CN115968288A - 作为ret激酶抑制剂的杂芳环化合物及其制备和应用 - Google Patents

作为ret激酶抑制剂的杂芳环化合物及其制备和应用 Download PDF

Info

Publication number
CN115968288A
CN115968288A CN202180051059.1A CN202180051059A CN115968288A CN 115968288 A CN115968288 A CN 115968288A CN 202180051059 A CN202180051059 A CN 202180051059A CN 115968288 A CN115968288 A CN 115968288A
Authority
CN
China
Prior art keywords
alkyl
compound
pharmaceutically acceptable
alkoxy
solvate
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
CN202180051059.1A
Other languages
English (en)
Inventor
朱永强
刘兆刚
冯超
陈浩
徐锴锴
王佳
石晶淼
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.)
Jiangsu Chia Tai Fenghai Pharmaceutical Co Ltd
Original Assignee
Jiangsu Chia Tai Fenghai Pharmaceutical 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 Jiangsu Chia Tai Fenghai Pharmaceutical Co Ltd filed Critical Jiangsu Chia Tai Fenghai Pharmaceutical Co Ltd
Publication of CN115968288A publication Critical patent/CN115968288A/zh
Pending legal-status Critical Current

Links

Classifications

    • 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
    • C07D487/08—Bridged systems
    • 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
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • 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
    • A61K31/496—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
    • A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • 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
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明公开了作为RET激酶抑制剂的杂芳环化合物及其制备和应用，化合物为具有式(I)结构的化合物或其药学上可接受的盐，这些化合物或其盐可通过靶向RET基因融合及突变形式的受体，而用于疾病或病况的治疗或预防，可以有效抑制多种肿瘤细胞的生长，并对RET基因融合突变及其它蛋白酶产生抑制作用，可用于制备抗肿瘤药物。

Description

PCT国内申请，说明书已公开。

Claims (18)

  1. PCT国内申请，权利要求书已公开。
CN202180051059.1A 2020-08-20 2021-08-19 作为ret激酶抑制剂的杂芳环化合物及其制备和应用 Pending CN115968288A (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
CN2020108438236 2020-08-20
CN202010843823 2020-08-20
CN2020112365223 2020-11-09
CN202011236522 2020-11-09
CN2021104319054 2021-04-21
CN202110431905 2021-04-21
PCT/CN2021/113514 WO2022037643A1 (zh) 2020-08-20 2021-08-19 作为ret激酶抑制剂的杂芳环化合物及其制备和应用

Publications (1)

Publication Number Publication Date
CN115968288A true CN115968288A (zh) 2023-04-14

Family

ID=80322588

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202180051059.1A Pending CN115968288A (zh) 2020-08-20 2021-08-19 作为ret激酶抑制剂的杂芳环化合物及其制备和应用

Country Status (8)

Country Link
US (1) US20230322769A1 (zh)
EP (1) EP4201936A4 (zh)
JP (1) JP2023538096A (zh)
KR (1) KR20230054425A (zh)
CN (1) CN115968288A (zh)
AU (1) AU2021326917A1 (zh)
CA (1) CA3191183A1 (zh)
WO (1) WO2022037643A1 (zh)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114805286B (zh) * 2022-05-06 2023-06-16 深圳职业技术学院 一种萘并氧硫杂卓类衍生物的制备方法
CN115028603A (zh) * 2022-06-17 2022-09-09 安庆朗坤药业有限公司 一种n-甲基-d3-哌嗪盐酸盐的制备方法

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LT3322706T (lt) * 2015-07-16 2021-03-10 Array Biopharma, Inc. Pakeistieji pirazolo[1,5-a]piridino junginiai, kaip ret kinazės inhibitoriai
KR20210070286A (ko) * 2018-09-30 2021-06-14 베이징 즈지엔진루이 셩우이야오 커지 요우시엔공스 치환된 피라졸 융합고리계 유도체 및 이의 제조 방법과 응용
US20220017539A1 (en) * 2018-12-06 2022-01-20 Shenzhen Targetrx, Inc. Substituted pyrazolo[1,5-a]pyridine compound, composition containing the same and use thereof
EP3950685A4 (en) * 2019-04-03 2022-12-14 Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd. Baiyunshan Pharmaceutical General Factory PYRAZOLOPYRIDINE COMPOUND USED AS RET INHIBITOR AND USES THEREOF
US20220259201A1 (en) * 2019-05-14 2022-08-18 Shanghai Hansoh Biomedical Co., Ltd. Inhibitor containing bicyclic derivative, preparation method therefor and use thereof
EP3980425A1 (en) * 2019-06-10 2022-04-13 JS InnoPharm (Shanghai) Ltd. Heterocyclic compounds as kinase inhibitors, compositions comprising the heterocyclic compound, and methods of use thereof
CN112778337B (zh) * 2019-11-08 2023-09-26 杭州邦顺制药有限公司 作为ret激酶抑制剂的3、6二氮杂双环[3.1.1]庚烷衍生物
CN112851664B (zh) * 2019-11-12 2024-03-29 浙江海正药业股份有限公司 吡唑[1,5-a]吡啶-3-腈化合物及其在医药上的用途
CN111269229B (zh) * 2020-03-27 2021-02-12 苏州信诺维医药科技有限公司 一种治疗癌症的化合物

Also Published As

Publication number Publication date
JP2023538096A (ja) 2023-09-06
AU2021326917A9 (en) 2024-06-20
AU2021326917A1 (en) 2023-05-04
CA3191183A1 (en) 2022-02-24
EP4201936A4 (en) 2024-02-21
US20230322769A1 (en) 2023-10-12
WO2022037643A1 (zh) 2022-02-24
KR20230054425A (ko) 2023-04-24
EP4201936A1 (en) 2023-06-28

Similar Documents

Publication Publication Date Title
US11845760B2 (en) PRMT5 inhibitors
WO2018022761A1 (en) Substituted cyclopentane-amides for treating disorders related to ret
WO2017161269A1 (en) Inhibitors of ret receptor tyrosine kinases
CN109415361B (zh) 丙烯酸类衍生物及其制备方法和其在医药上的用途
CN115968288A (zh) 作为ret激酶抑制剂的杂芳环化合物及其制备和应用
EP3768671B1 (en) Substituted imidazolidin-2-one derivatives as prmt5 inhibitors
CN108349896A (zh) 作为fgfr抑制剂的杂环化合物
CN113321654A (zh) 作为激酶抑制剂的稠合吡啶酮类化合物
CN110461849B (zh) 一种csf1r抑制剂及其制备方法和应用
TW201605858A (zh) 縮合吡唑衍生物
CN116600808A (zh) 一类作为kras突变体g12c抑制剂的四氢萘啶类衍生物、其制备方法及其应用
CN107759522B (zh) 羧酸类衍生物、其制备方法及其在医药上的用途
KR20230005227A (ko) Trpv4 길항제로서의 피리미딘-4(3h)-온 유도체
WO2022272106A1 (en) Cdk2 inhibitors and methods of using the same
KR20230107542A (ko) 헤테로방향족 화합물 및 이의 용도
CN115843296A (zh) Cdk9抑制剂及其用途
WO2024051631A1 (zh) 一种大环咪唑并[1,2-b]哒嗪衍生物及其制备方法和用途
EP4342895A1 (en) Heteroaryl derivative compound and use thereof
TW202415660A (zh) 三嗪類化合物及其用途
TW202312995A (zh) 氮雜芳基化合物、其製備方法及應用
EA046513B1 (ru) Замещенные производные имидазолидин-2-она в качестве ингибиторов prmt5

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