CN113395965A - 用于治疗的usp19抑制剂 - Google Patents

用于治疗的usp19抑制剂 Download PDF

Info

Publication number
CN113395965A
CN113395965A CN201980091404.7A CN201980091404A CN113395965A CN 113395965 A CN113395965 A CN 113395965A CN 201980091404 A CN201980091404 A CN 201980091404A CN 113395965 A CN113395965 A CN 113395965A
Authority
CN
China
Prior art keywords
methyl
hydroxy
phenyl
oxo
dihydropyridine
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.)
Pending
Application number
CN201980091404.7A
Other languages
English (en)
Chinese (zh)
Inventor
詹姆士·塞缪尔·沙恩·朗特里
P·休伊特
M·M·麦克法兰
弗兰克·布尔坎普
C·贝尔
科林·奥多德
蒂莫西·哈里森
M·D·赫尔姆
E·罗兹卡
A·克兰斯顿
X·雅克
L·普罗克特
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Almac Discovery Ltd
Original Assignee
Almac Discovery 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
Priority claimed from GBGB1819936.4A external-priority patent/GB201819936D0/en
Priority claimed from GBGB1904341.3A external-priority patent/GB201904341D0/en
Application filed by Almac Discovery Ltd filed Critical Almac Discovery Ltd
Publication of CN113395965A publication Critical patent/CN113395965A/zh
Pending legal-status Critical Current

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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • C07D401/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • 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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201980091404.7A 2018-12-06 2019-12-06 用于治疗的usp19抑制剂 Pending CN113395965A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GBGB1819936.4A GB201819936D0 (en) 2018-12-06 2018-12-06 Therapeutic methods
GB1819936.4 2018-12-06
GBGB1904341.3A GB201904341D0 (en) 2019-03-28 2019-03-28 Therapeutic methods
GB1904341.3 2019-03-28
PCT/GB2019/053456 WO2020115500A1 (en) 2018-12-06 2019-12-06 Usp19 inhibitors for use in therapy

Publications (1)

Publication Number Publication Date
CN113395965A true CN113395965A (zh) 2021-09-14

Family

ID=68887434

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980091404.7A Pending CN113395965A (zh) 2018-12-06 2019-12-06 用于治疗的usp19抑制剂

Country Status (12)

Country Link
US (1) US20220016115A1 (https=)
EP (1) EP3890737B1 (https=)
JP (1) JP2022510700A (https=)
KR (1) KR20210100127A (https=)
CN (1) CN113395965A (https=)
AU (1) AU2019393161A1 (https=)
BR (1) BR112021010645A2 (https=)
CA (1) CA3121422A1 (https=)
IL (1) IL283687A (https=)
MX (1) MX2021006542A (https=)
SG (1) SG11202105911PA (https=)
WO (1) WO2020115500A1 (https=)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3965749A4 (en) * 2019-05-06 2023-06-21 Valo Health, Inc. ESCAPEMENT OF USP19
GB202104097D0 (en) 2021-03-24 2021-05-05 Almac Discovery Ltd Pharmaceutical compounds
GB202311227D0 (en) 2023-07-21 2023-09-06 Almac Discovery Ltd Pharmaceutical compounds

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104174021A (zh) * 2013-05-22 2014-12-03 复旦大学附属华山医院 蛋白酶体抑制剂在制备治疗慢性低度炎症性疾病药物中的用途
WO2018020242A1 (en) * 2016-07-26 2018-02-01 Almac Discovery Limited Pharmaceutical compounds
CN112135818A (zh) * 2018-01-31 2020-12-25 阿尔麦克探索有限公司 4-羟基哌啶衍生物及其作为泛素特异性蛋白酶19(usp19)的抑制剂的用途

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPO111096A0 (en) * 1996-07-18 1996-08-08 Fujisawa Pharmaceutical Co., Ltd. New compound
TW200930713A (en) 2007-12-03 2009-07-16 Takeda Pharmaceutical Nitrogen-containing heterocyclic compound and use thereof
AR103297A1 (es) * 2014-12-30 2017-05-03 Forma Therapeutics Inc Pirrolo y pirazolopirimidinas como inhibidores de la proteasa 7 específica de ubiquitina
CA3072353A1 (en) * 2017-09-26 2019-04-04 Dana-Farber Cancer Institute, Inc. Usp7 inhibitors for treating multiple myeloma

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104174021A (zh) * 2013-05-22 2014-12-03 复旦大学附属华山医院 蛋白酶体抑制剂在制备治疗慢性低度炎症性疾病药物中的用途
WO2018020242A1 (en) * 2016-07-26 2018-02-01 Almac Discovery Limited Pharmaceutical compounds
CN109790146A (zh) * 2016-07-26 2019-05-21 阿尔麦克探索有限公司 药物化合物
CN112135818A (zh) * 2018-01-31 2020-12-25 阿尔麦克探索有限公司 4-羟基哌啶衍生物及其作为泛素特异性蛋白酶19(usp19)的抑制剂的用途

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ERIN S. COYNE等: ""Knockout of USP19 Deubiquitinating Enzyme Prevents Muscle Wasting by Modulating Insulin and Glucocorticoid Signaling"", 《ENDOCRINOLOGY》 *
ERIN S. COYNE等: ""The deubiquitinating enzyme USP19 modulates adipogenesis and potentiates high-fat-diet-induced obesity and glucose intolerance in mice"", 《DIABETOLOGIA》 *

Also Published As

Publication number Publication date
JP2022510700A (ja) 2022-01-27
WO2020115500A1 (en) 2020-06-11
EP3890737A1 (en) 2021-10-13
IL283687A (en) 2021-07-29
BR112021010645A2 (pt) 2021-08-17
MX2021006542A (es) 2021-07-07
CA3121422A1 (en) 2020-06-11
US20220016115A1 (en) 2022-01-20
EP3890737B1 (en) 2024-06-05
SG11202105911PA (en) 2021-07-29
KR20210100127A (ko) 2021-08-13
AU2019393161A1 (en) 2021-06-17

Similar Documents

Publication Publication Date Title
JP2026017550A (ja) 急速進行性線維肉腫ポリペプチドの標的分解のための多環式化合物および方法
JP6986065B2 (ja) 医薬化合物
CA2819889C (en) Substituted pyridinone-pyridinyl compounds
EP3510025A1 (en) Heteroaryl inhibitors of pad4
RU2645711C2 (ru) Блокаторы натриевых каналов, способ их получения и их применение
AU2016232191B2 (en) NK-3 receptor antagonists for therapeutic or cosmetic treatment of excess body fat
WO2019014427A1 (en) ANTAGONISTS OF THE MUSCARINIC RECEPTOR OF ACETYLCHOLINE M4
US10875863B2 (en) RIPK2 inhibitors and method of treating cancer with same
KR20060008903A (ko) Ｍ기 키네신 저해제
JP2016529249A (ja) 置換ピラゾロ［１，５−ａ］ピリジン−３−カルボキサミドおよびその使用
CN113395965A (zh) 用于治疗的usp19抑制剂
CN106715426A (zh) 氰基取代的咪唑并[1,2‑a]吡啶甲酰胺及其用途
TW202038950A (zh) 作為Nav1.7及Nav1.8阻斷劑之雜環衍生物
CN106029656A (zh) 羟吲哚衍生物、其制备及其在治疗ampk相关疾病中的治疗用途
WO2016088813A1 (ja) 新規ジアザビシクロ［２．２．２］オクタン誘導体
CN103261193A (zh) 抑制白三烯生成的*二唑抑制剂
US20220033397A1 (en) Pharmaceutical compounds and their use as inhibitors of ubiquitin specific protease 19 (usp19)
JP7808733B2 (ja) 置換オキソイソインドリニルピペリジン－２，６－ジオン化合物
TW201022234A (en) Pyrrolidines
JP4221294B2 (ja) 摂食亢進剤および食欲不振症治療剤
AU2024300899A1 (en) Pharmaceutical compounds
WO2025108404A1 (zh) 一种靶向降解雄激素受体的双功能嵌合体的杂环化合物及其用途
WO2025108406A1 (zh) 一种靶向降解雄激素受体的双功能嵌合体的杂环化合物及其用途
AU2011265521B9 (en) JNK inhibitors for the treatment of endometreosis
CN119384408A (zh) 用于靶向蛋白降解的双功能分子

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20210914