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CN108026053A8 - 作为mIDH1抑制剂的稠合的咪唑类化合物 - Google Patents

作为mIDH1抑制剂的稠合的咪唑类化合物 Download PDF

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Publication number
CN108026053A8
CN108026053A8 CN201680054868.7A CN201680054868A CN108026053A8 CN 108026053 A8 CN108026053 A8 CN 108026053A8 CN 201680054868 A CN201680054868 A CN 201680054868A CN 108026053 A8 CN108026053 A8 CN 108026053A8
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CN
China
Prior art keywords
compounds
condensed
glyoxaline compound
midh1
inhibitor
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
CN201680054868.7A
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English (en)
Other versions
CN108026053B (zh
CN108026053A (zh
Inventor
O.潘克宁
I.哈通
H.雷温克尔
D.阮
L.佐恩
P.黑尔弗里希
K.齐默曼
R.诺伊豪斯
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.)
Deutsches Krebsforschungszentrum DKFZ
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Bayer Pharma AG
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Publication date
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Publication of CN108026053A publication Critical patent/CN108026053A/zh
Publication of CN108026053A8 publication Critical patent/CN108026053A8/zh
Application granted granted Critical
Publication of CN108026053B publication Critical patent/CN108026053B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/30—Nitrogen atoms not forming part of a nitro radical
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/437—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 containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • 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
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/10—Nitrogen as only ring hetero atom

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

本发明涉及通式(I)的化合物：其中 R1、R2、R3、R4、R6、R7、R8、R9、R10、R11、R12、R13和X如本文中所定义，涉及制备所述化合物的方法，可用于制备所述化合物的中间体化合物，包含所述化合物的药物组合物及组合产品和所述化合物作为单独药剂或与其它活性成分组合用于制备用于治疗或预防疾病(特别是赘生物)的药物组合物的用途。
CN201680054868.7A 2015-07-21 2016-07-14 作为mIDH1抑制剂的稠合的咪唑类化合物 Expired - Fee Related CN108026053B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP15177743.0A EP3121166A1 (en) 2015-07-21 2015-07-21 Fused imidazoles as midh1 inhibitors
EP15177743.0 2015-07-21
PCT/EP2016/066720 WO2017012967A1 (en) 2015-07-21 2016-07-14 Fused imidazoles as midh1 inhibitors

Publications (3)

Publication Number Publication Date
CN108026053A CN108026053A (zh) 2018-05-11
CN108026053A8 true CN108026053A8 (zh) 2018-08-03
CN108026053B CN108026053B (zh) 2021-10-08

Family

ID=53719697

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201680054868.7A Expired - Fee Related CN108026053B (zh) 2015-07-21 2016-07-14 作为mIDH1抑制剂的稠合的咪唑类化合物

Country Status (6)

Country Link
US (1) US10919862B2 (zh)
EP (2) EP3121166A1 (zh)
JP (1) JP6830948B2 (zh)
CN (1) CN108026053B (zh)
CA (1) CA2992960A1 (zh)
WO (1) WO2017012967A1 (zh)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CU24410B1 (es) 2014-02-11 2019-05-03 Bayer Pharma AG Benzimidazol-2-aminas como inhibidores de midh1
HK1226398A1 (zh) 2014-02-11 2017-09-29 拜耳医药股份公司 作为midh1抑制剂的苯并咪唑-2-胺
EP3209660B1 (en) 2014-10-23 2020-06-17 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts 1-cyclohexyl-2-phenylaminobenzimidazoles as midh1 inhibitors for the treatment of tumors
CN107810176B (zh) 2015-06-08 2020-10-16 德国癌症研究公共权益基金会 作为mIDH1抑制剂的N-薄荷基苯并咪唑类化合物
CN107949557B (zh) 2015-07-07 2021-11-02 德国癌症研究公共权益基金会 作为mIDH1抑制剂的2-芳基-和2-芳烷基-苯并咪唑类
JP6824954B2 (ja) 2015-07-16 2021-02-03 ドイチェス クレープスフォルシュングスツェントルム シュティフトゥング デス エッフェントリッヒェン レヒツ ｍＩＤＨ１阻害剤としての５−ヒドロキシアルキルベンズイミダゾール
TW201718513A (zh) 2015-07-27 2017-06-01 拜耳製藥公司 製備經取代之３－（２－苯胺－１－環己基－１ｈ－苯并咪唑－５－基）丙酸衍生物之方法
TW201708193A (zh) 2015-07-27 2017-03-01 拜耳製藥公司 突變之異檸檬酸脫氫酶ｉｄｈ１ ｒ１３２ｈ之抑制劑
TWI794171B (zh) 2016-05-11 2023-03-01 美商滬亞生物國際有限公司 Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療
TWI808055B (zh) 2016-05-11 2023-07-11 美商滬亞生物國際有限公司 Hdac 抑制劑與 pd-1 抑制劑之組合治療
WO2018228476A1 (zh) * 2017-06-15 2018-12-20 南京明德新药研发股份有限公司 苯并咪唑类化合物及其应用
WO2019015672A1 (zh) * 2017-07-21 2019-01-24 南京明德新药研发股份有限公司 吡啶并咪唑类化合物及其应用
EP3661559A1 (en) 2017-08-01 2020-06-10 Deutsches Krebsforschungszentrum Stiftung des Öffentlichen Rechts Combination of midh1 inhibitors and dna hypomethylating agents (hma)
EP3816158B1 (en) 2018-06-26 2023-10-25 KPC Pharmaceuticals, Inc. Benzimidazole derivatives and use thereof as idh1 inhibitors
TWI760017B (zh) * 2019-12-23 2022-04-01 大陸商昆藥集團股份有限公司 一種ｉｄｈ１突變體抑制劑的鹽型、晶型及其製備方法

Family Cites Families (15)

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Publication number Priority date Publication date Assignee Title
US7531553B2 (en) * 2003-03-21 2009-05-12 Amgen Inc. Heterocyclic compounds and methods of use
EP1910358A2 (en) * 2005-07-14 2008-04-16 Astellas Pharma Inc. Heterocyclic janus kinase 3 inhibitors
WO2008153701A1 (en) * 2007-05-24 2008-12-18 Schering Corporation Compounds for inhibiting ksp kinesin activity
AU2010223919B2 (en) * 2009-03-13 2016-03-31 Les Laboratoires Servier Methods and compositions for cell-proliferation-related disorders
CN102827170A (zh) * 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
US10445772B1 (en) 2011-09-09 2019-10-15 Google Llc Label placement based on objects in photographic images
CU24410B1 (es) 2014-02-11 2019-05-03 Bayer Pharma AG Benzimidazol-2-aminas como inhibidores de midh1
HK1226398A1 (zh) 2014-02-11 2017-09-29 拜耳医药股份公司 作为midh1抑制剂的苯并咪唑-2-胺
CN107108522B (zh) 2014-10-23 2020-12-01 德国癌症研究中心 作为mIDH1抑制剂的苯并咪唑-2-胺
EP3209660B1 (en) 2014-10-23 2020-06-17 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts 1-cyclohexyl-2-phenylaminobenzimidazoles as midh1 inhibitors for the treatment of tumors
CN107810176B (zh) 2015-06-08 2020-10-16 德国癌症研究公共权益基金会 作为mIDH1抑制剂的N-薄荷基苯并咪唑类化合物
CN107949557B (zh) 2015-07-07 2021-11-02 德国癌症研究公共权益基金会 作为mIDH1抑制剂的2-芳基-和2-芳烷基-苯并咪唑类
JP6824954B2 (ja) 2015-07-16 2021-02-03 ドイチェス クレープスフォルシュングスツェントルム シュティフトゥング デス エッフェントリッヒェン レヒツ ｍＩＤＨ１阻害剤としての５−ヒドロキシアルキルベンズイミダゾール
TW201708193A (zh) 2015-07-27 2017-03-01 拜耳製藥公司 突變之異檸檬酸脫氫酶ｉｄｈ１ ｒ１３２ｈ之抑制劑
TW201718513A (zh) 2015-07-27 2017-06-01 拜耳製藥公司 製備經取代之３－（２－苯胺－１－環己基－１ｈ－苯并咪唑－５－基）丙酸衍生物之方法

Also Published As

Publication number Publication date
CN108026053B (zh) 2021-10-08
EP3121166A1 (en) 2017-01-25
JP2018524383A (ja) 2018-08-30
EP3325451A1 (en) 2018-05-30
EP3325451B1 (en) 2019-07-10
US20180215717A1 (en) 2018-08-02
WO2017012967A1 (en) 2017-01-26
CA2992960A1 (en) 2017-01-26
JP6830948B2 (ja) 2021-02-17
US10919862B2 (en) 2021-02-16
CN108026053A (zh) 2018-05-11

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CI02 Correction of invention patent application
CI02 Correction of invention patent application

Correction item: Biological Conservation Information

Correct: Have

Number: 19-02

Page: The title page

Volume: 34

Correction item: Biological Conservation Information

Correct: Have

Number: 19-02

Volume: 34

TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20200511

Address after: Heidelberg, Germany

Applicant after: DEUTSCHES KREBSFORSCHUNGSZENTRUM STIFTUNG DES OFFENTLICHEN RECHTS

Address before: Berlin

Applicant before: BAYER PHARMA AG

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CF01 Termination of patent right due to non-payment of annual fee
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Granted publication date: 20211008