WO2018157737A1 - Inhibiteur de kinase multi-cibles - Google Patents

Inhibiteur de kinase multi-cibles Download PDF

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Publication number
WO2018157737A1
WO2018157737A1 PCT/CN2018/076447 CN2018076447W WO2018157737A1 WO 2018157737 A1 WO2018157737 A1 WO 2018157737A1 CN 2018076447 W CN2018076447 W CN 2018076447W WO 2018157737 A1 WO2018157737 A1 WO 2018157737A1
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WO
WIPO (PCT)
Prior art keywords
fluorophenyl
compound
formula
structural formula
cyclopropane
Prior art date
Application number
PCT/CN2018/076447
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English (en)
Chinese (zh)
Inventor
金锋
冯贻东
王彦青
佘琴
靳如意
唐田
冯汉林
于琳
Original Assignee
深圳海王医药科技研究院有限公司
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Publication of WO2018157737A1 publication Critical patent/WO2018157737A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed 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
    • A61K31/435—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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
    • 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
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic 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
    • A61K31/435—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
    • A61K31/506—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (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)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

La présente invention concerne un inhibiteur de protéine kinase multi-cibles, une composition pharmaceutique de celui-ci, et une utilisation de l'inhibiteur de kinase multi-cibles dans la préparation d'un médicament pour le traitement de maladies induites par une activité de protéine kinase anormale. L'inhibiteur de kinase multi-cibles de la présente invention est représenté par la formule structurale générale (I). L'inhibiteur de kinase multi-cibles de la présente invention possède un effet inhibiteur idéal et une sélectivité spécifique, et présente une large perspective dans le traitement de maladies hétérogènes complexes et de permet de surmonter la résistance aux médicaments.
PCT/CN2018/076447 2017-03-02 2018-02-12 Inhibiteur de kinase multi-cibles WO2018157737A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201710121054.7A CN108530464B (zh) 2017-03-02 2017-03-02 一种多靶点激酶抑制剂
CN201710121054.7 2017-03-02

Publications (1)

Publication Number Publication Date
WO2018157737A1 true WO2018157737A1 (fr) 2018-09-07

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ID=63369757

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/076447 WO2018157737A1 (fr) 2017-03-02 2018-02-12 Inhibiteur de kinase multi-cibles

Country Status (2)

Country Link
CN (1) CN108530464B (fr)
WO (1) WO2018157737A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109384799A (zh) * 2018-11-12 2019-02-26 深圳海王医药科技研究院有限公司 一种多靶点激酶抑制剂化合物的晶型a及制备方法和含有其的药物组合物
EP4108666A4 (fr) * 2020-02-18 2024-03-13 Shenzhen Neptunus Pharmaceutical Res Institute Co Ltd Inhibiteur de la tyrosine kinase à plusieurs cibles

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021180006A1 (fr) * 2020-03-10 2021-09-16 南京明德新药研发有限公司 Composés de pyridine à substitution vinylique
CN114644642B (zh) * 2022-04-06 2023-05-12 深圳海王医药科技研究院有限公司 一种噻吩并吡啶化合物的晶型a、制备方法及其药物组合物

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009026720A1 (fr) * 2007-08-29 2009-03-05 Methylgene Inc. Procédés et intermédiaires de préparation d'inhibiteurs de kinases hétérocycliques fusionnés
CN101796055A (zh) * 2005-05-20 2010-08-04 梅赛尔基因股份有限公司 Vegf受体和hgf受体信号的抑制剂
CN102086211A (zh) * 2009-12-08 2011-06-08 深圳市东阳光实业发展有限公司 作为蛋白激酶抑制剂的芳杂环化合物
CN102256493A (zh) * 2008-10-29 2011-11-23 迪赛孚尔制药有限公司 表现出抗癌活性和抗增殖活性的环丙烷酰胺及其类似物
CN102827186A (zh) * 2011-06-16 2012-12-19 中国科学院上海药物研究所 一类吡啶并五元杂环衍生物及其制备方法和用途
CN102947315A (zh) * 2010-04-16 2013-02-27 梅特希尔基因公司 蛋白酪氨酸激酶活性抑制剂
CN105777776A (zh) * 2007-08-29 2016-07-20 梅特希尔基因公司 蛋白酪氨酸激酶活性的抑制剂

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101796055A (zh) * 2005-05-20 2010-08-04 梅赛尔基因股份有限公司 Vegf受体和hgf受体信号的抑制剂
WO2009026720A1 (fr) * 2007-08-29 2009-03-05 Methylgene Inc. Procédés et intermédiaires de préparation d'inhibiteurs de kinases hétérocycliques fusionnés
CN105777776A (zh) * 2007-08-29 2016-07-20 梅特希尔基因公司 蛋白酪氨酸激酶活性的抑制剂
CN102256493A (zh) * 2008-10-29 2011-11-23 迪赛孚尔制药有限公司 表现出抗癌活性和抗增殖活性的环丙烷酰胺及其类似物
CN102086211A (zh) * 2009-12-08 2011-06-08 深圳市东阳光实业发展有限公司 作为蛋白激酶抑制剂的芳杂环化合物
CN102947315A (zh) * 2010-04-16 2013-02-27 梅特希尔基因公司 蛋白酪氨酸激酶活性抑制剂
CN102827186A (zh) * 2011-06-16 2012-12-19 中国科学院上海药物研究所 一类吡啶并五元杂环衍生物及其制备方法和用途

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109384799A (zh) * 2018-11-12 2019-02-26 深圳海王医药科技研究院有限公司 一种多靶点激酶抑制剂化合物的晶型a及制备方法和含有其的药物组合物
EP4108666A4 (fr) * 2020-02-18 2024-03-13 Shenzhen Neptunus Pharmaceutical Res Institute Co Ltd Inhibiteur de la tyrosine kinase à plusieurs cibles

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CN108530464B (zh) 2020-10-27
CN108530464A (zh) 2018-09-14

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