WO2019157879A1 - Composé hétérocyclique agissant en tant qu'inhibiteur de trk - Google Patents

Composé hétérocyclique agissant en tant qu'inhibiteur de trk Download PDF

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Publication number
WO2019157879A1
WO2019157879A1 PCT/CN2019/000040 CN2019000040W WO2019157879A1 WO 2019157879 A1 WO2019157879 A1 WO 2019157879A1 CN 2019000040 W CN2019000040 W CN 2019000040W WO 2019157879 A1 WO2019157879 A1 WO 2019157879A1
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WO
WIPO (PCT)
Prior art keywords
group
alkyl
halogen
hydrogen
optionally substituted
Prior art date
Application number
PCT/CN2019/000040
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English (en)
Chinese (zh)
Inventor
孔祥龙
周超
郑之祥
Original Assignee
北京诺诚健华医药科技有限公司
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
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Application filed by 北京诺诚健华医药科技有限公司 filed Critical 北京诺诚健华医药科技有限公司
Publication of WO2019157879A1 publication Critical patent/WO2019157879A1/fr

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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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)

Abstract

La présente invention concerne un composé, une composition pharmaceutique contenant le composé, un procédé de préparation du composé, et une utilisation du composé en tant qu'inhibiteur de TRK. Le composé est le composé tel que présenté dans la formule (I), ou un sel pharmaceutiquement acceptable, un promédicament, un composé solvant, un polymorphe, un isomère ou un dérivé isotopique stable de celui-ci. La présente invention concerne également une utilisation du composé dans le traitement ou la prévention de maladies associées à TRK, telles que des tumeurs, et un procédé d'application du composé pour traiter lesdites maladies.
PCT/CN2019/000040 2018-02-13 2019-03-04 Composé hétérocyclique agissant en tant qu'inhibiteur de trk WO2019157879A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201810150011.6A CN110156813B (zh) 2018-02-13 2018-02-13 作为trk抑制剂的杂环化合物
CN201810150011.6 2018-02-13

Publications (1)

Publication Number Publication Date
WO2019157879A1 true WO2019157879A1 (fr) 2019-08-22

Family

ID=67619767

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/000040 WO2019157879A1 (fr) 2018-02-13 2019-03-04 Composé hétérocyclique agissant en tant qu'inhibiteur de trk

Country Status (2)

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CN (1) CN110156813B (fr)
WO (1) WO2019157879A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3770161A4 (fr) * 2018-04-16 2021-04-28 Shenzhen TargetRx, Inc. Composé macrocyclique di(hétéro)aryle pour inhiber l'activité de la protéine kinase
CN113582994A (zh) * 2021-09-28 2021-11-02 北京鑫开元医药科技有限公司 具有trk激酶抑制活性的化合物、制备方法、组合物及其用途
CN115772170A (zh) * 2021-12-03 2023-03-10 徐诺药业(南京)有限公司 一种吡唑并[1,5-a]吡啶衍生物及其制备方法和应用
US11878987B2 (en) 2018-06-25 2024-01-23 Beijing Innocare Pharma Tech Co., Ltd. Heterocyclic compound as TRK inhibitor

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111171049B (zh) * 2018-11-09 2021-06-04 山东轩竹医药科技有限公司 酪氨酸激酶抑制剂及其用途
CN113773335A (zh) * 2019-06-21 2021-12-10 成都海博为药业有限公司 一种作为蛋白质激酶抑制剂的化合物及其制备方法和用途
WO2021042890A1 (fr) * 2019-09-04 2021-03-11 罗欣药业(上海)有限公司 Composé hétérocyclique et son application en tant qu'inhibiteur de trk kinase
CN114437075A (zh) * 2020-11-03 2022-05-06 上海瑶琪生物科技有限公司 用作ntrk激酶抑制剂的化合物及其应用
CN113444070A (zh) * 2021-07-28 2021-09-28 深圳市真味生物科技有限公司 一种由手性叔丁基亚磺酰胺合成手性尼古丁的制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1780840A (zh) * 2003-02-28 2006-05-31 帝人制药株式会社 吡唑并[1,5－a]嘧啶衍生物
CN102971322A (zh) * 2010-05-20 2013-03-13 阵列生物制药公司 作为trk激酶抑制剂的大环化合物
CN106008523A (zh) * 2009-07-09 2016-10-12 阵列生物制药公司 作为TRK激酶抑制剂的被取代的吡唑并[1,5-a]嘧啶化合物
CN106232597A (zh) * 2013-12-10 2016-12-14 建新公司 原肌球蛋白相关激酶(trk)抑制剂
CN107231803A (zh) * 2014-12-18 2017-10-03 建新公司 原肌球蛋白相关激酶(trk)抑制剂的药物制剂

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA031863B1 (ru) * 2014-01-24 2019-03-29 ТиПи ТЕРАПЬЮТИКС, ИНК. Диарильные макроциклы в качестве модуляторов протеинкиназ
TW201927790A (zh) * 2017-11-10 2019-07-16 美商安捷克斯製藥公司 作為trk激酶抑制劑之巨環化合物及其用途
WO2019149131A1 (fr) * 2018-01-30 2019-08-08 上海吉倍生物技术有限公司 Composé ayant une structure moléculaire macrocyclique et son utilisation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1780840A (zh) * 2003-02-28 2006-05-31 帝人制药株式会社 吡唑并[1,5－a]嘧啶衍生物
CN106008523A (zh) * 2009-07-09 2016-10-12 阵列生物制药公司 作为TRK激酶抑制剂的被取代的吡唑并[1,5-a]嘧啶化合物
CN102971322A (zh) * 2010-05-20 2013-03-13 阵列生物制药公司 作为trk激酶抑制剂的大环化合物
CN106232597A (zh) * 2013-12-10 2016-12-14 建新公司 原肌球蛋白相关激酶(trk)抑制剂
CN107231803A (zh) * 2014-12-18 2017-10-03 建新公司 原肌球蛋白相关激酶(trk)抑制剂的药物制剂

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3770161A4 (fr) * 2018-04-16 2021-04-28 Shenzhen TargetRx, Inc. Composé macrocyclique di(hétéro)aryle pour inhiber l'activité de la protéine kinase
US11358973B2 (en) 2018-04-16 2022-06-14 Shenzhen Targetrx, Inc. Di(hetero)aryl macrocyclic compound for inhibiting protein kinase activity
US11878987B2 (en) 2018-06-25 2024-01-23 Beijing Innocare Pharma Tech Co., Ltd. Heterocyclic compound as TRK inhibitor
CN113582994A (zh) * 2021-09-28 2021-11-02 北京鑫开元医药科技有限公司 具有trk激酶抑制活性的化合物、制备方法、组合物及其用途
CN113582994B (zh) * 2021-09-28 2022-02-11 北京鑫开元医药科技有限公司 具有trk激酶抑制活性的化合物、制备方法、组合物及其用途
CN115772170A (zh) * 2021-12-03 2023-03-10 徐诺药业(南京)有限公司 一种吡唑并[1,5-a]吡啶衍生物及其制备方法和应用

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CN110156813A (zh) 2019-08-23
CN110156813B (zh) 2023-07-25

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