080061743.3A CN202080061743A CN114341133B CN 114341133 B CN114341133 B CN 114341133B CN 202080061743 A CN202080061743 A CN 202080061743A CN 114341133 B CN114341133 B CN 114341133B
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CN114341133A (zh
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P·W·汤普森
C·A·卢克霍斯特
M·I·肯普
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Mission Therapeutics Ltd
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    • 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
    • C07D413/12Heterocyclic 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 linked by a chain containing hetero atoms as chain links
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245Oxadiazoles
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    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
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    • A61P25/08Antiepileptics; Anticonvulsants
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • AHUMAN NECESSITIES
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CN202080061743.3A 2019-09-04 2020-09-03 具有usp30抑制剂活性的取代的氰基吡咯烷类 Active CN114341133B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB1912674.7A GB201912674D0 (en) 2019-09-04 2019-09-04 Novel compounds
GB1912674.7 2019-09-04
PCT/EP2020/074540 WO2021043870A1 (en) 2019-09-04 2020-09-03 Substituted cyanopyrrolidines with activity as usp30 inhibitors

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CN114341133A CN114341133A (zh) 2022-04-12
CN114341133B true CN114341133B (zh) 2024-02-27

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US (1) US20220315572A1 (https=)
EP (1) EP4025573B9 (https=)
JP (1) JP2022546717A (https=)
KR (1) KR20220054867A (https=)
CN (1) CN114341133B (https=)
AU (1) AU2020340527A1 (https=)
BR (1) BR112022003527A2 (https=)
CA (1) CA3146040A1 (https=)
CO (1) CO2022003608A2 (https=)
GB (1) GB201912674D0 (https=)
IL (1) IL290929B2 (https=)
MX (1) MX2022002686A (https=)
WO (1) WO2021043870A1 (https=)
ZA (1) ZA202203775B (https=)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
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
KR20240132148A (ko) * 2023-02-24 2024-09-03 연세대학교 산학협력단 인덴 유도체를 유효성분으로 포함하는 섬유화의 예방 또는 치료용 조성물
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 (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016046530A1 (en) * 2014-09-23 2016-03-31 Mission Therapeutics Ltd Novel compounds
WO2016156816A1 (en) * 2015-03-30 2016-10-06 Mission Therapeutics Limited 1-cyano-pyrrolidine compounds as usp30 inhibitors
WO2017163078A1 (en) * 2016-03-24 2017-09-28 Mission Therapeutics Limited 1-cyano-pyrrolidine derivatives as dbu inhibitors
WO2019071073A1 (en) * 2017-10-06 2019-04-11 Forma Therapeutics, Inc. INHIBITION OF THE SPECIFIC PEPTIDASE OF UBIQUITIN

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9518953D0 (en) 1995-09-15 1995-11-15 Pfizer Ltd Pharmaceutical formulations
EP1272467A4 (en) 2000-04-06 2003-05-07 Merck Frosst Canada Inc Cathepsin cysteine protease inhibitors
PE20060777A1 (es) 2004-12-24 2006-10-06 Boehringer Ingelheim Int Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas
SG174050A1 (en) 2006-04-13 2011-09-29 Actelion Pharmaceuticals Ltd Endothelin receptor antagonists for early stage idiopathic pulmonary fibrosis
TWI433677B (zh) 2007-06-04 2014-04-11 Avila Therapeutics Inc 雜環化合物及其用途
US20090264431A1 (en) 2007-08-20 2009-10-22 Palovich Michael R Novel cathepsin c inhibitors and their use
WO2009129370A1 (en) 2008-04-18 2009-10-22 Glaxo Group Limited Cathepsin c inhibitors
WO2009129365A1 (en) 2008-04-18 2009-10-22 Glaxo Group Limited Cathepsin c inhibitors
WO2009129371A1 (en) 2008-04-18 2009-10-22 Glaxo Group Limited Cathepsin c inhibitors
US20120309820A1 (en) 2011-06-04 2012-12-06 Jb Therapeutics Inc. Methods of treating fibrotic diseases using tetrahydrocannabinol-11-oic acids
EP2565186A1 (en) 2011-09-02 2013-03-06 Hybrigenics S.A. Selective and reversible inhibitors of ubiquitin specific protease 7
RS58361B1 (sr) 2013-07-31 2019-03-29 Merck Patent Gmbh Piridini, pirimidini i pirazini, kao inhibitori btk i njihova upotreba
US9963444B2 (en) 2014-05-19 2018-05-08 Northeastern University N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
US20170095457A1 (en) 2014-05-27 2017-04-06 David Lonergan Compositions and methods of delivery of deubiquitinase inhibitors
WO2016019237A2 (en) 2014-07-31 2016-02-04 Pharmacyclics Llc Inhibitors of bruton's tyrosine kinase
WO2016040508A1 (en) * 2014-09-10 2016-03-17 Epizyme, Inc. Substituted pyrrolidine carboxamide compounds
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
US10968172B2 (en) 2017-05-15 2021-04-06 Mitobridge, Inc. USP30 inhibitors
GB201708652D0 (en) 2017-05-31 2017-07-12 Mission Therapeutics Ltd Novel compounds and uses
GB2563595B (en) 2017-06-19 2020-04-15 Edwards Ltd Twin-shaft pumps
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
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

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016046530A1 (en) * 2014-09-23 2016-03-31 Mission Therapeutics Ltd Novel compounds
WO2016156816A1 (en) * 2015-03-30 2016-10-06 Mission Therapeutics Limited 1-cyano-pyrrolidine compounds as usp30 inhibitors
WO2017163078A1 (en) * 2016-03-24 2017-09-28 Mission Therapeutics Limited 1-cyano-pyrrolidine derivatives as dbu inhibitors
WO2019071073A1 (en) * 2017-10-06 2019-04-11 Forma Therapeutics, Inc. INHIBITION OF THE SPECIFIC PEPTIDASE OF UBIQUITIN

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Novel highly selective inhibitors of ubiquitin specific protease 30 (USP30) accelerate mitophagy;Arthur F. Kluge et al.;《Bioorganic & Medicinal Chemistry Letters》;第28卷;第2655–2659页 *

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EP4025573B9 (en) 2024-11-20
CN114341133A (zh) 2022-04-12
JP2022546717A (ja) 2022-11-07
AU2020340527A1 (en) 2022-04-21
GB201912674D0 (en) 2019-10-16
MX2022002686A (es) 2022-04-07
BR112022003527A2 (pt) 2022-05-17
WO2021043870A1 (en) 2021-03-11
IL290929B1 (en) 2024-11-01
CO2022003608A2 (es) 2022-04-19
IL290929B2 (en) 2025-03-01
US20220315572A1 (en) 2022-10-06
IL290929A (en) 2022-04-01
KR20220054867A (ko) 2022-05-03
EP4025573A1 (en) 2022-07-13
CA3146040A1 (en) 2021-03-11
EP4025573B1 (en) 2024-07-24
ZA202203775B (en) 2024-01-31

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