CN116940565A - 作为nuak激酶的抑制剂的异吲哚啉酮氨基嘧啶化合物、其组合物和用途 - Google Patents

作为nuak激酶的抑制剂的异吲哚啉酮氨基嘧啶化合物、其组合物和用途 Download PDF

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Publication number
CN116940565A
CN116940565A CN202280019578.4A CN202280019578A CN116940565A CN 116940565 A CN116940565 A CN 116940565A CN 202280019578 A CN202280019578 A CN 202280019578A CN 116940565 A CN116940565 A CN 116940565A
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China
Prior art keywords
alkyl
alkylene
heterocycloalkyl
haloalkyl
halogen
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Pending
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CN202280019578.4A
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English (en)
Chinese (zh)
Inventor
R·阿尔-阿瓦尔
L·阿蒂萨诺
M·艾萨克
Y·刘
D·斯米尔
D·尤林
J·弗拉纳
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.)
Ontario Cancer Institute
University of Toronto
Mt Sinai Hospital
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Ontario Cancer Institute
University of Toronto
Mt Sinai Hospital
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Publication of CN116940565A publication Critical patent/CN116940565A/zh
Pending legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • 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
    • 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
    • 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
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • 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
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • 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
    • 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
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
CN202280019578.4A 2021-01-07 2022-01-07 作为nuak激酶的抑制剂的异吲哚啉酮氨基嘧啶化合物、其组合物和用途 Pending CN116940565A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202163134747P 2021-01-07 2021-01-07
US63/134,747 2021-01-07
PCT/CA2022/050016 WO2022147622A1 (en) 2021-01-07 2022-01-07 Isoindolinone aminopyrimidine compounds as inhibitors of nuak kinases, compositions and uses thereof

Publications (1)

Publication Number Publication Date
CN116940565A true CN116940565A (zh) 2023-10-24

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ID=82357069

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CN202280019578.4A Pending CN116940565A (zh) 2021-01-07 2022-01-07 作为nuak激酶的抑制剂的异吲哚啉酮氨基嘧啶化合物、其组合物和用途

Country Status (7)

Country Link
US (1) US20240092763A1 (https=)
EP (1) EP4277902A4 (https=)
JP (1) JP2024502175A (https=)
CN (1) CN116940565A (https=)
AU (1) AU2022206470A1 (https=)
CA (1) CA3204401A1 (https=)
WO (1) WO2022147622A1 (https=)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102939283B1 (ko) * 2022-05-03 2026-03-13 한국화학연구원 5-클로로-2,4-다이아미노피리미딘을 포함하는 키나아제 억제 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물
US20260085036A1 (en) * 2022-09-12 2026-03-26 Mihkal Gmbh Novel nootropic prodrugs of henethylamine
KR20240156074A (ko) * 2023-04-21 2024-10-29 (주)엠디바이오팜 Hpk1 및 mlk3 저해제 및 이를 함유하는 항암용 조성물
CN116947764B9 (zh) * 2023-07-13 2025-07-25 特科罗生物科技(成都)有限公司 一种嘧啶胺类nuak抑制剂及其制备方法和用途
KR20250041906A (ko) * 2023-09-19 2025-03-26 (주)엠디바이오팜 Hpk1 및 mlk3 저해 활성을 갖는 신규한 화합물 및 이를 함유하는 항암용 조성물

Citations (4)

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CN101044137A (zh) * 2004-08-20 2007-09-26 贝林格尔·英格海姆国际有限公司 作为plk抑制剂的2,4－二（氨基苯基）嘧啶
WO2010090875A1 (en) * 2009-01-21 2010-08-12 Rigel Pharmaceuticals, Inc. Derivatives of n2-(3-pyridil or phenyl)-n4-(4-piperidyl)-2,4-pyrimidinediamine useful in the treatment of inflammatory, autoimmune or proliferative diseases
CN103153064A (zh) * 2010-10-14 2013-06-12 阿里亚德医药股份有限公司 抑制egfr导致的癌症中细胞增殖的方法
CN110214138A (zh) * 2017-01-26 2019-09-06 韩美药品株式会社 嘧啶化合物及其药物用途

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PT1660458E (pt) * 2003-08-15 2012-04-27 Novartis Ag 2,4-pirimidinodiaminas úteis no tratamento de doenças neoplásicas, desordens inflamatórias e do sistema imunitário
GB0419161D0 (en) * 2004-08-27 2004-09-29 Novartis Ag Organic compounds
CA2634646C (en) * 2005-12-21 2012-04-10 Pfizer Products Inc. Pyrimidine derivatives for the treatment of abnormal cell growth
ES2555803T3 (es) * 2006-10-23 2016-01-08 Cephalon, Inc. Fusión de derivados bicíclicos 2,4-diaminopirimidina como utilizar inhibidores ALK y c-Met
HUE030912T2 (en) * 2008-02-15 2017-06-28 Rigel Pharmaceuticals Inc Pyrimidine-2-amine compounds and their use as inhibitors of yak kinases
MX353308B (es) * 2008-05-21 2018-01-08 Ariad Pharma Inc Derivados fosforosos como inhibidores de cinasa.
PH12012501556A1 (en) * 2009-12-30 2012-10-22 Arqule Inc Substituted naphthalenyl-pyrimidine compounds
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WO2021239133A1 (zh) * 2020-05-29 2021-12-02 南京正大天晴制药有限公司 作为axl抑制剂的嘧啶类化合物

Patent Citations (4)

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CN101044137A (zh) * 2004-08-20 2007-09-26 贝林格尔·英格海姆国际有限公司 作为plk抑制剂的2,4－二（氨基苯基）嘧啶
WO2010090875A1 (en) * 2009-01-21 2010-08-12 Rigel Pharmaceuticals, Inc. Derivatives of n2-(3-pyridil or phenyl)-n4-(4-piperidyl)-2,4-pyrimidinediamine useful in the treatment of inflammatory, autoimmune or proliferative diseases
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EP4277902A1 (en) 2023-11-22
WO2022147622A1 (en) 2022-07-14
EP4277902A4 (en) 2024-12-18
AU2022206470A9 (en) 2024-09-26
US20240092763A1 (en) 2024-03-21
CA3204401A1 (en) 2022-07-14
AU2022206470A1 (en) 2023-07-27
JP2024502175A (ja) 2024-01-17

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