KR102384139B1 - 탈유비퀴틴화 효소(dub) 억제제로서 스피로-축합된 피롤리딘 유도체 - Google Patents

탈유비퀴틴화 효소(dub) 억제제로서 스피로-축합된 피롤리딘 유도체 Download PDF

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KR102384139B1
KR102384139B1 KR1020187028269A KR20187028269A KR102384139B1 KR 102384139 B1 KR102384139 B1 KR 102384139B1 KR 1020187028269 A KR1020187028269 A KR 1020187028269A KR 20187028269 A KR20187028269 A KR 20187028269A KR 102384139 B1 KR102384139 B1 KR 102384139B1
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oxo
pyrrolidine
carbonitrile
dihydro
spiro
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KR20180119644A (ko
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마크 이안 켐프
마틴 리 스톡리
마이클 데이비드 우드로우
앨리슨 존스
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미션 테라퓨틱스 엘티디
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    • 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
    • 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
    • C07D471/12—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)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (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)
KR1020187028269A 2016-03-04 2017-03-02 탈유비퀴틴화 효소(dub) 억제제로서 스피로-축합된 피롤리딘 유도체 Active KR102384139B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB1603779.8A GB201603779D0 (en) 2016-03-04 2016-03-04 Novel compounds
GB1603779.8 2016-03-04
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
KR20180119644A KR20180119644A (ko) 2018-11-02
KR102384139B1 true KR102384139B1 (ko) 2022-04-07

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

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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
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
JP6959252B2 (ja) 2016-03-24 2021-11-02 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１−シアノピロリジン誘導体
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
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
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
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
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
MX2024007932A (es) * 2021-12-23 2024-09-18 Univ Leuven Kath Spiros y analogos relacionados para inhibir yap/taz-tead.
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
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

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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
US20120264738A1 (en) 2011-03-10 2012-10-18 Yuuichi Sugimoto Dispiropyrrolidine derivatives
WO2016046530A1 (en) 2014-09-23 2016-03-31 Mission Therapeutics Ltd Novel compounds

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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
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
JP6959252B2 (ja) 2016-03-24 2021-11-02 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１−シアノピロリジン誘導体
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

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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
US20120264738A1 (en) 2011-03-10 2012-10-18 Yuuichi Sugimoto Dispiropyrrolidine derivatives
WO2016046530A1 (en) 2014-09-23 2016-03-31 Mission Therapeutics Ltd Novel compounds

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JP2021193144A (ja) 2021-12-23
SG11201807301SA (en) 2018-09-27
US11236092B2 (en) 2022-02-01
KR20180119644A (ko) 2018-11-02
EP3423454B1 (en) 2022-05-25
IL261552A (en) 2018-10-31
CO2018009275A2 (es) 2018-10-10
US20200247803A1 (en) 2020-08-06
MY196836A (en) 2023-05-03
NZ746531A (en) 2022-03-25
AU2017225371A1 (en) 2018-10-11
WO2017149313A1 (en) 2017-09-08
RU2730552C2 (ru) 2020-08-24
US10654853B2 (en) 2020-05-19
JP6959247B2 (ja) 2021-11-02
MX382562B (es) 2025-03-13
ZA201803910B (en) 2020-01-29
MA43701A (fr) 2018-11-28
BR112018017086B1 (pt) 2024-02-20
ES2919549T3 (es) 2022-07-27
US20190048008A1 (en) 2019-02-14
RU2018133279A3 (https=) 2020-04-06
HK1258589A1 (zh) 2019-11-15
BR112018017086A2 (pt) 2019-01-02
CN108602823B (zh) 2022-04-01
EP4067355A1 (en) 2022-10-05
IL261552B (en) 2021-03-25
RU2018133279A (ru) 2020-04-06
CA3016370C (en) 2023-08-01
CA3016370A1 (en) 2017-09-08
EP3423454A1 (en) 2019-01-09
GB201603779D0 (en) 2016-04-20
AU2017225371B2 (en) 2020-07-02
US20220106315A1 (en) 2022-04-07
CN108602823A (zh) 2018-09-28
JP2019507177A (ja) 2019-03-14
JP7280928B2 (ja) 2023-05-24

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