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DE60243587C5 - Arylharnstoff-Verbindungen in Kombination mit anderen zytostatisch oder zytotoxisch wirksamen Stoffen zur Behandlungen menschlicher Krebserkrankungen - Google Patents

Arylharnstoff-Verbindungen in Kombination mit anderen zytostatisch oder zytotoxisch wirksamen Stoffen zur Behandlungen menschlicher Krebserkrankungen Download PDF

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Publication number
DE60243587C5
DE60243587C5 DE60243587.0A DE60243587A DE60243587C5 DE 60243587 C5 DE60243587 C5 DE 60243587C5 DE 60243587 A DE60243587 A DE 60243587A DE 60243587 C5 DE60243587 C5 DE 60243587C5
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DE
Germany
Prior art keywords
use according
administered
urea compound
aryl urea
phenyl
Prior art date
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Expired - Lifetime
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DE60243587.0A
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English (en)
Inventor
Christopher A. Carter
Neil Gibson
Barbara Hibner
Rachel W. Humphrey
Pamela Trail
Patrick Vincent
Yifan Zhai
Jaques Dumas
Bernd Riedl
Uday Khire
Timothy B. Lowinger
William J. Scott
Roger A. Smith
Jill E. Wood
Mary-Katherine Monahan
Reina Natero
Joel Renick
Robert N. Sibley
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Bayer Healthcare LLC
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Bayer Healthcare LLC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • 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
    • 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
    • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
    • 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
    • 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
    • A61K31/495—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
    • 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
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • 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
    • A61K31/65—Tetracyclines
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • 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
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)

Abstract

Verwendung von einer Arylharnstoff-Verbindung und 5-Fluoruracil oder eines pharmazeutisch akzeptablen Salzes davon zur Herstellung eines Medikaments zur Behandlung von einem Krebs, wobei die Arylharnstoff-Verbindung ein Tosylatsalz von N-(4-Chlor-3-(trifluormethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)harnstoff ist.

Description

  • Der X. Zivilsenat des Bundesgerichtshofs hat auf die mündliche Verhandlung vom 10. Oktober 2023
    für Recht erkannt:
    • Auf die Berufung der Beklagten wird das Urteil des 3. Senats (Nichtigkeitssenats) des Bundespatentgerichts vom 29. September 2021 abgeändert.
    • Das europäische Patent 2 305 255 wird mit Wirkung für die Bundesrepublik Deutschland dadurch teilweise für nichtig erklärt, dass Patentanspruch 12 am Ende um folgende Wörter ergänzt wird:
      • „in an oral dosage form“.
      • Im Übrigen wird die Klage abgewiesen.

Claims (12)

  1. Verwendung von einer Arylharnstoff-Verbindung und 5-Fluoruracil oder eines pharmazeutisch akzeptablen Salzes davon zur Herstellung eines Medikaments zur Behandlung von einem Krebs, wobei die Arylharnstoff-Verbindung ein Tosylatsalz von N-(4-Chlor-3-(trifluormethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)harnstoff ist.
  2. Verwendung nach Anspruch 1, wobei der Krebs durch raf-Kinase vermittelt wird.
  3. Verwendung nach Anspruch 1, wobei der Krebs Kolon-, Magen-, Lungen-, Pankreas-, Ovarial-, Prostatakrebs, Leukämie, Melanom, Leberzell-, Nierenkrebs, Glioma, Brust- oder Kopf- und Halskrebs ist.
  4. Verwendung nach Anspruch 1, wobei das Medikament in einer therapeutisch wirksamen Menge an einen Patienten, der es benötigt, durch orale Abgabe oder mittels intravenöser Injektion oder Infusion verabreicht wird.
  5. Verwendung nach Anspruch 1, wobei das Medikament in einer therapeutisch wirksamen Menge an einen Patienten, der es benötigt, in der Form einer Tablette, einer Flüssigkeit, eines topischen Gels, eines Inhalators oder in der Form einer Zusammensetzung mit verzögerter Freisetzung verabreicht wird.
  6. Verwendung nach Anspruch 1, wobei das Tosylatsalz von N-(4-Chlor-3-(trifluormethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)harnstoff an einen Patienten mit einer oralen intravenösen, intramuskulären, subkutanen oder parenteralen Dosierung, die zwischen etwa 0,1 bis etwa 300 mg/kg des Gesamtkörpergewichts variieren kann, verabreicht wird.
  7. Verwendung nach Anspruch 1 zur Inhibierung der Proliferation von Krebszellen in einem Patienten.
  8. Verwendung nach Anspruch 1, wobei die Arylharnstoff-Verbindung gleichzeitig mit 5-Fluoruracil oder einem pharmazeutisch akzeptablen Salz davon verabreicht wird.
  9. Verwendung nach Anspruch 8, wobei die Arylharnstoff-Verbindung und 5-Fluoruracil oder ein pharmazeutisch akzeptables Salz davon in der gleichen Formulierung oder in separaten Formulierungen verabreicht wird.
  10. Verwendung nach Anspruch 1, wobei die Arylharnstoff-Verbindung sequenziell mit 5-Fluoruracil oder einem pharmazeutisch akzeptablen Salz davon in beliebiger Reihenfolge verabreicht wird.
  11. Verwendung nach Anspruch 1, wobei die Arylharnstoff-Verbindung als Tandem mit 5-Fluoruracil oder einem pharmazeutisch akzeptablen Salz davon verabreicht wird, wobei die Arylharnstoff-Verbindung einem Patienten einmal oder mehrmals täglich für bis zu 28 aufeinanderfolgende Tage mit konkurrierender oder intermittierender Verabreichung von 5-Fluoruracil oder einem pharmazeutisch akzeptablen Salz davon über die gleiche Gesamtdauer verabreicht werden kann.
  12. Arylharnstoff-Verbindung, die ein Tosylatsalz von N-(4-Chlor-3-(trifluormethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)harnstoff ist.
DE60243587.0A 2001-12-03 2002-12-03 Arylharnstoff-Verbindungen in Kombination mit anderen zytostatisch oder zytotoxisch wirksamen Stoffen zur Behandlungen menschlicher Krebserkrankungen Expired - Lifetime DE60243587C5 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US33460901P 2001-12-03 2001-12-03
US334609P 2001-12-03
EP10183659A EP2305255B1 (de) 2001-12-03 2002-12-03 Arylharnstoff-Verbindungen in Kombination mit anderen zytostatisch oder zytotoxisch wirksamen Stoffen zur Behandlungen menschlicher Krebserkrankungen

Publications (1)

Publication Number Publication Date
DE60243587C5 true DE60243587C5 (de) 2024-04-18

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ID=23307982

Family Applications (2)

Application Number Title Priority Date Filing Date
DE60243587.0A Expired - Lifetime DE60243587C5 (de) 2001-12-03 2002-12-03 Arylharnstoff-Verbindungen in Kombination mit anderen zytostatisch oder zytotoxisch wirksamen Stoffen zur Behandlungen menschlicher Krebserkrankungen
DE60216139.8T Expired - Lifetime DE60216139T3 (de) 2001-12-03 2002-12-03 Arylharnstoff-verbindungen in kombination mit anderen zytostatisch oder zytotoxisch wirksamen stoffen zur behandlungen menschlicher krebserkrankungen

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DE60216139.8T Expired - Lifetime DE60216139T3 (de) 2001-12-03 2002-12-03 Arylharnstoff-verbindungen in kombination mit anderen zytostatisch oder zytotoxisch wirksamen stoffen zur behandlungen menschlicher krebserkrankungen

Country Status (20)

Country Link
US (4) US20030232765A1 (de)
EP (5) EP2295057B1 (de)
JP (1) JP4982685B2 (de)
AT (1) ATE345130T1 (de)
AU (1) AU2002351196A1 (de)
CA (1) CA2468463C (de)
CY (2) CY1107440T1 (de)
DE (2) DE60243587C5 (de)
DK (2) DK1450799T5 (de)
EC (2) ECSP045178A (de)
ES (5) ES2275931T5 (de)
ME (1) MEP36208A (de)
MX (1) MXPA04005137A (de)
NI (1) NI200400014A (de)
PT (2) PT2305255E (de)
RS (1) RS52500B (de)
RU (1) RU2316326C2 (de)
SI (2) SI1450799T1 (de)
WO (1) WO2003047579A1 (de)
ZA (1) ZA200404225B (de)

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