CN115697990B - 基于吲唑的化合物和相关使用方法 - Google Patents

基于吲唑的化合物和相关使用方法 Download PDF

Info

Publication number
CN115697990B
CN115697990B CN202180035521.9A CN202180035521A CN115697990B CN 115697990 B CN115697990 B CN 115697990B CN 202180035521 A CN202180035521 A CN 202180035521A CN 115697990 B CN115697990 B CN 115697990B
Authority
CN
China
Prior art keywords
alkyl
optionally substituted
group
ptm
mixture
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
CN202180035521.9A
Other languages
English (en)
Chinese (zh)
Other versions
CN115697990A (zh
Inventor
埃里卡·阿劳乔
史蒂文·M·斯帕克斯
迈克尔·柏林
张伟
王静
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.)
Avenas Enterprises
Original Assignee
Avenas Enterprises
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 Avenas Enterprises filed Critical Avenas Enterprises
Publication of CN115697990A publication Critical patent/CN115697990A/zh
Application granted granted Critical
Publication of CN115697990B publication Critical patent/CN115697990B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K31/496—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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Psychology (AREA)
  • Immunology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN202180035521.9A 2020-03-21 2021-03-19 基于吲唑的化合物和相关使用方法 Active CN115697990B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202062992952P 2020-03-21 2020-03-21
US62/992,952 2020-03-21
PCT/US2021/023183 WO2021194879A1 (en) 2020-03-21 2021-03-19 Indazole based compounds and associated methods of use

Publications (2)

Publication Number Publication Date
CN115697990A CN115697990A (zh) 2023-02-03
CN115697990B true CN115697990B (zh) 2025-06-13

Family

ID=75539924

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202180035521.9A Active CN115697990B (zh) 2020-03-21 2021-03-19 基于吲唑的化合物和相关使用方法

Country Status (12)

Country Link
US (2) US12053469B2 (https=)
EP (1) EP4121422A1 (https=)
JP (2) JP7644139B2 (https=)
KR (1) KR20230004511A (https=)
CN (1) CN115697990B (https=)
AU (1) AU2021244180A1 (https=)
BR (1) BR112022018909A2 (https=)
CA (1) CA3172387A1 (https=)
CO (1) CO2022014718A2 (https=)
IL (1) IL296648A (https=)
MX (1) MX2022011674A (https=)
WO (1) WO2021194879A1 (https=)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10654809B2 (en) 2016-06-10 2020-05-19 University Of Tennessee Research Foundation Selective androgen receptor degrader (SARD) ligands and methods of use thereof
WO2019195609A2 (en) 2018-04-04 2019-10-10 Arvinas Operations, Inc. Modulators of proteolysis and associated methods of use
JP7644139B2 (ja) 2020-03-21 2025-03-11 アルヴィナス・オペレーションズ・インコーポレイテッド インダゾール系化合物及び関連使用方法
WO2021194878A1 (en) * 2020-03-21 2021-09-30 Arvinas Operations, Inc. Selective modulators of mutant lrrk2 proteolysis and associated methods of use
CN117321046A (zh) * 2021-03-19 2023-12-29 阿维纳斯企业公司 基于吲唑的化合物和相关使用方法
JP2024512501A (ja) * 2021-03-19 2024-03-19 アルヴィナス・オペレーションズ・インコーポレイテッド インダゾール系化合物及び関連使用方法
CA3235512A1 (en) * 2021-10-22 2023-04-27 Xiaobao Yang Crbn e3 ligase ligand compound, protein degrader developed based thereon and their applications
EP4276097A1 (en) 2022-05-10 2023-11-15 University Of Dundee Aminopyrimidinyl derivatives for the treament of parkinson's disease
WO2024010818A2 (en) * 2022-07-07 2024-01-11 University Of Tennessee Research Foundation Proteolysis targeting chimera (protac) of selective androgen receptor degrader (sard) compounds and methods of use thereof
WO2024054876A1 (en) * 2022-09-07 2024-03-14 Arvinas Operations, Inc. Leucine rich repeat kinase 2 (lrrk2) degrading compounds and associated methods of use
US12448399B2 (en) 2023-01-26 2025-10-21 Arvinas Operations, Inc. Cereblon-based KRAS degrading PROTACs and uses related thereto
WO2024173646A1 (en) * 2023-02-16 2024-08-22 Innovo Therapeutics, Inc. Cyclin-dependent kinase degrading compounds
WO2025056074A1 (zh) * 2023-09-14 2025-03-20 中国科学院上海药物研究所 杂环基取代的吲唑酮类化合物、其制备方法、药物组合物及其应用
TW202515874A (zh) 2023-09-28 2025-04-16 美商亞文納營運公司 用於靶向降解富含白胺酸之重複激酶２（ｌｒｒｋ２）的基於苯并咪唑及苯并咪唑酮之ｐｒｏｔａｃ化合物
WO2025123046A1 (en) 2023-12-07 2025-06-12 Arvinas Operations, Inc. Synthesis of leucine-rich repeat kinase 2 modulators
CN120787222A (zh) * 2024-02-04 2025-10-14 标新生物医药科技(上海)有限公司 基于取代的异吲哚啉酮新颖骨架化合物、含有其的双功能蛋白降解剂及它们的应用
CN118344284A (zh) * 2024-03-06 2024-07-16 杭州医学院 一种具有苯甲酰胺结构的化合物及其制备方法和应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112888460A (zh) * 2018-10-16 2021-06-01 达纳-法伯癌症研究所有限公司 Lrkk2的野生型及突变型的降解剂

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
ES2577829T3 (es) 2010-06-04 2016-07-19 F. Hoffmann-La Roche Ag Derivados de aminopirimidina como moduladores de la LRRK2
KR102668696B1 (ko) 2012-01-12 2024-05-29 예일 유니버시티 E3 유비퀴틴 리가아제에 의한 표적 단백질 및 다른 폴리펩티드의 증진된 분해를 위한 화합물 및 방법
WO2014134774A1 (en) 2013-03-04 2014-09-12 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
WO2014134776A1 (en) 2013-03-04 2014-09-12 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
US9718818B2 (en) 2013-08-22 2017-08-01 Merck Sharp & Dohme Corp. Compounds inhibiting leucine-rich repeat kinase enzyme activity
US20160058872A1 (en) 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
US20180228907A1 (en) 2014-04-14 2018-08-16 Arvinas, Inc. Cereblon ligands and bifunctional compounds comprising the same
RU2738833C9 (ru) 2014-04-14 2022-02-28 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
MX2019005007A (es) * 2016-11-01 2019-07-18 Arvinas Inc Protac dirigidos a la proteína tau y métodos asociados de uso.
AU2018219292B2 (en) * 2017-02-08 2024-09-26 Dana-Farber Cancer Institute, Inc. Tunable endogenous protein degradation with heterobifunctional compounds
WO2019060742A1 (en) 2017-09-22 2019-03-28 Kymera Therapeutics, Inc AGENTS FOR DEGRADING PROTEINS AND USES THEREOF
IL302595A (en) 2018-04-13 2023-07-01 Arvinas Operations Inc Servalon ligands and bifunctional compounds containing them
US20210261553A1 (en) 2018-05-15 2021-08-26 E-Scape Bio, Inc. Fused tetrazoles as lrrk2 inhibitors
JP7297053B2 (ja) * 2018-08-20 2023-06-23 アルビナス・オペレーションズ・インコーポレイテッド 神経変性疾患を治療するためのｅ３ユビキチンリガーゼ結合活性を有するキメラ（ｐｒｏｔａｃ）化合物を標的とし、アルファ－シヌクレインタンパク質を標的とするタンパク質分解
US20230219945A1 (en) 2019-12-17 2023-07-13 Kymera Therapeutics, Inc. Irak degraders and uses thereof
JP7644139B2 (ja) 2020-03-21 2025-03-11 アルヴィナス・オペレーションズ・インコーポレイテッド インダゾール系化合物及び関連使用方法
WO2021194878A1 (en) * 2020-03-21 2021-09-30 Arvinas Operations, Inc. Selective modulators of mutant lrrk2 proteolysis and associated methods of use
JP2024512501A (ja) * 2021-03-19 2024-03-19 アルヴィナス・オペレーションズ・インコーポレイテッド インダゾール系化合物及び関連使用方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112888460A (zh) * 2018-10-16 2021-06-01 达纳-法伯癌症研究所有限公司 Lrkk2的野生型及突变型的降解剂

Also Published As

Publication number Publication date
WO2021194879A1 (en) 2021-09-30
US12053469B2 (en) 2024-08-06
CO2022014718A2 (es) 2022-10-31
KR20230004511A (ko) 2023-01-06
US20250114356A1 (en) 2025-04-10
CN115697990A (zh) 2023-02-03
EP4121422A1 (en) 2023-01-25
MX2022011674A (es) 2022-12-15
JP7644139B2 (ja) 2025-03-11
JP2023518830A (ja) 2023-05-08
JP2025078673A (ja) 2025-05-20
IL296648A (en) 2022-11-01
AU2021244180A1 (en) 2022-11-03
BR112022018909A2 (pt) 2022-12-13
US20210315896A1 (en) 2021-10-14
CA3172387A1 (en) 2021-09-30

Similar Documents

Publication Publication Date Title
CN115697990B (zh) 基于吲唑的化合物和相关使用方法
CN115605267B (zh) 突变体lrrk2蛋白水解的选择性调节剂和相关使用方法
CN114867727B (zh) Tau蛋白靶向化合物及相关使用方法
CN110234646B (zh) 靶向PROTAC的Tau蛋白及相关使用方法
US20230097358A1 (en) Indazole based compounds and associated methods of use
CN113493440A (zh) 含氮杂芳类衍生物的盐及其晶型
WO2006093247A1 (ja) Ｓｙｋ阻害活性を有する新規なアミノピリジン化合物
CN117321046A (zh) 基于吲唑的化合物和相关使用方法
WO2016139212A1 (en) Triazolopyridine compounds and methods of use thereof
KR102941832B1 (ko) Cdk9 억제제 및 이의 용도
OA21863A (en) Indazole based compounds and associated methods of use.
HK1245783A1 (en) Triazolopyridine compounds and methods of use thereof

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
GR01 Patent grant
GR01 Patent grant