EP1581534A2 - Dérivés d'azepinones condensées inhibiteurs de tumeurs - Google Patents

Dérivés d'azepinones condensées inhibiteurs de tumeurs

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Publication number
EP1581534A2
EP1581534A2 EP03767828A EP03767828A EP1581534A2 EP 1581534 A2 EP1581534 A2 EP 1581534A2 EP 03767828 A EP03767828 A EP 03767828A EP 03767828 A EP03767828 A EP 03767828A EP 1581534 A2 EP1581534 A2 EP 1581534A2
Authority
EP
European Patent Office
Prior art keywords
compound
general formula
hydrogen
substituted
halogen
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.)
Withdrawn
Application number
EP03767828A
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German (de)
English (en)
Inventor
Bernhard Keppler
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.)
Faustus Forschungs Cie Translational Cancer Research GmbH
Original Assignee
Faustus Forschungs Cie Translational Cancer Research 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 Faustus Forschungs Cie Translational Cancer Research GmbH filed Critical Faustus Forschungs Cie Translational Cancer Research GmbH
Publication of EP1581534A2 publication Critical patent/EP1581534A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic Table without C-Metal linkages

Definitions

  • the present invention relates to fused azepinone derivatives, a process for their preparation, metal complexes of fused azepinone derivatives, and their use for the treatment of tumor diseases.
  • CDKs cyclin-dependent kinases
  • a deregulation of the activity of cyclin dependent kinases can be observed in many human tumors. These are based either on the overexpression of cyclins or on the lack of corresponding natural inhibitors due to genetic changes. Therefore, CDKs represent an attractive class of targets for the chemotherapeutic control of tumor diseases.
  • there are so far only a few substances that are able to act as selective CDK inhibitors with flavopiridol, roscovitins and the purvalanols being important compounds or connection classes are to be mentioned.
  • Annellated azepinones represent another important class of CDK inhibitors.
  • the basic body of this class of compounds allows a number of modifications to optimize the structure with a view to the biological effectiveness.
  • the class of indolo [3,2-d] benzazepinones in particular is a class of compounds whose potential as CDK inhibitors is currently being intensively investigated.
  • substituted azepinones are described in WO 99/65910 as inhibitors of cyclin-dependent kinases.
  • WO 01/60374 also discloses the use of suitably substituted azepinone derivatives for the production of medicaments which contain inhibitors for GSK-3 ⁇ , CDK1 or CDK5.
  • the substitution pattern on the two aryl rings of the tetracyclic base body of the corresponding azepinone derivatives was varied. Replacing the lactam carbonyl group in the azepinone ring with a thioimidate or a hydroxyimidate group did not result in any improvement in biological activity (Schultz et al. J. Med. Chem. 1999, 42, 2909-2919).
  • the object of the present invention is to provide compounds for the treatment of cancer which are highly effective.
  • X is selected from the following groups (a), (b), (c)
  • R 1 , R 2 and R 11 -R 15 are independently selected from the group consisting of hydrogen, halogen, hydroxyl and substituted or unsubstituted cycloalkyl, cycloalkenyl, aryl, substituted or unsubstituted, linear or branched alkyl, alkenyl and alkynyl, and
  • R 3 -R 10 and R 16 -R 20 are independently selected from the group consisting of hydrogen, amino, nitro, cyano, formyl, carboxyl, SO 3 H, SO 3 M b , where M is a physiologically compatible cation, hydroxy , Halogen and substituted or unsubstituted cycloalkyl, cycloalkenyl, aryl, substituted or unsubstituted, linear or branched alkyl, alkenyl, alkynyl, alkoxy, alkylmercapto and dialkylamino, and
  • R 1 and R 2 are as defined above,
  • R 3 -R 10 and R 16 -R 20 are as defined above, and
  • M a Ga, Fe, Ru, or La
  • Y is a physiologically acceptable anion
  • i 2 or 3
  • n 1 or 2
  • x is 0, 1, 2, or 3
  • z is 1, 2 or 3
  • the present invention further relates to a complex of the general formula (III ')
  • M a , L and Y are as defined above.
  • the invention further relates to a compound of the general formula (VI)
  • R 21 and R 22 are independently selected from the group consisting of hydrogen, halogen, hydroxyl and substituted or unsubstituted cycloalkyl, cycloalkenyl, aryl, substituted or unsubstituted, linear or branched alkyl, alkenyl and alkynyl,
  • R 23 to R 30 are independently selected from the group consisting of hydrogen, amino, nitro, cyano, formyl, carboxyl, hydroxy, halogen, SO 3 H, SO 3 M b , where M b is a physiologically acceptable cation, and substituted or unsubstituted cycloalkyl, cycloalkenyl, aryl, substituted or unsubstituted, linear or branched alkyl, alkenyl, alkynyl, alkoxy, alkylmercapto and dialkylamino,
  • R ⁇ b to R M is SO 3 H or SO 3 M b , where M is a physiologically tolerated cation, and physiologically acceptable addition salts thereof.
  • the present invention further relates to a process for the preparation of a complex of the general formula (III)
  • M a and Y are as defined above and m is 1, 2 or 3, and
  • i, n, x, and z are as defined above.
  • the present invention further relates to a process for the preparation of a complex of the general formula (IM ')
  • R 1 and R 2 are as defined above,
  • R 3 -R 10 and R 16 -R 20 are as defined above,
  • M a is as defined above
  • Y is a physiologically acceptable anion
  • q 1, 2 or 3
  • m or q is 3 when Y is a monovalent anion.
  • alkyl in the sense of the present invention preferably contain 1 to 10, more preferably 1 to 6 and in particular 1 to 3 carbon atoms, alkenyl or alkynyl preferably 2 to 10, more preferably 2 to 6 and in particular 2 to 3 carbon atoms, cycloalkyl or cycloalkenyl, preferably 3 to 10, more preferably 3 to 8 and especially 3 to 6 carbon atoms and aryl preferably 6 to 14, more preferably 6 to 10 and especially 6 carbon atoms.
  • R 1 and R 2 ; R 3 to R 6 ; R to R 10 ; Rn to R- ⁇ ; R-I6 to R 20 ; R 2 ⁇ and R 22 ; R 23 to R 26 ; R 27 to R 30 ; and X in the general formulas (I), (II), (IV) or (VI) are substituted, the substituents in these groups are independently of one another preferably halogen, hydroxyl, alkyl, alkoxy, alkoxycarbonyl, alkylmercapto, amino, dialkylamino, dialkylaminocarbonyl and / or nitrile, more preferably hydroxyl, amino and / or CC 4 dialkylamino and in particular hydroxyl and / or CrC 4 dialkylamino.
  • 1 to 3 substituents, in particular 1 substituent are preferably present.
  • substituted groups R 3 -R 10 , R 6 -R 20 and X in the general formulas (I), (II) or (IV) and R 23 -R 30 in the general formula (VI) are preferred independently selected from the group consisting of haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkylene, alkoxycarbonyl, alkoxycarbonylalkylene, alkylmercapto, alkylmercaptoalkylene, dialkylamino, dialkylaminoalkylene, dialkylaminocarbonyl, dialkylaminocarbonylalkylene and alkyl nitrile.
  • R 1 , R 2 and R 11 -R 15 in the general formulas (I), (II) or (IV) and R 21 and R 22 in the general formula (VI) are preferably selected independently of one another from the group consisting of Hydrogen, dC 6 - alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkenyl, C 6 - C 4 aryl, halogen and hydroxyl , more preferably from hydrogen and C-rC 6 alkyl and especially hydrogen.
  • R 3 -R 10 , R 16 -R 20 in the general formulas (I), (II) or (IV) and R 23 -R 30 in the general formula (VI) are preferably selected independently of one another from the group consisting of Hydrogen, C 1 -C 6 alkyl, C 2 -C 6 -
  • M b is a physiologically compatible cation, hydroxy, halogen, C 1 -C 4 -haloalkyl, dd-hydroxyalkyl, d-Ot-alkyl nitrile, dd- Alkoxy, dd-alkoxy-dd-alkylene, dd-alkylmercapto, dC -alkylmercapto-CrC -alkylene, C ⁇ -C 4 -alkoxycarbonyl, dd-alkoxycarbonyl-C-rd-alkylene, di-dC 4 -alkyl-amino, di- dC 4 -alkylamino- dd-alkylene, di-dC -alkylaminocarbonyl and di-dC 4 -alkylaminocarbonyl-
  • C 1 -C 4 -alkylene more preferably from hydrogen, nitro, halogen and dC 6 - alkyl, and in particular from hydrogen and halogen.
  • R 1 , R 2 and R 1 -R 15 in the general formulas (I), (II) or (IV) and R 21 and R 22 in the general formula (VI) are preferably selected independently of one another from the group consisting of Hydrogen, dC 6 - alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkenyl, C 6 - C 14 aryl, halogen and hydroxyl , more preferably from hydrogen and dC 6 - alkyl and especially hydrogen, and
  • R 3 -R 10 , R 16 -R 20 in the general formulas (I), (II) or (IV) and R 23 -R 30 in the general formula (VI) independently of one another selected from the group consisting of hydrogen, CC 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkyny), C 3 -C 6 cycloalkyl, C 3 -C 6 -Cycloalkenyl, C 6 -C 1 -aryl, amino, nitro, cyano, formyl, carboxyl, SO 3 H, SO 3 M b , where M b is a physiologically compatible cation, hydroxy, halogen, CC 4 -haloalkyl, C ⁇ - C 4 hydroxyalkyl, C 4 alkyl nitrile, d C 4 alkoxy, CrC 4 alkoxy dC 4 alkylene, dC 4 alkyl mercapto, CC 4 alkyl mercapto C 4 al
  • R 1 -R 6 and R 11 -R 20 in the general formulas (I), (II) or (IV) are particularly preferably hydrogen, and
  • R 7 -R 10 are independently selected from the group consisting of hydrogen, -CC 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 5 cycloalkyl, C 3 - , C 6 -cycloalkenyl, C 6 -C 14 -aryl, amino, nitro, cyano, formyl, carboxyl, SO 3 H, SO 3 M b , where M is a physiologically compatible cation, hydroxy, halogen, dC 4 -haloalkyl, dC 4 -hydroxyalkyl, CrC 4 -alky) nitrile, CC 4 -alkoxy, Cd-alkoxy-dC 4 -alkylene, C ⁇ -C -alkylmercapto, C- ⁇ -C 4 -alkylmercapto-dC 4 -alkylene, dd-alkoxycarbonyl , dC 4 -alk
  • R 1 -R 8 and R 10 -R 20 in the general formulas (I), (II) or (IV) are very particularly preferably hydrogen
  • R 9 is nitro, cyano, halogen or trifluoromethyl, in particular R 9 is a nitro group or a halogen, bromine being very particularly preferred among the halogens.
  • M a in the general formulas (III), (III '), (V) or (V) is preferably Ga.
  • R 21 -R 28 and R 30 in the general formula (VI) are particularly preferably hydrogen or dC 6 -alkyl, in particular hydrogen.
  • R 29 is particularly preferably SO 3 H or SO 3 M b , where M b is a physiologically compatible cation.
  • R 21 -R 28 and R 30 in the general formula (VI) are preferably hydrogen and R 29 SO 3 H or SO 3 M bl wherein M is a physiologically tolerated cation.
  • M is preferably sodium, potassium or ammonium.
  • X is preferably -CC 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkenyl or C 6 -C 4 aryl ,
  • the substituents of X are preferably selected from hydroxyl, amino and dC 4 dialkylamino.
  • XCC 6 alkyl is particularly preferred.
  • the substituents of X are particularly preferably selected from hydroxyl and dC 4 dialkylamino.
  • X is dC 6 alkyl and substituted by hydroxyl or dd-dialkylamino.
  • the connections KP1428, KP1436, KP1437, KP1438, KP1472 and KP1473 shown in the examples are particularly preferred.
  • the compound KP1428 can contain CH 3 OH from the synthesis.
  • the compounds KP1437 and KP1438 can contain water and the compounds KP1472 and KP1473 from the synthesis CH 3 CH 2 OH.
  • Organic or inorganic addition salts can be formed with the following anions:
  • Chloride bromide, phosphate, carbonate, nitrate, perchlorate, sulfate, citrate, lactate, Tartrate, maleate, fumarate, mandelate, benzoate, ascorbate, cinnamate, glycollate, methanesulfonate, formate, malonate, naphthalene-2-sulfonate, salicylate and / or acetate.
  • Y is preferably selected from the group consisting of halogens, pseudohalogens, nitrate, carboxylate, sulfate, carbonate, hydrogen phosphate, tartrate, malonate, oxalate and R " COO, where R " is hydrogen, Ci-C ⁇ -alkyl, C 2 - C ⁇ -alkenyl , C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkenyl, C 6 -C 14 aryl, or a heterocycle.
  • Y is particularly preferably a halogen, in particular chlorine.
  • the compounds or complexes according to the invention can contain water of crystallization or solvent molecules such as methanol or ethanol.
  • i is preferably 3. Furthermore, i is 2 or 3 if M a is Ru or Fe, ie is in oxidation state II or III, and 3 if M a is Ga, ie in oxidation state III present
  • n is preferably 1.
  • x is preferably 0 or 1 and in particular 0.
  • z is 1 or 2 and in particular 2.
  • j is preferably 0 or 1. More preferably, j is 0 or 1 if M a is Ru or Fe, ie is in the oxidation state II or III, and 1 if M a is Ga, ie in oxidation level III is present.
  • the compound according to the invention can be used for the prophylaxis and / or treatment of cancer.
  • the medicament according to the invention is administered primarily intravenously, but also intramuscularly, intraperitoneally, subcutaneously or orally. External application is also possible. Administration by intravenous injection or intravenous infusion is preferred.
  • the medicament is produced by methods known per se, the compound according to the invention being used as such or, if appropriate, in combination with suitable pharmaceutical carriers. If the medicament according to the invention contains pharmaceutical carriers in addition to the active substance, the active substance content of this mixture is 0.1 to 99.5, preferably 0.5 to 95% by weight of the total mixture.
  • the medicament according to the invention can be used in any suitable formulation, provided that the formation or maintenance of sufficient active substance levels is ensured. This can be achieved, for example, by oral or parenteral administration in suitable doses.
  • the pharmaceutical preparation of the active ingredient is advantageously in the form of unit doses which are tailored to the desired administration.
  • a unit dose can be, for example, a tablet, a dragee, a capsule, a suppository or a measured volume of a powder, a granulate, a solution, an emulsion or a suspension.
  • unit dose is understood to mean a physically determined unit which contains an individual amount of the active ingredient in combination with a pharmaceutical carrier and whose active ingredient content corresponds to a fraction or multiples of a single therapeutic dose.
  • a single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half, a third or a quarter of a daily dose.
  • the unit dose is advantageously divisible, for example in the form of a tablet with a notch.
  • the pharmaceuticals according to the invention if they are in unit doses and for applications e.g. are intended for humans, contain about 0.1 to 500 mg, preferably 10 to 200 mg and in particular 50 to 150 mg of active ingredient.
  • the active ingredient (s) are administered in a daily dose of 0.1 to 5, preferably 1 to 3 mg / kg body weight, optionally in the form of several, preferably 1 to 3, single doses to achieve the desired results.
  • a single dose contains the active ingredient (s) in amounts of 0.1 to 5, preferably 1 to 3 mg / kg body weight. Similar doses can be used in oral treatment.
  • the therapeutic administration of the medicament according to the invention can take place 1 to 4 times a day at fixed or varying times, e.g. before meals and / or in the evening. However, it may be necessary to deviate from the doses mentioned, depending on the type, body weight and age of the individuals to be treated, the type and severity of the disease, the type of preparation and administration of the medicinal product, and the period or Interval within which the administration takes place. In some cases, it may be sufficient to make do with less than the above-mentioned amount of active ingredient, while in other cases the above-mentioned amount of active ingredient must be exceeded. It may also be useful to administer the medication only once or several days apart.
  • Any specialist based on his or her specialist knowledge, can determine the required optimal dosage and type of application of the active ingredients.
  • the pharmaceuticals according to the invention generally consist of the compounds according to the invention and non-toxic, pharmaceutical compatible pharmaceutical carriers which are used as admixtures or diluents, for example in solid, semi-solid or liquid form or as enveloping agents, for example in the form of a capsule, a tablet cover, a sachet or another container for the therapeutically active ingredient.
  • a carrier can serve, for example, as a mediator for the absorption of pharmaceuticals by the body, as a formulation aid, as a sweetener, as a taste corrector, as a color or as a preservative.
  • Tablets dragees e.g. come from gelatin, dispersible powders, granules, aqueous and oily suspensions, emulsions, solutions or syrups.
  • Tablets can contain inert diluents, e.g. Calcium carbonate, calcium phosphate, sodium phosphate or lactose; Granulation and
  • Distribution means e.g. Corn starch or alginates; Binders, e.g. Strength,
  • Gelatin or acacia Gelatin or acacia
  • lubricants e.g. Aluminum or magnesium
  • Magnesium stearate, talc or silicone oil You can also be provided with a coating, which can also be such that it delayed dissolution and absorption of the drug preparation in the
  • Gastrointestinal tract so that e.g. better tolerance
  • Gelatin capsules can be made of any material that Contracting or retardation is achieved. Gelatin capsules can be made of any material that Contracting or retardation is achieved. Gelatin capsules can be made of any material that Contracting or retardation is achieved. Gelatin capsules can be made of any material that Contracting or retardation is achieved. Gelatin capsules can be made of any material. Contracting or retardation is achieved. Gelatin capsules can be made of any material. Contracting or retardation is achieved. Gelatin capsules can be made of Contracting or retardation.
  • Drug mixed with a solid e.g. Calcium carbonate or kaolin, or an oily, e.g. Olive, peanut, or paraffin oil, diluent included.
  • a solid e.g. Calcium carbonate or kaolin
  • an oily e.g. Olive, peanut, or paraffin oil, diluent included.
  • Aqueous suspensions can include suspending agents, e.g.
  • Dispersing and wetting agents for example polyoxyethylene stearate, heptadecaethyleneoxycatanol, polyoxyethylene sorbitol monooleate or lecithin; Preservatives, for example methyl or propyl hydroxybenzoates; Flavoring agents; Sweeteners, for example sucrose, lactose, sodium cyclamate, dextrose, invert sugar syrup, contain. Oily suspensions can include peanut, olive, sesame, coconut or
  • Paraffin oil and thickeners such as e.g. Beeswax, hard paraffin or
  • Cetyl alcohol also sweeteners, flavoring agents and antioxidants.
  • Water-dispersible powders and granules may contain the compound of the invention in admixture with dispersing, wetting and suspending agents e.g. the above, as well as with sweeteners, flavorings and colorants.
  • Emulsions can e.g. Olive, peanut, or paraffin oil in addition to emulsifiers, such as Acacia, tragacanth, phosphatides, sorbitan monooleate, polyoxyethylene sorbitan monooleate, and sweeteners and flavoring agents.
  • emulsifiers such as Acacia, tragacanth, phosphatides, sorbitan monooleate, polyoxyethylene sorbitan monooleate, and sweeteners and flavoring agents.
  • Aqueous solutions can contain preservatives, e.g. Methyl or propyl hydroxybenzoates; Thickener; Flavoring agents; Sweeteners, e.g. Contain sucrose, lactose, sodium cyclamate, dextrose, invert sugar syrup, as well as flavorings and colorings.
  • preservatives e.g. Methyl or propyl hydroxybenzoates
  • Thickener e.g. Methyl or propyl hydroxybenzoates
  • Flavoring agents e.g. Contain sucrose, lactose, sodium cyclamate, dextrose, invert sugar syrup, as well as flavorings and colorings.
  • Sterile injectable, aqueous solutions, isotonic saline solutions or other solutions are used for parenteral use of the medicinal substances.
  • KP1436 (170 mg, 4.9 mmol) was heated to boiling in methanol (30 mL) and 2-hydroxybenzaldehyde (60 mg, 4.9 mmol) in methanol (1 mL) was added. The reaction mixture was refluxed for 15 minutes. After the starting material had completely dissolved, KP1437 began to crystallize out. At this point a solution of GaCI 3 (2.45 mmol) in ethanol (0.3 mL) was added. The solution thus obtained was heated to reflux for 20 minutes and then left to stand at room temperature. The next day the precipitate was filtered off, washed with cold methanol and dried in vacuo. Yield: 90 mg.
  • the mixture was then slowly evaporated to about% at an oil bath temperature of 57-60 ° C. while drawing in air through an inlet tube with cotton plugs, the product precipitating out as a fine crystalline precipitate.
  • the mixture was then cooled in a freezer (-20 ° C.) before being filtered off in a suction filter, washed 3 times with 10 ml of cooled (-20 ° C.) ethanol (96%) and sucked dry.
  • the tumor-inhibiting effect was tested in the XTT assay using the example of various cell lines in vitro.
  • the incubation period was 48 hours (IC 50 values in ⁇ M).

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  • 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)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

L'invention concerne des dérivés d'azépinones condensées, un procédé pour leur production, des complexes métalliques desdits dérivés d'azépinones condensées, ainsi que leur utilisation pour le traitement de maladies tumorales.
EP03767828A 2002-12-23 2003-12-23 Dérivés d'azepinones condensées inhibiteurs de tumeurs Withdrawn EP1581534A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10260618 2002-12-23
DE10260618A DE10260618B4 (de) 2002-12-23 2002-12-23 Tumorhemmende annellierte Azepinonderivate
PCT/EP2003/014831 WO2004058766A2 (fr) 2002-12-23 2003-12-23 Derives d'azepinones condensees inhibiteurs de tumeurs

Publications (1)

Publication Number Publication Date
EP1581534A2 true EP1581534A2 (fr) 2005-10-05

Family

ID=32477925

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03767828A Withdrawn EP1581534A2 (fr) 2002-12-23 2003-12-23 Dérivés d'azepinones condensées inhibiteurs de tumeurs

Country Status (7)

Country Link
US (1) US20060009445A1 (fr)
EP (1) EP1581534A2 (fr)
JP (1) JP2006515591A (fr)
AU (1) AU2003292264A1 (fr)
CA (1) CA2551576A1 (fr)
DE (1) DE10260618B4 (fr)
WO (1) WO2004058766A2 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104262409B (zh) * 2014-09-29 2017-02-01 广西中医药大学 一种用于治疗肝癌的有机化合物及其制备方法和用途

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1086105B1 (fr) * 1998-06-16 2006-03-01 THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES Inhibiteurs de kinases dependantes de la cycline sous forme d'azepinone fusionnee
FR2804959B1 (fr) * 2000-02-15 2006-04-28 Centre Nat Rech Scient Utilisation de derives de paullones pour la fabrication de medicaments

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2004058766A2 *

Also Published As

Publication number Publication date
JP2006515591A (ja) 2006-06-01
AU2003292264A1 (en) 2004-07-22
CA2551576A1 (fr) 2004-07-15
US20060009445A1 (en) 2006-01-12
DE10260618B4 (de) 2005-06-09
WO2004058766A2 (fr) 2004-07-15
DE10260618A1 (de) 2004-07-08
WO2004058766A3 (fr) 2004-08-26

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