JP6959247B2 - 脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体 - Google Patents

脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体 Download PDF

Info

Publication number
JP6959247B2
JP6959247B2 JP2018546518A JP2018546518A JP6959247B2 JP 6959247 B2 JP6959247 B2 JP 6959247B2 JP 2018546518 A JP2018546518 A JP 2018546518A JP 2018546518 A JP2018546518 A JP 2018546518A JP 6959247 B2 JP6959247 B2 JP 6959247B2
Authority
JP
Japan
Prior art keywords
oxo
carbonitrile
pyrrolidine
dihydro
spiro
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2018546518A
Other languages
English (en)
Japanese (ja)
Other versions
JP2019507177A (ja
JP2019507177A5 (enExample
Inventor
イアン ケンプ マーク
リー ストックリー マーティン
デイビッド ウッドロー マイケル
ジョーンズ アリソン
Original Assignee
ミッション セラピューティクス リミティド
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ミッション セラピューティクス リミティド filed Critical ミッション セラピューティクス リミティド
Publication of JP2019507177A publication Critical patent/JP2019507177A/ja
Publication of JP2019507177A5 publication Critical patent/JP2019507177A5/ja
Priority to JP2021158986A priority Critical patent/JP7280928B2/ja
Application granted granted Critical
Publication of JP6959247B2 publication Critical patent/JP6959247B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
JP2018546518A 2016-03-04 2017-03-02 脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体 Active JP6959247B2 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2021158986A JP7280928B2 (ja) 2016-03-04 2021-09-29 脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体

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

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2021158986A Division JP7280928B2 (ja) 2016-03-04 2021-09-29 脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体

Publications (3)

Publication Number Publication Date
JP2019507177A JP2019507177A (ja) 2019-03-14
JP2019507177A5 JP2019507177A5 (enExample) 2020-02-27
JP6959247B2 true JP6959247B2 (ja) 2021-11-02

Family

ID=55859019

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2018546518A Active JP6959247B2 (ja) 2016-03-04 2017-03-02 脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体
JP2021158986A Active JP7280928B2 (ja) 2016-03-04 2021-09-29 脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2021158986A Active JP7280928B2 (ja) 2016-03-04 2021-09-29 脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体

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
DK3277677T3 (da) 2015-03-30 2021-05-25 Mission Therapeutics Ltd 1-cyano-pyrrolidinforbindelser som usp30-hæmmere
JP6802251B2 (ja) 2015-07-14 2020-12-16 ミッション セラピューティクス リミティド 癌の処置のためのｄｕｂ阻害剤としてのシアノピロリジン
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
CN109790112B (zh) 2016-09-27 2022-08-26 特殊治疗有限公司 具有作为usp30抑制剂活性的氰基吡咯烷衍生物
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
EP3642196B1 (en) 2017-06-20 2022-08-17 Mission Therapeutics Limited Substituted cyanopyrrolidines with activity as dub inhibitors
EP3692028B1 (en) 2017-10-06 2023-04-26 Forma Therapeutics, Inc. Inhibiting ubiquitin specific peptidase 30
CN112513036B (zh) 2018-05-17 2024-05-24 福马治疗有限公司 用作泛素特异性肽酶30抑制剂的稠合双环化合物
EP3837262A1 (en) 2018-08-14 2021-06-23 Amgen Inc. N-cyano-7-azanorbornane derivatives and uses thereof
FI3860989T3 (fi) 2018-10-05 2023-05-25 Forma Therapeutics Inc Ubikitiinispesifisen proteaasi 30:n (usp30) inhiboiminen
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
KR20230006487A (ko) 2020-04-08 2023-01-10 미션 테라퓨틱스 엘티디 Usp30 억제제로서의 활성을 갖는 n-시아노피롤리딘
CN115667252A (zh) 2020-05-28 2023-01-31 特殊治疗有限公司 用于治疗线粒体功能障碍的作为usp30抑制剂的n-(1-氰基-吡咯烷-3-基)-5-(3-(三氟甲基)苯基)噁唑-2-甲酰胺衍生物和对应噁二唑衍生物
WO2021245186A1 (en) 2020-06-04 2021-12-09 Mission Therapeutics Limited N-cyanopyrrolidines with activity as usp30 inhibitors
KR20230022215A (ko) 2020-06-08 2023-02-14 미션 테라퓨틱스 엘티디 미토콘드리아 기능장애, 암 및 섬유증의 치료에 사용하기 위한 USP30 억제제로서 1-(5-(2-시아노피리딘-4-일)옥사졸-2-카보닐)-4-메틸헥사하이드로피롤로[3,4-b]피롤-5(1H)-카보니트릴
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

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1272467A4 (en) 2000-04-06 2003-05-07 Merck Frosst Canada Inc Cathepsin cysteine protease inhibitors
US7759383B2 (en) 2005-02-22 2010-07-20 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 and the uses thereof
ZA200901224B (en) * 2006-08-30 2010-05-26 Univ Michigan New small molecule inhibitors of MDM2 the uses thereof
WO2008144507A2 (en) 2007-05-16 2008-11-27 President And Fellows Of Harvard College Spirooxindole inhibitors of aurora kinase
WO2009026197A1 (en) * 2007-08-20 2009-02-26 Glaxo Group Limited Novel cathepsin c inhibitors and their use
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
MY172862A (en) * 2011-03-10 2019-12-13 Daiichi Sankyo Co Ltd Dispiropyrrolidine derivatives
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
DK3277677T3 (da) 2015-03-30 2021-05-25 Mission Therapeutics Ltd 1-cyano-pyrrolidinforbindelser som usp30-hæmmere
JP6802251B2 (ja) 2015-07-14 2020-12-16 ミッション セラピューティクス リミティド 癌の処置のためのｄｕｂ阻害剤としてのシアノピロリジン
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
CN109790112B (zh) 2016-09-27 2022-08-26 特殊治疗有限公司 具有作为usp30抑制剂活性的氰基吡咯烷衍生物
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
MY196836A (en) 2023-05-03
BR112018017086B1 (pt) 2024-02-20
MX382562B (es) 2025-03-13
US10654853B2 (en) 2020-05-19
US20200247803A1 (en) 2020-08-06
CN108602823A (zh) 2018-09-28
ZA201803910B (en) 2020-01-29
EP3423454A1 (en) 2019-01-09
KR102384139B1 (ko) 2022-04-07
WO2017149313A1 (en) 2017-09-08
JP7280928B2 (ja) 2023-05-24
SG11201807301SA (en) 2018-09-27
IL261552B (en) 2021-03-25
CA3016370C (en) 2023-08-01
NZ746531A (en) 2022-03-25
US20220106315A1 (en) 2022-04-07
JP2021193144A (ja) 2021-12-23
AU2017225371B2 (en) 2020-07-02
CN108602823B (zh) 2022-04-01
BR112018017086A2 (pt) 2019-01-02
ES2919549T3 (es) 2022-07-27
EP3423454B1 (en) 2022-05-25
EP4067355A1 (en) 2022-10-05
RU2730552C2 (ru) 2020-08-24
AU2017225371A1 (en) 2018-10-11
HK1258589A1 (zh) 2019-11-15
KR20180119644A (ko) 2018-11-02
CO2018009275A2 (es) 2018-10-10
CA3016370A1 (en) 2017-09-08
US20190048008A1 (en) 2019-02-14
JP2019507177A (ja) 2019-03-14
RU2018133279A (ru) 2020-04-06
MA43701A (fr) 2018-11-28
RU2018133279A3 (enExample) 2020-04-06
GB201603779D0 (en) 2016-04-20
US11236092B2 (en) 2022-02-01
IL261552A (en) 2018-10-31

Similar Documents

Publication Publication Date Title
JP6959247B2 (ja) 脱ユビキチン化酵素（ｄｕｂ）阻害剤としてのスピロ縮合ピロリジン誘導体
JP6916197B2 (ja) 新規化合物
JP7044769B2 (ja) Ｕｓｐ３０の阻害剤としての活性を有するシアノ置換複素環
JP7084918B2 (ja) Ｕｓｐ３０の阻害剤としての活性を有するシアノピロリジン誘導体
JP6898327B2 (ja) 新規化合物
JP6802251B2 (ja) 癌の処置のためのｄｕｂ阻害剤としてのシアノピロリジン
JP6959250B2 (ja) 癌治療用の２−シアノイソインドリン誘導体
JP6810148B2 (ja) Ｄｕｂの阻害剤としてのシアノピロリジン誘導体
JP6823064B2 (ja) Ｕｓｐ３０の阻害剤としての１−シアノピロリジン誘導体
JP2020143124A (ja) Ｕｓｐ３０阻害剤としての１−シアノ−ピロリジン化合物
US20120202828A1 (en) Fused aminodihydropyrimidone derivatives
HK1258589B (en) Spiro-condensed pyrrolidine derivatives as deubiquitylating enzymes (dub) inhibitors
NZ746531B2 (en) Spiro-condensed pyrrolidine derivatives as deubiquitylating enzymes (dub) inhibitors

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20200114

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20200114

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20210105

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20201224

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20210402

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20210322

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20210706

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20210802

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20210907

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20211007

R150 Certificate of patent or registration of utility model

Ref document number: 6959247

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250