CA3016370C - Spiro-condensed pyrrolidine derivatives as deubiquitylating enzymes (dub) inhibitors - Google Patents

Spiro-condensed pyrrolidine derivatives as deubiquitylating enzymes (dub) inhibitors Download PDF

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Publication number
CA3016370C
CA3016370C CA3016370A CA3016370A CA3016370C CA 3016370 C CA3016370 C CA 3016370C CA 3016370 A CA3016370 A CA 3016370A CA 3016370 A CA3016370 A CA 3016370A CA 3016370 C CA3016370 C CA 3016370C
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Prior art keywords
oxo
pyrrolidine
spiro
carbonitrile
dihydro
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CA3016370A
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English (en)
French (fr)
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CA3016370A1 (en
Inventor
Mark Ian Kemp
Martin Lee Stockley
Michael David Woodrow
Alison Jones
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Mission Therapeutics Ltd
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Mission Therapeutics Ltd
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Publication of CA3016370A1 publication Critical patent/CA3016370A1/en
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/10Spiro-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/537Heterocyclic 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
    • 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
    • A61P35/00Antineoplastic agents
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/12Heterocyclic 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
    • C07D471/20Spiro-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/10Spiro-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12Heterocyclic 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
    • C07D498/20Spiro-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)
CA3016370A 2016-03-04 2017-03-02 Spiro-condensed pyrrolidine derivatives as deubiquitylating enzymes (dub) inhibitors Active CA3016370C (en)

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
CA3016370A1 CA3016370A1 (en) 2017-09-08
CA3016370C true CA3016370C (en) 2023-08-01

Family

ID=55859019

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3016370A Active CA3016370C (en) 2016-03-04 2017-03-02 Spiro-condensed pyrrolidine derivatives as deubiquitylating enzymes (dub) inhibitors

Country Status (19)

Country Link
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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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AU2001256981A1 (en) 2000-04-06 2001-10-23 Axys Pharmaceuticals, Inc. Cathepsin cysteine protease inhibitors
SG176463A1 (en) 2005-02-22 2011-12-29 Univ Michigan Small molecule inhibitors of mdm2 and uses thereof
CA2661354C (en) * 2006-08-30 2012-12-18 The Regents Of The University Of Michigan New small molecule inhibitors of mdm2 and the uses thereof
WO2008144507A2 (en) 2007-05-16 2008-11-27 President And Fellows Of Harvard College Spirooxindole inhibitors of aurora kinase
UY31299A1 (es) * 2007-08-20 2009-03-31 Nuevos inhibidores de catepsina y su uso
US8088815B2 (en) * 2009-12-02 2012-01-03 Hoffman-La Roche Inc. Spiroindolinone pyrrolidines
GB0922589D0 (en) 2009-12-23 2010-02-10 Almac Discovery Ltd Pharmaceutical compounds
WO2012121361A1 (ja) * 2011-03-10 2012-09-13 第一三共株式会社 ジスピロピロリジン誘導体
EP2752191A1 (en) 2013-01-07 2014-07-09 Sanofi Compositions and methods using hdm2 antagonist and mek inhibitor
GB201416754D0 (en) * 2014-09-23 2014-11-05 Mission Therapeutics Ltd Novel compounds
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
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
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

Also Published As

Publication number Publication date
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
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
CN108602823B (zh) 2022-04-01
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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