MX338150B - Imidazolonilquinolinas [4, 5-c] como inhibidores de proteina cinasa dependiente de adn (adn-pk). - Google Patents

Imidazolonilquinolinas [4, 5-c] como inhibidores de proteina cinasa dependiente de adn (adn-pk).

Info

Publication number
MX338150B
MX338150B MX2013002259A MX2013002259A MX338150B MX 338150 B MX338150 B MX 338150B MX 2013002259 A MX2013002259 A MX 2013002259A MX 2013002259 A MX2013002259 A MX 2013002259A MX 338150 B MX338150 B MX 338150B
Authority
MX
Mexico
Prior art keywords
compounds
formula
quinolines
imidazo
inhibitors
Prior art date
Application number
MX2013002259A
Other languages
English (en)
Other versions
MX2013002259A (es
Inventor
Werner Mederski
Frank Zenke
Thomas Fuchss
Original Assignee
Merck Patent Gmbh
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 Merck Patent Gmbh filed Critical Merck Patent Gmbh
Publication of MX2013002259A publication Critical patent/MX2013002259A/es
Publication of MX338150B publication Critical patent/MX338150B/es

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    • 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
    • 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
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
    • C12Y207/11—Protein-serine/threonine kinases (2.7.11)
    • C12Y207/11001—Non-specific serine/threonine protein kinase (2.7.11.1), i.e. casein kinase or checkpoint kinase

Landscapes

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

Abstract

La invención se refiere a compuestos de las fórmulas (I) y (II) (Ver Formulas) en donde R1, R2, R3, R4, R5, R8, X y m presentan el significado en las reivindicaciones, y/o sus sales, tautómeros y estereoisómeros fisiológicamente inocuos, incluyendo sus mezclas en todas las proporciones. Los compuestos de la fórmula (I) se pueden usar para la inhibición de las serina-treonina-prote ína cinasas, así como para la sensibilización de células cancerosas a los agentes anticáncer y/o radiación ionizante. También es objeto de la invención el uso de los compuestos de la fórmula (I) en la prevención, la terapia o el control del curso de cáncer, tumores, metástasis o trastornos de la angiogénesis, en combinación con radioterapia y/o un agente anticáncer. La invención también se refiere a un proceso para la preparación de los compuestos de la fórmula (I) por reacción de los compuestos de las fórmulas (II) eventualmente conversión de una base o un ácido de los compuestos de la fórmula (I) en una de sus sales.
MX2013002259A 2010-08-28 2011-07-26 Imidazolonilquinolinas [4, 5-c] como inhibidores de proteina cinasa dependiente de adn (adn-pk). MX338150B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102010035744A DE102010035744A1 (de) 2010-08-28 2010-08-28 Imidazolonylchinoline
PCT/EP2011/003744 WO2012028233A1 (de) 2010-08-28 2011-07-26 Imidazo [4,5-c]chinoline als dna-pk-inhibitoren

Publications (2)

Publication Number Publication Date
MX2013002259A MX2013002259A (es) 2013-05-09
MX338150B true MX338150B (es) 2016-04-05

Family

ID=44509164

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2013002259A MX338150B (es) 2010-08-28 2011-07-26 Imidazolonilquinolinas [4, 5-c] como inhibidores de proteina cinasa dependiente de adn (adn-pk).

Country Status (25)

Country Link
US (3) US9000153B2 (es)
EP (1) EP2609082B1 (es)
JP (1) JP5882329B2 (es)
KR (1) KR101912475B1 (es)
CN (1) CN103068803B (es)
AR (1) AR082728A1 (es)
AU (1) AU2011298013B9 (es)
BR (1) BR112013004613B1 (es)
CA (1) CA2809553C (es)
CY (1) CY1116281T1 (es)
DE (1) DE102010035744A1 (es)
DK (1) DK2609082T3 (es)
EA (1) EA022095B1 (es)
ES (1) ES2536313T3 (es)
HK (1) HK1184154A1 (es)
HR (1) HRP20150489T1 (es)
HU (1) HUE025692T2 (es)
IL (1) IL224903A (es)
MX (1) MX338150B (es)
PL (1) PL2609082T3 (es)
PT (1) PT2609082E (es)
RS (1) RS54038B1 (es)
SG (1) SG187954A1 (es)
SI (1) SI2609082T1 (es)
WO (1) WO2012028233A1 (es)

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WO2013163190A1 (en) 2012-04-24 2013-10-31 Vertex Pharmaceutical Incorporated Dna-pk inhibitors
LT2970218T (lt) * 2013-03-12 2019-03-12 Vertex Pharmaceuticals Incorporated Dna-pk inhibitoriai
SG11201602962PA (en) 2013-10-17 2016-05-30 Vertex Pharma Co-crystals of (s)-n-methyl-8-(1-((2'-methyl-[4,5'-bipyrimidin]-6-yl)amino)propan-2-yl)quinoline-4-carboxamide and deuterated derivatives thereof as dna-pk inhibitors
NO2714752T3 (es) 2014-05-08 2018-04-21
EP3560924B1 (de) * 2015-04-02 2021-03-31 Merck Patent GmbH Imidazolonylchinoline und deren verwendung als atm-kinase-inhibitoren
GB201516504D0 (en) 2015-09-17 2015-11-04 Astrazeneca Ab Imadazo(4,5-c)quinolin-2-one Compounds and their use in treating cancer
KR20190062485A (ko) 2016-09-27 2019-06-05 버텍스 파마슈티칼스 인코포레이티드 Dna-손상제 및 dna-pk 저해제의 조합을 사용한 암 치료 방법
US20200101080A1 (en) * 2017-03-31 2020-04-02 Bioventures, Llc Inhibitors of dna pk and uses thereof
JP7224337B2 (ja) 2017-08-11 2023-02-17 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング ３－フルオロ－４－［７－メトキシ－３－メチル－８－（１－メチル－１Ｈ－ピラゾール－４－イル）－２－オキソ－２，３－ジヒドロ－イミダゾ［４，５－ｃ］キノリン－１－イル］－ベンゾニトリル含む医薬製剤
WO2019177971A1 (en) * 2018-03-12 2019-09-19 Mavupharma, Inc. Ectonucleotide pyrophosphatase-phosphodiesterase 1 (enpp-1) inhibitors and uses thereof
AU2019233596A1 (en) * 2018-03-14 2020-10-08 Merck Patent Gmbh Compounds and uses thereof to treat tumors in a subject
TWI820146B (zh) 2018-06-15 2023-11-01 瑞典商阿斯特捷利康公司 嘌呤酮化合物及其在治療癌症中之用途
CN111909144A (zh) * 2019-05-10 2020-11-10 山东轩竹医药科技有限公司 喹唑啉类dna-pk抑制剂
PT3996688T (pt) 2019-07-10 2023-11-29 Merck Patent Gmbh Preparação farmacêutica
US20230014730A1 (en) 2019-09-23 2023-01-19 Nanjing Zhengxiang Pharmaceuticals Co., Ltd. Phosphodiesterase inhibitors and use
IL292613A (en) 2019-11-01 2022-07-01 Ares Trading Sa Combined inhibition of pd-1, tgf-beta and atm along with radiotherapy for cancer treatment
US20230226041A1 (en) 2020-06-18 2023-07-20 Merck Patent Gmbh Compounds for the treatment of viral infections
JP2023539715A (ja) 2020-06-24 2023-09-19 アストラゼネカ ユーケー リミテッド 抗体－薬物コンジュゲートとａｔｍ阻害剤との組合わせ

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Also Published As

Publication number Publication date
ES2536313T3 (es) 2015-05-22
HRP20150489T1 (hr) 2015-06-05
DE102010035744A1 (de) 2012-03-01
PT2609082E (pt) 2015-06-05
CA2809553A1 (en) 2012-03-08
BR112013004613B1 (pt) 2021-08-03
AU2011298013B9 (en) 2015-08-20
IL224903A (en) 2016-02-29
SI2609082T1 (sl) 2015-06-30
PL2609082T3 (pl) 2015-07-31
AU2011298013A1 (en) 2013-04-11
US9598408B2 (en) 2017-03-21
CN103068803A (zh) 2013-04-24
CA2809553C (en) 2019-02-26
EP2609082B1 (de) 2015-02-18
JP5882329B2 (ja) 2016-03-09
KR20130106367A (ko) 2013-09-27
EP2609082A1 (de) 2013-07-03
CY1116281T1 (el) 2017-02-08
WO2012028233A1 (de) 2012-03-08
KR101912475B1 (ko) 2018-10-26
CN103068803B (zh) 2016-01-20
HK1184154A1 (zh) 2014-01-17
MX2013002259A (es) 2013-05-09
US9000153B2 (en) 2015-04-07
HUE025692T2 (en) 2016-04-28
AU2011298013B2 (en) 2015-01-29
US20150203491A1 (en) 2015-07-23
US20130172337A1 (en) 2013-07-04
US20170166567A1 (en) 2017-06-15
EA022095B1 (ru) 2015-10-30
SG187954A1 (en) 2013-04-30
RS54038B1 (en) 2015-10-30
DK2609082T3 (en) 2015-05-11
EA201300288A1 (ru) 2013-08-30
AR082728A1 (es) 2012-12-26
JP2013536256A (ja) 2013-09-19
BR112013004613A2 (pt) 2017-04-04

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