MX2018007449A - Compuestos novedosos. - Google Patents

Compuestos novedosos.

Info

Publication number
MX2018007449A
MX2018007449A MX2018007449A MX2018007449A MX2018007449A MX 2018007449 A MX2018007449 A MX 2018007449A MX 2018007449 A MX2018007449 A MX 2018007449A MX 2018007449 A MX2018007449 A MX 2018007449A MX 2018007449 A MX2018007449 A MX 2018007449A
Authority
MX
Mexico
Prior art keywords
relates
compounds
novel compounds
inhibitors
ubiquitin
Prior art date
Application number
MX2018007449A
Other languages
English (en)
Inventor
Andrew Madin
Mark Ian Kemp
Lee Stockley Martin
Original Assignee
Mission Therapeutics Ltd
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 Mission Therapeutics Ltd filed Critical Mission Therapeutics Ltd
Publication of MX2018007449A publication Critical patent/MX2018007449A/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • 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
    • A61K31/40—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
    • 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
    • A61K31/40—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
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • 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
    • C07D413/12—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 linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D417/14—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
    • 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
    • C07D471/04—Ortho-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
    • C07D487/04—Ortho-condensed systems

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 Compuestos novedosos. MX2018007449A (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 (1)

Publication Number Publication Date
MX2018007449A true MX2018007449A (es) 2018-11-09

Family

ID=55311125

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2018007449A MX2018007449A (es) 2015-12-17 2016-12-16 Compuestos novedosos.

Country Status (19)

Country Link
US (2) US11130748B2 (es)
EP (2) EP3390391B1 (es)
JP (1) JP6898327B2 (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)
HK (1) HK1256059A1 (es)
IL (1) IL258444B (es)
MA (1) MA44050A (es)
MX (1) MX2018007449A (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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EP3943490A1 (en) 2015-03-30 2022-01-26 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
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
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
EP3793997B1 (en) * 2018-05-17 2024-03-13 Forma Therapeutics, Inc. Fused bicyclic compounds useful as ubiquitin-specific peptidase 30 inhibitors
US20210179628A1 (en) * 2018-08-09 2021-06-17 Valo Early Discovery, Inc. Inhibiting deubiquitinase usp25 and usp28
US11572374B2 (en) 2018-08-14 2023-02-07 Amgen Inc. N-cyano-7-azanorbornane derivatives and uses thereof
PL3860989T3 (pl) * 2018-10-05 2023-07-10 Forma Therapeutics, Inc. Sprzężone piroliny, które działają jako inhibitory proteazy 30 swoistej dla ubikwityny (usp30)
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
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 Development of n-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide and corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction
KR20230019198A (ko) 2020-06-04 2023-02-07 미션 테라퓨틱스 엘티디 Usp30 억제제로서의 활성을 갖는 n-시아노피롤리딘
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

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EP3943490A1 (en) 2015-03-30 2022-01-26 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
US11059809B2 (en) * 2017-06-20 2021-07-13 Mission Therapeutics Limited Substituted cyanopyrrolidines with activity as DUB inhibitors

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Publication number Publication date
AU2016373533B2 (en) 2020-06-11
CA3008747A1 (en) 2017-06-22
MA44050A (fr) 2018-10-24
BR112018007208A2 (pt) 2018-10-16
CN108368089A (zh) 2018-08-03
JP6898327B2 (ja) 2021-07-07
US20210380562A1 (en) 2021-12-09
WO2017103614A1 (en) 2017-06-22
CN108368089B (zh) 2021-07-06
EP3390391A1 (en) 2018-10-24
SG11201804934PA (en) 2018-07-30
US20200172516A1 (en) 2020-06-04
EP3390391B1 (en) 2022-09-14
BR112018007208B1 (pt) 2024-01-23
EP4122929A1 (en) 2023-01-25
KR20180095625A (ko) 2018-08-27
GB201522267D0 (en) 2016-02-03
RU2018123779A3 (es) 2020-02-18
US11130748B2 (en) 2021-09-28
HK1256059A1 (zh) 2019-09-13
US11958833B2 (en) 2024-04-16
AU2016373533A1 (en) 2018-07-05
RU2734256C2 (ru) 2020-10-13
NZ741411A (en) 2022-03-25
RU2018123779A (ru) 2020-01-17
JP2019504009A (ja) 2019-02-14
CO2018006299A2 (es) 2018-07-10
IL258444B (en) 2020-08-31
IL258444A (en) 2018-05-31
CA3008747C (en) 2023-06-13
MY196729A (en) 2023-05-03
ZA201804739B (en) 2020-01-29
ES2929376T3 (es) 2022-11-28

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