CN108602823B - 作为去泛素化酶（dub）抑制剂的螺-缩合吡咯烷衍生物 - Google Patents

作为去泛素化酶（dub）抑制剂的螺-缩合吡咯烷衍生物 Download PDF

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CN108602823B
CN108602823B CN201780010388.5A CN201780010388A CN108602823B CN 108602823 B CN108602823 B CN 108602823B CN 201780010388 A CN201780010388 A CN 201780010388A CN 108602823 B CN108602823 B CN 108602823B
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oxo
pyrrolidine
dihydro
spiro
quinoline
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CN108602823A (zh
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M·I·肯普
M·L·斯托克利
M·D·伍德罗
A·琼斯
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Mission Therapeutics Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
    • 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
    • A61P35/00—Antineoplastic agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • 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
    • C07D471/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • C07D471/12—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 three hetero rings
    • C07D471/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/20—Spiro-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201780010388.5A 2016-03-04 2017-03-02 作为去泛素化酶（dub）抑制剂的螺-缩合吡咯烷衍生物 Active CN108602823B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1603779.8 2016-03-04
GBGB1603779.8A GB201603779D0 (en) 2016-03-04 2016-03-04 Novel compounds
PCT/GB2017/050565 WO2017149313A1 (en) 2016-03-04 2017-03-02 Spiro-condensed pyrrolidine derivatives as deubiquitylating enzymes (dub) inhibitors

Publications (2)

Publication Number Publication Date
CN108602823A CN108602823A (zh) 2018-09-28
CN108602823B true CN108602823B (zh) 2022-04-01

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CN201780010388.5A Active CN108602823B (zh) 2016-03-04 2017-03-02 作为去泛素化酶（dub）抑制剂的螺-缩合吡咯烷衍生物

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US (3) US10654853B2 (enExample)
EP (2) EP4067355A1 (enExample)
JP (2) JP6959247B2 (enExample)
KR (1) KR102384139B1 (enExample)
CN (1) CN108602823B (enExample)
AU (1) AU2017225371B2 (enExample)
BR (1) BR112018017086B1 (enExample)
CA (1) CA3016370C (enExample)
CO (1) CO2018009275A2 (enExample)
ES (1) ES2919549T3 (enExample)
GB (1) GB201603779D0 (enExample)
IL (1) IL261552B (enExample)
MA (1) MA43701A (enExample)
MX (1) MX382562B (enExample)
MY (1) MY196836A (enExample)
RU (1) RU2730552C2 (enExample)
SG (1) SG11201807301SA (enExample)
WO (1) WO2017149313A1 (enExample)
ZA (1) ZA201803910B (enExample)

Families Citing this family (31)

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EP3277677B9 (en) 2015-03-30 2021-07-14 Mission Therapeutics Limited 1-cyano-pyrrolidine compounds as usp30 inhibitors
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
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
WO2017163078A1 (en) 2016-03-24 2017-09-28 Mission Therapeutics Limited 1-cyano-pyrrolidine derivatives as dbu inhibitors
EP3519385B1 (en) 2016-09-27 2020-11-18 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
US11059809B2 (en) 2017-06-20 2021-07-13 Mission Therapeutics Limited Substituted cyanopyrrolidines with activity as DUB inhibitors
US11247987B2 (en) 2017-10-06 2022-02-15 Forma Therapeutics, Inc. Inhibiting ubiquitin specific peptidase 30
IL278291B2 (en) 2018-05-17 2023-10-01 Forma Therapeutics Inc Fused bicyclic compounds useful as ubiquitin-specific peptidase 30 inhibitors
US11572374B2 (en) 2018-08-14 2023-02-07 Amgen Inc. N-cyano-7-azanorbornane derivatives and uses thereof
LT3860989T (lt) 2018-10-05 2023-06-12 Forma Therapeutics, Inc. Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai
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
GB201912674D0 (en) 2019-09-04 2019-10-16 Mission Therapeutics Ltd Novel compounds
CN115461340A (zh) 2020-04-08 2022-12-09 特殊治疗有限公司 具有作为usp30抑制剂活性的n-氰基吡咯烷类化合物
WO2021239863A1 (en) 2020-05-28 2021-12-02 Mission Therapeutics Limited 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
CN115698001A (zh) 2020-06-04 2023-02-03 特殊治疗有限公司 具有作为usp30抑制剂活性的n-氰基吡咯烷类化合物
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
GB202016800D0 (en) 2020-10-22 2020-12-09 Mission Therapeutics Ltd Novel compounds
CN116143782B (zh) * 2021-11-22 2024-04-12 西南大学 一类螺[吡咯烷-2,3'-喹啉]-2'-酮类衍生物的设计合成与应用
US20250034122A1 (en) 2021-12-01 2025-01-30 Mission Therapeutics Limited Substituted n-cyanopyrrolidines with activity as usp30 inhibitors
WO2024151847A1 (en) * 2023-01-13 2024-07-18 The University Of North Carolina At Chapel Hill Identification of otud7b inhibitor 7bi and its application in reducing growth of nsclc and leukemia cells

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WO2008036168A2 (en) * 2006-08-30 2008-03-27 The Regents Of The University Of Michigan New small molecule inhibitors of mdm2 and the uses thereof
WO2009026197A1 (en) * 2007-08-20 2009-02-26 Glaxo Group Limited Novel cathepsin c inhibitors and their use
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GB201616627D0 (en) 2016-09-30 2016-11-16 Mission Therapeutics Limited Novel compounds
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WO2008036168A2 (en) * 2006-08-30 2008-03-27 The Regents Of The University Of Michigan New small molecule inhibitors of mdm2 and the uses thereof
WO2009026197A1 (en) * 2007-08-20 2009-02-26 Glaxo Group Limited Novel cathepsin c inhibitors and their use
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EP4067355A1 (en) 2022-10-05
KR20180119644A (ko) 2018-11-02
AU2017225371B2 (en) 2020-07-02
SG11201807301SA (en) 2018-09-27
RU2018133279A3 (enExample) 2020-04-06
AU2017225371A1 (en) 2018-10-11
ZA201803910B (en) 2020-01-29
US11236092B2 (en) 2022-02-01
EP3423454A1 (en) 2019-01-09
NZ746531A (en) 2022-03-25
BR112018017086A2 (pt) 2019-01-02
EP3423454B1 (en) 2022-05-25
WO2017149313A1 (en) 2017-09-08
US20220106315A1 (en) 2022-04-07
ES2919549T3 (es) 2022-07-27
RU2730552C2 (ru) 2020-08-24
CA3016370C (en) 2023-08-01
IL261552B (en) 2021-03-25
CN108602823A (zh) 2018-09-28
MX382562B (es) 2025-03-13
CA3016370A1 (en) 2017-09-08
US20190048008A1 (en) 2019-02-14
JP6959247B2 (ja) 2021-11-02
BR112018017086B1 (pt) 2024-02-20
HK1258589A1 (zh) 2019-11-15
CO2018009275A2 (es) 2018-10-10
MY196836A (en) 2023-05-03
GB201603779D0 (en) 2016-04-20
RU2018133279A (ru) 2020-04-06
KR102384139B1 (ko) 2022-04-07
JP2021193144A (ja) 2021-12-23
JP7280928B2 (ja) 2023-05-24
MA43701A (fr) 2018-11-28
US20200247803A1 (en) 2020-08-06
IL261552A (en) 2018-10-31
JP2019507177A (ja) 2019-03-14
US10654853B2 (en) 2020-05-19

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