CN112739691A - 用作抗癌药的trk抑制剂 - Google Patents

用作抗癌药的trk抑制剂 Download PDF

Info

Publication number
CN112739691A
CN112739691A CN201980057263.7A CN201980057263A CN112739691A CN 112739691 A CN112739691 A CN 112739691A CN 201980057263 A CN201980057263 A CN 201980057263A CN 112739691 A CN112739691 A CN 112739691A
Authority
CN
China
Prior art keywords
compound
alkyl
optionally substituted
formula
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
CN201980057263.7A
Other languages
English (en)
Other versions
CN112739691B (zh
Inventor
仲伯禹
张彦涛
曹宜菊
陈光明
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.)
Taili Biotechnology Shanghai Co ltd
Original Assignee
Taili Biotechnology Shanghai 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 Taili Biotechnology Shanghai Co ltd filed Critical Taili Biotechnology Shanghai Co ltd
Publication of CN112739691A publication Critical patent/CN112739691A/zh
Application granted granted Critical
Publication of CN112739691B publication Critical patent/CN112739691B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

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
    • C07D487/06—Peri-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
    • C07D401/14—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
    • 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
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

涉及一组原肌球蛋白受体激酶抑制剂，其包含酰胺基苯氧基吲唑化合物结构。这些化合物对许多致癌激酶显示强效抑制作用，尤其是TRK，由此可用于治疗肿瘤或癌症。

Description

PCT国内申请，说明书已公开。

Claims (21)

  1. PCT国内申请，权利要求书已公开。
CN201980057263.7A 2018-09-03 2019-09-03 用作抗癌药的trk抑制剂 Active CN112739691B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201811019556 2018-09-03
CN201811019556X 2018-09-03
PCT/CN2019/104218 WO2020048455A1 (zh) 2018-09-03 2019-09-03 用作抗癌药的trk抑制剂

Publications (2)

Publication Number Publication Date
CN112739691A true CN112739691A (zh) 2021-04-30
CN112739691B CN112739691B (zh) 2023-05-23

Family

ID=69721561

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980057263.7A Active CN112739691B (zh) 2018-09-03 2019-09-03 用作抗癌药的trk抑制剂

Country Status (9)

Country Link
US (1) US11952364B2 (zh)
EP (1) EP3848365A4 (zh)
JP (1) JP7443373B2 (zh)
KR (1) KR20210054548A (zh)
CN (1) CN112739691B (zh)
AU (1) AU2019335450A1 (zh)
BR (1) BR112021004003A2 (zh)
CA (1) CA3111105A1 (zh)
WO (1) WO2020048455A1 (zh)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113121432A (zh) * 2021-04-16 2021-07-16 南京工业大学 一种带有导向基团的脂肪链烯烃的合成方法
WO2023062575A1 (en) * 2021-10-14 2023-04-20 Ideaya Biosciences, Inc. Cyclic vinyl sulfone compounds as wrn inhibitors

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010011538A1 (en) * 2008-07-24 2010-01-28 Eli Lilly And Company Amidophenoxyindazoles useful as inhibitors of c-met
WO2017027544A1 (en) * 2015-08-12 2017-02-16 Imclone Llc Combination therapy for cancer
WO2017180462A1 (en) * 2016-04-15 2017-10-19 Eli Lilly And Company Combination of ramucirumab and merestinib for use in treatment of colorectal cancer
WO2018022438A1 (en) * 2016-07-29 2018-02-01 Eli Lilly And Company Combination therapy with merestinib and anti-pd-l1 or anti-pd-1 inhibitors for use in the treatment of cancer
WO2018093669A1 (en) * 2016-11-16 2018-05-24 Eli Lilly And Company Combination therapy for cancer with exon 14 skipping mutation(s) or exon 14 skipping phenotype

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2007009842A (es) 2005-02-16 2007-08-23 Astrazeneca Ab Compuestos quimicos.
EP1877057A1 (en) 2005-04-27 2008-01-16 AstraZeneca AB Use of pyrazolyl-pyrimidine derivatives in the treatment of pain
CN101522682A (zh) 2006-10-30 2009-09-02 诺瓦提斯公司 作为抗炎剂的杂环化合物
WO2009136663A1 (en) 2008-05-08 2009-11-12 Takeda Pharmaceutical Company Limited Fused heterocyclic derivatives and use thereof
CN103965200B (zh) 2008-09-22 2016-06-08 阵列生物制药公司 作为trk激酶抑制剂的取代的咪唑并[1,2-b]哒嗪化合物
LT3372605T (lt) 2008-10-22 2022-02-10 Array Biopharma, Inc. Pakeistieji pirazolo[1,5-a]pirimidino junginiai, kaip trk kinazės inhibitoriai
JP2017532344A (ja) 2014-10-14 2017-11-02 デシファラ ファーマスーティカルズ， エルエルシー Ｔｒｋキナーゼ媒介性の腫瘍の増殖および疾患進行の阻害
AU2015355220B2 (en) 2014-12-02 2020-02-27 Ignyta, Inc. Combinations for the treatment of neuroblastoma
BR112018008357A2 (pt) 2015-10-26 2018-11-27 Array Biopharma Inc mutações de ponto em câncer resistente a inibidor de trk e métodos relacionados às mesmas
CN106649345A (zh) 2015-10-30 2017-05-10 微软技术许可有限责任公司 用于新闻的自动会话创建器

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010011538A1 (en) * 2008-07-24 2010-01-28 Eli Lilly And Company Amidophenoxyindazoles useful as inhibitors of c-met
WO2017027544A1 (en) * 2015-08-12 2017-02-16 Imclone Llc Combination therapy for cancer
WO2017180462A1 (en) * 2016-04-15 2017-10-19 Eli Lilly And Company Combination of ramucirumab and merestinib for use in treatment of colorectal cancer
WO2018022438A1 (en) * 2016-07-29 2018-02-01 Eli Lilly And Company Combination therapy with merestinib and anti-pd-l1 or anti-pd-1 inhibitors for use in the treatment of cancer
WO2018093669A1 (en) * 2016-11-16 2018-05-24 Eli Lilly And Company Combination therapy for cancer with exon 14 skipping mutation(s) or exon 14 skipping phenotype

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
FREDERICK MICHAEL O. ET AL.: "Development of an NH4Cl-Catalyzed Ethoxy Ethyl Deprotection in Flow for the Synthesis of Merestinib", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 *
KOSCIUCZUK EWA M. ET AL.: "Merestinib blocks Mnk kinase activity in acute myeloid leukemia progenitors and exhibits antileukemic effects in vitro and in vivo", 《BLOOD》 *
KU，BO MI ET AL.: "Acquired resistance to AZD9291 as an upfront treatment is dependent on ERK signaling in a preclinical model", 《PLOS ONE》 *
LIU，XIAOBO ET AL.: "Design， Synthesis and Biological Evaluation of 6，7-Disubstituted-4-phenoxyquinoline Derivatives Bearing Pyridazinone Moiety as c-Met Inhibitors", 《MOLECULES》 *
ROBICHAUD NATHANIEL ET AL.: "Translational control in the tumor microenvironment promotes lung metastasis: Phosphorylation of eIF4E in neutrophils", 《PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA》 *
YAN，S. BETTY ET AL.: "MET-targeting antibody (emibetuzumab) and kinase inhibitor (merestinib) as single agent or in combination in a cancer model bearing MET exon 14 skipping", 《INVESTIGATIONAL NEW DRUGS》 *

Also Published As

Publication number Publication date
JP7443373B2 (ja) 2024-03-05
WO2020048455A1 (zh) 2020-03-12
AU2019335450A1 (en) 2021-05-06
JP2021536503A (ja) 2021-12-27
US20220388983A1 (en) 2022-12-08
EP3848365A1 (en) 2021-07-14
US11952364B2 (en) 2024-04-09
KR20210054548A (ko) 2021-05-13
EP3848365A4 (en) 2022-06-01
CN112739691B (zh) 2023-05-23
CA3111105A1 (en) 2020-03-12
BR112021004003A2 (pt) 2021-05-25

Similar Documents

Publication Publication Date Title
CA2858447C (en) Tryazolopyridine derivatives as kinase inhibitors
CN114364672A (zh) 苯并异噁唑磺酰胺衍生物
US10844015B2 (en) Pyridine dicarboxamide derivatives as bromodomain inhibitors
WO2020216190A1 (zh) 一种喹唑啉化合物及其在医药上的应用
EP3359531B1 (en) 2-oxo-1,2-dihydropyridine-3,5-dicarboxamide compounds as bromodomain inhibitors
CN110896634A (zh) 作为atf4抑制剂用于治疗癌症和其它疾病的2-(4-氯苯氧基)-n-((1-(2-(4-氯苯氧基)乙炔氮杂环丁烷-3-基)甲基)乙酰胺衍生物和相关化合物
TW200951139A (en) Chemical compounds 293
CN111630051B (zh) 作为法尼醇x受体调节剂的烯烃螺环化合物
WO2015144021A1 (zh) 取代氮杂环类衍生物、含其的药物组合物及其在抗肿瘤中的应用
TW201348213A (zh) 喹唑啉二酮衍生物
WO2022088551A1 (zh) 吲唑类衍生物及其制备方法和应用
CN112739691A (zh) 用作抗癌药的trk抑制剂
CN110869352A (zh) 化学化合物
CN113454081A (zh) 咪唑并吡啶基化合物及其用于治疗增生性疾病的用途
CN109384785B (zh) 吡咯并吡啶酮类衍生物、其制备方法及其在医药上的用途
EP3589615B1 (en) Pyridyl derivatives as bromodomain inhibitors
CN115380036A (zh) Sstr5拮抗剂
KR20210057777A (ko) 3-[(1S)-1-이미다조[1,2-a]피리딘-6-일에틸]-5-(1-메틸피라졸-4-일)트리아졸로[4,5-b]피라진 및 이의 다형체의 개선된 제조 방법
JP2024517132A (ja) Ｇｐｒ３５アゴニスト化合物
WO2023137634A1 (zh) 三并环化合物、其制备、药物组合物及应用
CN112384506A (zh) 吲哚啉-1-甲酰胺类化合物、其制备方法及其在医药学上的应用
TW201311681A (zh) 氘代雜環化合物激酶抑制劑

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