CN115244053A - 靶向蛋白降解化合物及其制备方法和应用 - Google Patents

靶向蛋白降解化合物及其制备方法和应用 Download PDF

Info

Publication number
CN115244053A
CN115244053A CN202180018078.4A CN202180018078A CN115244053A CN 115244053 A CN115244053 A CN 115244053A CN 202180018078 A CN202180018078 A CN 202180018078A CN 115244053 A CN115244053 A CN 115244053A
Authority
CN
China
Prior art keywords
alkyl
cycloalkyl
optionally substituted
membered
halogen
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.)
Granted
Application number
CN202180018078.4A
Other languages
English (en)
Other versions
CN115244053B (zh
Inventor
冯焱
李世强
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.)
Shanghai Lingtai Biomedical Technology Co ltd
Original Assignee
Shanghai Lingtai Biomedical Technology Co 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 Shanghai Lingtai Biomedical Technology Co ltd filed Critical Shanghai Lingtai Biomedical Technology Co ltd
Priority to CN202410106573.6A priority Critical patent/CN117964623A/zh
Publication of CN115244053A publication Critical patent/CN115244053A/zh
Application granted granted Critical
Publication of CN115244053B publication Critical patent/CN115244053B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • C07D401/10—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 aromatic 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
    • A61K31/435—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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/505—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

本发明提供了一类靶向IRAK4激酶蛋白降解的双功能化合物、药物组合物及其制备方法。本发明所述化合物不但能够有效的抑制和/或降解细胞中的IRAK4激酶蛋白，能有效的抑制免疫细胞产生IL‑6，且具有很好的降解选择性。可用作制备治疗和/或预防由IRAK4介导的相关疾病或病症的药物，如癌症、免疫性疾病和炎性疾病。

Description

PCT国内申请，说明书已公开。

Claims (33)

  1. PCT国内申请，权利要求书已公开。
CN202180018078.4A 2020-08-05 2021-08-05 靶向蛋白降解化合物及其制备方法和应用 Active CN115244053B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202410106573.6A CN117964623A (zh) 2020-08-05 2021-08-05 靶向蛋白降解化合物及其制备方法和应用

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN202010785541 2020-08-05
CN2020107855415 2020-08-05
CN202011513669 2020-12-18
CN2020115136692 2020-12-18
PCT/CN2021/110990 WO2022028547A1 (zh) 2020-08-05 2021-08-05 靶向蛋白降解化合物及其制备方法和应用

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN202410106573.6A Division CN117964623A (zh) 2020-08-05 2021-08-05 靶向蛋白降解化合物及其制备方法和应用

Publications (2)

Publication Number Publication Date
CN115244053A true CN115244053A (zh) 2022-10-25
CN115244053B CN115244053B (zh) 2024-01-30

Family

ID=80117051

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202410106573.6A Pending CN117964623A (zh) 2020-08-05 2021-08-05 靶向蛋白降解化合物及其制备方法和应用
CN202180018078.4A Active CN115244053B (zh) 2020-08-05 2021-08-05 靶向蛋白降解化合物及其制备方法和应用

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN202410106573.6A Pending CN117964623A (zh) 2020-08-05 2021-08-05 靶向蛋白降解化合物及其制备方法和应用

Country Status (12)

Country Link
US (1) US20230234936A1 (zh)
EP (1) EP4194457A1 (zh)
JP (1) JP2023530848A (zh)
KR (1) KR20230050375A (zh)
CN (2) CN117964623A (zh)
AU (1) AU2021323304A1 (zh)
BR (1) BR112023002112A2 (zh)
CA (1) CA3188258A1 (zh)
MX (1) MX2023001566A (zh)
TW (1) TWI833104B (zh)
WO (1) WO2022028547A1 (zh)
ZA (1) ZA202301449B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117024413A (zh) * 2023-10-07 2023-11-10 天津匠新致成科技有限公司 3-氨基吡嗪-2-甲酰胺类靶向蛋白水解嵌合体及其制备方法、药物组合物和应用

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20240052795A (ko) * 2021-08-23 2024-04-23 상하이 리딩택 파마슈티컬 코., 엘티디. Irak4 분해제 및 이의 제조방법과 응용
WO2024094190A1 (zh) * 2022-11-04 2024-05-10 上海领泰生物医药科技有限公司 Irak4降解剂及其用途

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109563076A (zh) * 2016-08-18 2019-04-02 葛兰素史克知识产权开发有限公司 新型化合物
WO2019099926A1 (en) * 2017-11-17 2019-05-23 Arvinas, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides
CN110612294A (zh) * 2017-01-31 2019-12-24 阿尔维纳斯运营股份有限公司 人小脑蛋白配体和包含其的双官能化合物

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3727428A1 (en) 2017-12-20 2020-10-28 Translate Bio, Inc. Improved composition and methods for treatment of ornithine transcarbamylase deficiency
EP3752504A4 (en) 2018-02-14 2021-06-09 Dana Farber Cancer Institute, Inc. COMPOUNDS DEGRADING THE IRAQ AND USES OF THESE LATEST
KR20210111252A (ko) 2018-11-30 2021-09-10 카이메라 쎄라퓨틱스 인코포레이티드 Irak 분해제 및 이의 용도

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109563076A (zh) * 2016-08-18 2019-04-02 葛兰素史克知识产权开发有限公司 新型化合物
CN110612294A (zh) * 2017-01-31 2019-12-24 阿尔维纳斯运营股份有限公司 人小脑蛋白配体和包含其的双官能化合物
WO2019099926A1 (en) * 2017-11-17 2019-05-23 Arvinas, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117024413A (zh) * 2023-10-07 2023-11-10 天津匠新致成科技有限公司 3-氨基吡嗪-2-甲酰胺类靶向蛋白水解嵌合体及其制备方法、药物组合物和应用
CN117024413B (zh) * 2023-10-07 2024-01-09 天津匠新致成科技有限公司 3-氨基吡嗪-2-甲酰胺类靶向蛋白水解嵌合体及其制备方法、药物组合物和应用

Also Published As

Publication number Publication date
ZA202301449B (en) 2024-06-26
AU2021323304A1 (en) 2023-03-02
CN115244053B (zh) 2024-01-30
CN117964623A (zh) 2024-05-03
MX2023001566A (es) 2023-04-13
CA3188258A1 (en) 2022-02-10
BR112023002112A2 (pt) 2023-04-18
EP4194457A1 (en) 2023-06-14
KR20230050375A (ko) 2023-04-14
JP2023530848A (ja) 2023-07-20
TW202210470A (zh) 2022-03-16
US20230234936A1 (en) 2023-07-27
TWI833104B (zh) 2024-02-21
WO2022028547A1 (zh) 2022-02-10

Similar Documents

Publication Publication Date Title
CN109983007B (zh) 酰胺类衍生物抑制剂及其制备方法和应用
CN115244053A (zh) 靶向蛋白降解化合物及其制备方法和应用
JP2019532995A (ja) タウタンパク質標的化ｐｒｏｔａｃ、および関連使用方法
CN112778276A (zh) 作为shp2抑制剂的化合物及其应用
CN110494433B (zh) 布鲁顿酪氨酸激酶抑制剂
CN112390797A (zh) 新型螺环类K-Ras G12C抑制剂
CN113748114A (zh) 一种喹唑啉化合物及其在医药上的应用
WO2021115457A1 (zh) 吡唑并[1,5-a]吡啶类化合物及其制备方法和应用
JP6314147B2 (ja) 選択的ｐａｒｐ−１阻害剤としての４−カルボキサミド−イソインドリノン誘導体
CN115244042A (zh) 吲唑类衍生物及其制备方法和应用
WO2022012409A1 (zh) 一种rock抑制剂及其制备方法和用途
KR20230051528A (ko) 화합물, 조성물 및 방법
CN111630058B (zh) 吡喃葡萄糖基衍生物及其用途
WO2021083383A1 (zh) 一类含氮稠环类sting调节剂类化合物、制备方法和用途
JP7282743B2 (ja) 複素環化合物
TWI833193B (zh) 二唑化合物及含彼的藥學組成物
WO2022148459A1 (zh) 一类新型Smad3蛋白降解剂及其应用
WO2023025159A1 (zh) Irak4降解剂及其制备方法和应用
WO2022174765A1 (zh) 作为Wee-1抑制剂的稠环化合物
WO2024140319A1 (zh) 一种嘧啶类化合物及其制备方法和医药用途
WO2023236960A1 (zh) 一种具有rsk抑制作用的羧酰胺衍生物、包含其的药物组合物及其用途
WO2023160614A1 (zh) 作为fak抑制剂的化合物及其用途
CN118255760A (zh) 一种嘧啶类化合物及其制备方法和医药用途
KR20240004539A (ko) Wee-1 억제제로서의 축합 고리 화합물, 그를 위한 제조 방법 및 그의 용도
TW202421134A (zh) 治療癌症之方法

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
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40082792

Country of ref document: HK

GR01 Patent grant
GR01 Patent grant