WO1994006771A1 - 1,2 DYHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3-DIONES ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCEREUX - Google Patents

1,2 DYHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3-DIONES ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCEREUX Download PDF

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Publication number
WO1994006771A1
WO1994006771A1 PCT/US1993/008640 US9308640W WO9406771A1 WO 1994006771 A1 WO1994006771 A1 WO 1994006771A1 US 9308640 W US9308640 W US 9308640W WO 9406771 A1 WO9406771 A1 WO 9406771A1
Authority
WO
WIPO (PCT)
Prior art keywords
dione
dihydro
deh
dibenz
isoquinoline
Prior art date
Application number
PCT/US1993/008640
Other languages
English (en)
Other versions
WO1994006771A9 (fr
Inventor
David S. Alberts
Robert T. Dorr
William A. Remers
Salah M. Sami
Original Assignee
Research Corporation Technologies, Inc.
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 Research Corporation Technologies, Inc. filed Critical Research Corporation Technologies, Inc.
Priority to JP50823794A priority Critical patent/JP3543196B2/ja
Priority to EP93922191A priority patent/EP0660824A1/fr
Priority to AU51278/93A priority patent/AU5127893A/en
Priority to US08/142,283 priority patent/US5635506A/en
Publication of WO1994006771A1 publication Critical patent/WO1994006771A1/fr
Publication of WO1994006771A9 publication Critical patent/WO1994006771A9/fr

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Classifications

    • 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
    • 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
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/18—Ring systems of four or more rings
    • 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
    • C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • R 12 and R 13 are independently hydrogen or lower alkyl which is unsubstituted or substituted with hydroxy, mercapto, lower alkoxy, lower alkylcarbonyloxy, carboxy or carboloweralkoxy, or R 12 and R 13 taken together with the nitrogen atom to which they are attached form a 3 to 6-membered heterocyclic ring;
  • diloweralkylaminoloweralkyleneoxy refers to a lower alkyleneoxy group as defined
  • NR 12 group together with D may form a 5 or 6 membered nitrogen heterocyclic ring, such as a piperidine or pyrrolidine, e.g..
  • R 12 , R 13 , n 3 , R 6 , R 8 and R 10 are as defined hereinabove, and n 4 is 0 or 1.
  • Sterile injectable solutions are prepared by incorporating the active compound in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization.
  • dispersions are prepared by incorporating the various sterilized active ingredient into a sterile vehicle which contains the basic dispersion medium and the required other
  • the compound can be prepared as follows:
  • the compounds of the present invention were evaluated for cytotoxic activities in cloned human colon carcinomas.
  • the clonogenic assays were conducted in accordance with the procedure
  • the tumor cells are processed into a single cell suspension.
  • the cells are plated at a
  • P-388/Adriamycin Resistant Cells The same protocol as above was used for these studies with a multidrug resistant P-388 cell line developed in vivo by and supplied by Dr. Randall Johnson (Johnson RK, et al.,
  • Tumors are measured bidimensionally as described above and tumor growth delay is calculated at times to reach 1.5 and 3.0 g of tumor mass.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)

Abstract

L'invention concerne un composé utile pour le traitement des tumeurs représenté par la formule (I) dans laquelle, R8, R6 et R10 représentent indépendamment hydrogène, alkyle inférieur, aryle, alkanoyle, formyle, halogène, hydrazino, nitro, NR2R3, OR1, ou SR1, méthoxy, hydroxy, CO2H, SO2NR1R2 ou CONR1R2; R1, R2 et R3 représentent indépendamment hydrogène, alkyle inférieur, alkyle inférieur d'aryle, aryle, formyle ou alkanoyle inférieur, R9, R11, R10 et R7 représentent indépendamment hydrogène, ou alkyle inférieur ou R9 et R11 considérés ensemble avec les atomes de carbone auxquels ils sont attachés forment un groupe phényle ou R9 et R10 considérés ensemble avec les atomes de carbone auxquels ils sont attachés forment un groupe phényle ou R7 et R10 considérés ensemble avec les atomes de carbone auxquels ils sont attachés forment un groupe phényle; A représente (CR4R5)n3, cycloalkyle inférieur ou aryle ou une liaison chimique; chaque R4 et R5 représente indépendamment hydrogène ou alkyle inférieur, R12 et R13 représentent indépendamment hydrogène, ou alkyle inférieur non substitué ou substitué par hydroxy, mercapto, alcoxy ou substitué par hydroxy, mercapto, alcoxy inférieur, carbonyloxy d'aryle inférieur, carboxy ou carbo-alcoxy inférieur ou R12 et R13 considérés ensemble avec l'azote auquel ils sont attachés forment un hétérocycle à 3-6 éléments; D représente une liaison chimique ou forme lorsqu'il est considéré avec NR12 un hétérocyle à 5 ou 6 éléments; n1 et n2 représentent indépendamment 0, 1 ou 2; et n3 représente 0, 1, 2, 3, 4 ou 5.
PCT/US1993/008640 1990-06-26 1993-09-13 1,2 DYHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3-DIONES ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCEREUX WO1994006771A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP50823794A JP3543196B2 (ja) 1992-09-11 1993-09-13 ６−エトキシ−２−［２’−（ジメチルアミノ）エチル］−１，２−ジヒドロ−３Ｈ−ジベンズ（ｄｅｈ）−イソキノリン−１，３−ジオン
EP93922191A EP0660824A1 (fr) 1992-09-11 1993-09-13 1,2 DYHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3-DIONES ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCEREUX
AU51278/93A AU5127893A (en) 1992-09-11 1993-09-13 1,2 dihydro-3-h-dibenz(de,h) isoquinoline 1,3 dione and their use as anticancer agents
US08/142,283 US5635506A (en) 1990-06-26 1993-09-13 1, 2-dihydro-3H-dibenzisoquinoline-1,3-dione anticancer agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US94363492A 1992-09-11 1992-09-11
US943,634 1992-09-11

Publications (2)

Publication Number Publication Date
WO1994006771A1 true WO1994006771A1 (fr) 1994-03-31
WO1994006771A9 WO1994006771A9 (fr) 1994-06-09

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1993/008640 WO1994006771A1 (fr) 1990-06-26 1993-09-13 1,2 DYHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3-DIONES ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCEREUX

Country Status (5)

Country Link
EP (1) EP0660824A1 (fr)
JP (1) JP3543196B2 (fr)
AU (1) AU5127893A (fr)
CA (1) CA2144049A1 (fr)
WO (1) WO1994006771A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995029895A1 (fr) * 1994-04-28 1995-11-09 Knoll Aktiengesellschaft Derives dihydrodibenzo(de,h)isoquinolines et leur utilisation en tant qu'agents anticancereux
US6693099B2 (en) 2000-10-17 2004-02-17 The Procter & Gamble Company Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance
US8420665B2 (en) 2008-01-11 2013-04-16 Northwestern University Anti-cancer compounds

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6291425B1 (en) * 1999-09-01 2001-09-18 Guilford Pharmaceuticals Inc. Compounds, methods and pharmaceutical compositions for treating cellular damage, such as neural or cardiovascular tissue damage

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2392978A2 (fr) * 1977-06-04 1978-12-29 Made Labor Sa Naphtalimides substitues utilisables comme medicaments
EP0125439A2 (fr) * 1983-04-01 1984-11-21 Warner-Lambert Company 1,8-Naphtalimides 3,6-disubstituées, leurs procédés de préparation et leur application
WO1992000281A1 (fr) * 1990-06-26 1992-01-09 Research Corporation Technologies, Inc. Agents anticancereux a base de 1,2-dihydro-3h-dibenzisoquinoline-1,3-diones

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2392978A2 (fr) * 1977-06-04 1978-12-29 Made Labor Sa Naphtalimides substitues utilisables comme medicaments
EP0125439A2 (fr) * 1983-04-01 1984-11-21 Warner-Lambert Company 1,8-Naphtalimides 3,6-disubstituées, leurs procédés de préparation et leur application
WO1992000281A1 (fr) * 1990-06-26 1992-01-09 Research Corporation Technologies, Inc. Agents anticancereux a base de 1,2-dihydro-3h-dibenzisoquinoline-1,3-diones

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SALAH M. SAMI ET AL: "2-Substituted 1-2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones.A new class of antitumor agent", JOURNAL OF MEDICINAL CHEMISTRY, vol. 36, no. 6, 19 March 1993 (1993-03-19), WASHINGTON US, pages 765 - 770 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995029895A1 (fr) * 1994-04-28 1995-11-09 Knoll Aktiengesellschaft Derives dihydrodibenzo(de,h)isoquinolines et leur utilisation en tant qu'agents anticancereux
US6693099B2 (en) 2000-10-17 2004-02-17 The Procter & Gamble Company Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance
US8420665B2 (en) 2008-01-11 2013-04-16 Northwestern University Anti-cancer compounds
US8829025B2 (en) 2008-01-11 2014-09-09 Northwestern University Anti-cancer compounds
US9878984B2 (en) 2008-01-11 2018-01-30 Northwestern University Anti-cancer compounds

Also Published As

Publication number Publication date
EP0660824A1 (fr) 1995-07-05
AU5127893A (en) 1994-04-12
JPH08501312A (ja) 1996-02-13
JP3543196B2 (ja) 2004-07-14
CA2144049A1 (fr) 1994-03-31

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