MX387482B - Derivados de n-cianopirrolidina de fórmula (i) con actividad como inhibidores de la peptidasa específica de ubiquitina (usp30). - Google Patents

Derivados de n-cianopirrolidina de fórmula (i) con actividad como inhibidores de la peptidasa específica de ubiquitina (usp30).

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Publication number
MX387482B
MX387482B MX2018007449A MX2018007449A MX387482B MX 387482 B MX387482 B MX 387482B MX 2018007449 A MX2018007449 A MX 2018007449A MX 2018007449 A MX2018007449 A MX 2018007449A MX 387482 B MX387482 B MX 387482B
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Mexico
Prior art keywords
sup
ubiquitin
usp30
formula
activity
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Application number
MX2018007449A
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English (en)
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MX2018007449A (es
Inventor
Mark Ian Kemp
Andrew Madin
Martin Lee Stockley
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Mission Therapeutics Ltd
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Publication date
Application filed by Mission Therapeutics Ltd filed Critical Mission Therapeutics Ltd
Publication of MX2018007449A publication Critical patent/MX2018007449A/es
Publication of MX387482B publication Critical patent/MX387482B/es

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    • 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
    • A61K31/40—Heterocyclic 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
    • A61K31/4025—Heterocyclic 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
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/40—Heterocyclic 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
    • A61K31/407—Heterocyclic 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 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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    • A61P25/16—Anti-Parkinson drugs
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    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D413/02—Heterocyclic 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
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    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
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    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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    • 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
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    • C07D487/04—Ortho-condensed systems

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  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyrrole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La presente invención se refiere a compuestos novedosos y a métodos para la fabricación de inhibidores de enzimas desubiquitinantes (DUB); en particular, la invención se refiere a la inhibición de la hidrolasa 30 de la C-terminal de la ubiquitina o Peptidasa 30 Específica de Ubiquitina (USP30); la invención se refiere además al uso de los inhibidores de DUB en el tratamiento de condiciones que involucran disfunción mitocondrial y cáncer; los compuestos de la invención incluyen compuestos que tienen la Fórmula (I): (ver Fórmula) o una sal farmacéuticamente aceptable de los mismos, en donde R1a, R1b, R1c, R1d, R1e, R1f, R1g, R2, X, L y A son como se definieron en la presente.
MX2018007449A 2015-12-17 2016-12-16 Derivados de n-cianopirrolidina de fórmula (i) con actividad como inhibidores de la peptidasa específica de ubiquitina (usp30). MX387482B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB1522267.2A GB201522267D0 (en) 2015-12-17 2015-12-17 Novel compounds
PCT/GB2016/053971 WO2017103614A1 (en) 2015-12-17 2016-12-16 Novel Compounds

Publications (2)

Publication Number Publication Date
MX2018007449A MX2018007449A (es) 2018-11-09
MX387482B true MX387482B (es) 2025-03-18

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MX2018007449A MX387482B (es) 2015-12-17 2016-12-16 Derivados de n-cianopirrolidina de fórmula (i) con actividad como inhibidores de la peptidasa específica de ubiquitina (usp30).

Country Status (19)

Country Link
US (2) US11130748B2 (es)
EP (2) EP3390391B1 (es)
JP (1) JP6898327B2 (es)
KR (1) KR102663994B1 (es)
CN (1) CN108368089B (es)
AU (1) AU2016373533B2 (es)
BR (1) BR112018007208B1 (es)
CA (1) CA3008747C (es)
CO (1) CO2018006299A2 (es)
ES (1) ES2929376T3 (es)
GB (1) GB201522267D0 (es)
IL (1) IL258444B (es)
MA (1) MA44050A (es)
MX (1) MX387482B (es)
MY (1) MY196729A (es)
RU (1) RU2734256C2 (es)
SG (1) SG11201804934PA (es)
WO (1) WO2017103614A1 (es)
ZA (1) ZA201804739B (es)

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HRP20210791T2 (hr) 2015-03-30 2021-12-10 Mission Therapeutics Limited 1-cijano-pirolidin spojevi kao usp30 inhibitori
CN107849013B (zh) 2015-07-14 2022-03-29 特殊治疗有限公司 作为dub抑制剂用于治疗癌症的氰基吡咯烷类
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
EP3433246B1 (en) 2016-03-24 2022-05-04 Mission Therapeutics Limited 1-cyano-pyrrolidine derivatives as dbu inhibitors
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
CN110831936B (zh) * 2017-06-20 2023-03-28 特殊治疗有限公司 具有dub抑制剂活性的取代氰基吡咯烷
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GB2571731A (en) * 2018-03-06 2019-09-11 Mission Therapeutics Ltd Novel compounds and uses
WO2019180686A1 (en) * 2018-03-23 2019-09-26 Cmg Pharmaceutical Co., Ltd. Ido-tdo dual inhibitor and related methods of use
ES2988920T3 (es) * 2018-05-17 2024-11-22 Forma Therapeutics Inc Compuestos bicíclicos fusionados útiles como inhibidores de la peptidasa 30 específica de ubiquitina
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AU2019356011B2 (en) * 2018-10-05 2025-02-06 Forma Therapeutics, Inc. Fused pyrrolines which act as Ubiquitin-Specific Protease 30 (USP30) inhibitors
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
WO2021200934A1 (ja) * 2020-03-30 2021-10-07 国立大学法人 長崎大学 抗マラリア薬
MX2022012578A (es) 2020-04-08 2022-11-07 Mission Therapeutics Ltd N-cianopirrolidinas con actividad como inhibidores de usp30.
EP4157834B1 (en) * 2020-05-28 2024-07-03 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
IL298710A (en) * 2020-06-04 2023-02-01 Mission Therapeutics Ltd 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
WO2023099561A1 (en) 2021-12-01 2023-06-08 Mission Therapeutics Limited Substituted n-cyanopyrrolidines with activity as usp30 inhibitors
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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CN107849013B (zh) 2015-07-14 2022-03-29 特殊治疗有限公司 作为dub抑制剂用于治疗癌症的氰基吡咯烷类
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
EP3433246B1 (en) 2016-03-24 2022-05-04 Mission Therapeutics Limited 1-cyano-pyrrolidine derivatives as dbu inhibitors
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
CN110831936B (zh) * 2017-06-20 2023-03-28 特殊治疗有限公司 具有dub抑制剂活性的取代氰基吡咯烷

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SG11201804934PA (en) 2018-07-30
JP6898327B2 (ja) 2021-07-07
BR112018007208B1 (pt) 2024-01-23
EP3390391A1 (en) 2018-10-24
RU2734256C2 (ru) 2020-10-13
RU2018123779A3 (es) 2020-02-18
CN108368089B (zh) 2021-07-06
AU2016373533A1 (en) 2018-07-05
CN108368089A (zh) 2018-08-03
US11130748B2 (en) 2021-09-28
CA3008747A1 (en) 2017-06-22
KR20180095625A (ko) 2018-08-27
CA3008747C (en) 2023-06-13
AU2016373533B2 (en) 2020-06-11
MY196729A (en) 2023-05-03
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US11958833B2 (en) 2024-04-16
IL258444A (en) 2018-05-31
US20210380562A1 (en) 2021-12-09
US20200172516A1 (en) 2020-06-04
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GB201522267D0 (en) 2016-02-03
ES2929376T3 (es) 2022-11-28
WO2017103614A1 (en) 2017-06-22
CO2018006299A2 (es) 2018-07-10
MX2018007449A (es) 2018-11-09
EP3390391B1 (en) 2022-09-14
HK1256059A1 (zh) 2019-09-13
NZ741411A (en) 2022-03-25
MA44050A (fr) 2018-10-24
RU2018123779A (ru) 2020-01-17
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BR112018007208A2 (pt) 2018-10-16
IL258444B (en) 2020-08-31

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