WO2002087574A2 - Utilisation de derives de pyridoindolone pour la preparation de medicaments anticancereux - Google Patents

Utilisation de derives de pyridoindolone pour la preparation de medicaments anticancereux Download PDF

Info

Publication number
WO2002087574A2
WO2002087574A2 PCT/FR2002/001449 FR0201449W WO02087574A2 WO 2002087574 A2 WO2002087574 A2 WO 2002087574A2 FR 0201449 W FR0201449 W FR 0201449W WO 02087574 A2 WO02087574 A2 WO 02087574A2
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
group
hydrogen
formula
pyrido
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.)
Ceased
Application number
PCT/FR2002/001449
Other languages
English (en)
French (fr)
Other versions
WO2002087574A3 (fr
Inventor
Bernard Bourrie
Pierre Casellas
Jean-Marie Derocq
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.)
Sanofi Aventis France
Original Assignee
Sanofi Synthelabo SA
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
Priority to CA002443012A priority Critical patent/CA2443012C/fr
Priority to EEP200300466A priority patent/EE200300466A/xx
Priority to HK04102775.3A priority patent/HK1059895B/xx
Priority to AT02732841T priority patent/ATE314070T1/de
Priority to DE60208365T priority patent/DE60208365T2/de
Priority to SK1325-2003A priority patent/SK13252003A3/sk
Priority to UA2003109248A priority patent/UA74876C2/uk
Priority to HU0400744A priority patent/HUP0400744A2/hu
Priority to US10/476,322 priority patent/US6967203B2/en
Priority to IL15831202A priority patent/IL158312A0/xx
Priority to EP02732841A priority patent/EP1385512B1/fr
Priority to MXPA03009639A priority patent/MXPA03009639A/es
Priority to SI200230285T priority patent/SI1385512T1/sl
Priority to JP2002584919A priority patent/JP2004528343A/ja
Application filed by Sanofi Synthelabo SA filed Critical Sanofi Synthelabo SA
Priority to BR0209138-0A priority patent/BR0209138A/pt
Priority to NZ528671A priority patent/NZ528671A/en
Publication of WO2002087574A2 publication Critical patent/WO2002087574A2/fr
Publication of WO2002087574A3 publication Critical patent/WO2002087574A3/fr
Priority to IL158312A priority patent/IL158312A/en
Priority to IS6984A priority patent/IS2441B/is
Priority to NO20034787A priority patent/NO20034787L/no
Anticipated expiration legal-status Critical
Priority to US11/204,275 priority patent/US7160895B2/en
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a new therapeutic application of pyridoindolone derivatives.
  • R ⁇ represents a hydrogen atom or a methyl or ethyl group
  • R2 represents a methyl or ethyl group
  • - rc represents either a phenyl group optionally substituted by a halogen atom or a methyl or methoxy group, or a thienyl group;
  • R4 represents a hydrogen or chlorine atom or a methyl or methoxy group.
  • the compounds of formula (I) having an affinity for the omega modulating sites associated with GABA ⁇ receptors can be used in the treatment of conditions linked to disorders of gabaergic transmission associated with GABAA receptor subtypes, such as anxiety, sleep disturbances, epilepsy, etc.
  • the compounds of formula (I) are anticancer agents, inhibiting the proliferation of tumor cells, which have antimitotic properties.
  • the subject of the invention is the use of the compounds of formula (I) as defined above, of their pharmaceutically acceptable salts, hydrates or solvates, for the preparation of medicaments useful as anticancer agents.
  • Preferred compounds according to the invention are the compounds of formula: in which :
  • - Ri represents a hydrogen atom, a methyl or ethyl group
  • R2 represents a methyl or ethyl group
  • R 3 represents a hydrogen or halogen atom or a methyl or methoxy group
  • R4 represents a hydrogen or chlorine atom or a methyl or methoxy group.
  • Particularly preferred compounds according to the invention are the compounds of formula:
  • Rj represents a hydrogen atom, a methyl or ethyl group
  • R2 represents a methyl or ethyl group
  • R3 represents a hydrogen or halogen atom or a methyl or methoxy group
  • R4 represents a hydrogen or chlorine atom or a methyl or methoxy group.
  • More particularly preferred compounds according to the invention are the compounds of formula: in which :
  • - Ri represents a methyl or ethyl group
  • R2 represents a methyl or ethyl group
  • R3 represents a hydrogen or halogen atom or a methyl or methoxy group
  • R4 represents a hydrogen or chlorine atom or a methyl or methoxy group.
  • the compounds of the invention are the following:
  • the compounds of formula (I) according to the present invention were tested in vitro on a human breast cancer cell line: the line MDA-MB-231 available from the American Type Culture Collection (reference HTB26).
  • the evaluation of the antiproliferative effect is carried out according to JM Derocq et al., FEBS Letters, 1998, 425, 419-425: the degree of incorporation of [3 H] thymidine into the DNA of the treated cells is measured, after 96 hours of incubation of a compound of formula (I).
  • the inhibitory concentration 50 (IC50) is defined as the concentration which inhibits cell proliferation by 50%.
  • the compounds according to the invention have an IC50 generally less than 10 ⁇ M on the MDA-MB-231 line.
  • MDR line from the English multi-drug-resistant
  • MDA-Ai MDA-Ai
  • multi-resistant which qualifies this line, means that said line is generally insensitive to the chemotherapy drugs commonly used and in particular to antimitotics of natural origin such as paclitaxel, vincristine, vinblastine.
  • the compounds according to the invention have an IC50 generally less than 10 ⁇ M on the MDA-Ai multi-resistant line.
  • the compounds of formula (I) inhibit the proliferation of tumor cells including the proliferation of cells having a multi-resistance.
  • the treatment of animals with a compound according to the invention begins 6 to 7 days after implantation, when the tumor reaches a tumor mass of approximately 60 mg.
  • the compound, in solution in a solvent, is then administered orally.
  • the antitumor activity is evaluated when the average tumor mass reaches approximately 1000 mg in the control animals, treated with the solvent only: the T / C ratio is measured, T representing the average weight of the tumors in the treated animals and C representing the weight by means of tumors in control animals.
  • a T / C ratio less than or equal to 42% is considered to be an indicator of significant antitumor activity according to Stuart T et al., In J. Med. Chem., 2001, 44 (11), 1758-1776.
  • T / C ratio less than or equal to 42% is considered to be an indicator of significant antitumor activity according to Stuart T et al., In J. Med. Chem., 2001, 44 (11), 1758-1776.
  • For a cumulative daily dose administered between 50 and 300 mg / kg, certain compounds according to the invention have led to a T / C ratio of less than 20%.
  • the compounds of formula (I), their pharmaceutically acceptable salts, hydrates or solvates, are useful for preventing or treating diseases caused or exacerbated by the proliferation of tumor cells, such as primary or metastatic tumors, carcinomas and cancers, in particular : breast cancer ; lung cancer ; cancer of the small intestine, cancer of the colon and rectum; cancer of the respiratory tract, oropharynx and hypopharynx; esophageal cancer; cancer liver, stomach cancer, bile duct cancer, gallbladder cancer, pancreatic cancer; urinary tract cancers including kidney, urothelium, and bladder; cancers of the female genital tract including cancer of the uterus, cervix, ovaries, chloriocarcinoma and trophoblastoma; cancers of the male genital tract including cancer of the prostate, seminal vesicles, testes, germ cell tumors; cancers of the endocrine glands including cancer of the thyroid, pituitary gland, adrenal glands;
  • the compounds of formula (I) above can be used in daily doses of 0.002 to 2000 mg per kilogram of body weight of the mammal to be treated, preferably in daily doses of 0.1 to 300 mg / kg.
  • the dose may preferably vary from 0.02 to 10,000 mg per day, more particularly from 1 to 3000 mg, depending on the age of the subject to be treated or the type of treatment (prophylactic or curative).
  • the present invention relates to pharmaceutical compositions comprising, as active principle, an effective dose of at least one compound according to the invention, or a pharmaceutically acceptable salt, a hydrate or a solvate of said compound, as well as one or more pharmaceutically acceptable excipients.
  • Said excipients are chosen according to the pharmaceutical form and the desired mode of administration, from the usual excipients which are known in the prior art.
  • compositions of the present invention can be prepared for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal administration to animals and humans for prevention or treatment. of the above diseases.
  • Suitable administration forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, forms for sublingual, oral, intratracheal, intraocular, intranasal, inhalation, forms for topical, transdermal, subcutaneous, intramuscular or intravenous administration, forms for rectal administration and implants.
  • the compounds according to the invention can be used in creams, gels, ointments or lotions.
  • the appropriate dosage for each patient is determined by the doctor according to the mode of administration, the age, the weight and the response of said patient.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/FR2002/001449 2001-04-27 2002-04-26 Utilisation de derives de pyridoindolone pour la preparation de medicaments anticancereux Ceased WO2002087574A2 (fr)

Priority Applications (20)

Application Number Priority Date Filing Date Title
SI200230285T SI1385512T1 (sl) 2001-04-27 2002-04-26 Uporaba derivatov piridoindolona za pripravo zdravil proti raku
HK04102775.3A HK1059895B (en) 2001-04-27 2002-04-26 Use of pyridoindolone derivatives for preparing anticancer medicines
AT02732841T ATE314070T1 (de) 2001-04-27 2002-04-26 Verwendung von pyridoindolonderivaten zur herstellung von antikrebsmitteln
DE60208365T DE60208365T2 (de) 2001-04-27 2002-04-26 Verwendung von pyridoindolonderivaten zur herstellung von antikrebsmitteln
SK1325-2003A SK13252003A3 (sk) 2001-04-27 2002-04-26 Použitie derivátov pyridoindolónu na prípravu protinádorových liečiv
UA2003109248A UA74876C2 (en) 2001-04-27 2002-04-26 Use of pyridoindolon derivatives for producing anticancer drugs
HU0400744A HUP0400744A2 (hu) 2001-04-27 2002-04-26 Piridoindolon származékok felhasználása rákellenes gyógyszerek előállítására
US10/476,322 US6967203B2 (en) 2001-04-27 2002-04-26 Use of pyridoindolone derivatives for preparing anticancer medicines
EEP200300466A EE200300466A (et) 2001-04-27 2002-04-26 Püridoindolooni derivaatide kasutamine ravimite valmistamiseks
EP02732841A EP1385512B1 (fr) 2001-04-27 2002-04-26 Utilisation de derives de pyridoindolone pour la preparation de medicaments anticancereux
MXPA03009639A MXPA03009639A (es) 2001-04-27 2002-04-26 Uso de derivados de piridoindolona para preparar medicinas anticancer.
CA002443012A CA2443012C (fr) 2001-04-27 2002-04-26 Utilisation de derives de pyridoindolone pour la preparation de medicaments
IL15831202A IL158312A0 (en) 2001-04-27 2002-04-26 Use of pyridoindole derivatives for preparing anticancer medicines
JP2002584919A JP2004528343A (ja) 2001-04-27 2002-04-26 抗癌薬の製造のためのピリドインドロン誘導体の使用
BR0209138-0A BR0209138A (pt) 2001-04-27 2002-04-26 Utilização de derivados de piridoindolona para a preparação de medicamentos
NZ528671A NZ528671A (en) 2001-04-27 2002-04-26 Use of pyridoindolone derivatives for preparing anticancer medicines
IL158312A IL158312A (en) 2001-04-27 2003-10-08 Use of pyridoindolone derivatives for preparing anticancer medicines
IS6984A IS2441B (is) 2001-04-27 2003-10-09 Notkun á pýridóindólon afleiðum til framleiðslu lyfja gegn krabbameini
NO20034787A NO20034787L (no) 2001-04-27 2003-10-24 Anvendelse av pyridoindolonderivater var fremstilling av anticancer-medisiner
US11/204,275 US7160895B2 (en) 2001-04-27 2005-08-15 Use of pyridoindolone derivatives for the preparation of medicinal products

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0105843A FR2823975B1 (fr) 2001-04-27 2001-04-27 Nouvelle utilisation de pyridoindolone
FR01/05843 2001-04-27

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10476322 A-371-Of-International 2002-04-26
US11/204,275 Continuation US7160895B2 (en) 2001-04-27 2005-08-15 Use of pyridoindolone derivatives for the preparation of medicinal products

Publications (2)

Publication Number Publication Date
WO2002087574A2 true WO2002087574A2 (fr) 2002-11-07
WO2002087574A3 WO2002087574A3 (fr) 2003-02-13

Family

ID=8862882

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/FR2002/001449 Ceased WO2002087574A2 (fr) 2001-04-27 2002-04-26 Utilisation de derives de pyridoindolone pour la preparation de medicaments anticancereux
PCT/FR2002/001450 Ceased WO2002087575A1 (fr) 2001-04-27 2002-04-26 Associations pharmaceutiques a base de derives de pyridoindolone et d'agents anticancereux

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/FR2002/001450 Ceased WO2002087575A1 (fr) 2001-04-27 2002-04-26 Associations pharmaceutiques a base de derives de pyridoindolone et d'agents anticancereux

Country Status (33)

Country Link
US (3) US6967203B2 (enExample)
EP (2) EP1385512B1 (enExample)
JP (2) JP2004528343A (enExample)
KR (1) KR100847413B1 (enExample)
CN (2) CN1240382C (enExample)
AR (1) AR034313A1 (enExample)
AT (2) ATE314070T1 (enExample)
BG (2) BG108261A (enExample)
BR (1) BR0209138A (enExample)
CA (2) CA2444334A1 (enExample)
CY (1) CY1105813T1 (enExample)
CZ (2) CZ299465B6 (enExample)
DE (2) DE60214533T2 (enExample)
DK (2) DK1385512T3 (enExample)
EA (1) EA005930B1 (enExample)
EE (2) EE200300466A (enExample)
ES (2) ES2271264T3 (enExample)
FR (1) FR2823975B1 (enExample)
HU (2) HUP0400745A2 (enExample)
IL (4) IL158266A0 (enExample)
IS (1) IS2441B (enExample)
MX (1) MXPA03009639A (enExample)
NO (2) NO20034787L (enExample)
NZ (1) NZ528671A (enExample)
PL (2) PL366910A1 (enExample)
PT (2) PT1385513E (enExample)
RS (2) RS50791B (enExample)
RU (1) RU2292888C9 (enExample)
SK (2) SK13242003A3 (enExample)
TW (1) TWI252104B (enExample)
UA (1) UA74876C2 (enExample)
WO (2) WO2002087574A2 (enExample)
ZA (1) ZA200307785B (enExample)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004041817A1 (fr) * 2002-10-23 2004-05-21 Sanofi-Aventis Derives de pyridoindolone substitues en -3 par un phenyle, leur preparation et leur application en therapeutique.
FR2869316A1 (fr) * 2004-04-21 2005-10-28 Sanofi Synthelabo Derives de pyridoindolone substitues en -6, leur preparation et leur application en therapeutique.
US7456193B2 (en) 2002-10-23 2008-11-25 Sanofi-Aventis Pyridoindolone derivatives substituted in the 3-position by a heterocyclic group, their preparation and their application in therapeutics
US8063061B2 (en) 2005-10-20 2011-11-22 Sanofi-Aventis 6-heteroarylpyridoindolone derivatives, their preparation and therapeutic use thereof

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2823975B1 (fr) * 2001-04-27 2003-05-30 Sanofi Synthelabo Nouvelle utilisation de pyridoindolone

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1268772A (en) * 1968-03-15 1972-03-29 Glaxo Lab Ltd NOVEL alpha-CARBOLINE DERIVATIVES, THE PREPARATION THEREOF AND COMPOSITIONS CONTAINING THE SAME
US4263304A (en) 1978-06-05 1981-04-21 Sumitomo Chemical Company, Limited 7 H-indolo[2,3-c]isoquinolines
SU833971A1 (ru) * 1979-07-10 1981-05-30 Ленинградский Химико-Фармацевтическийинститут Способ получени 3-фенил-2-оксо- - КАРбОлиНОВ
SU833972A1 (ru) 1979-10-26 1981-05-30 Институт Физико-Органической Химиии Углехимии Ah Украинской Ccp Имидазо(4,5-с)пиридиний иодиды вКАчЕСТВЕ пРОМЕжуТОчНыХ пРОдуКТОВ дл СиНТЕзА фуНгицидОВ
FR2595701B1 (fr) * 1986-03-17 1988-07-01 Sanofi Sa Derives du pyrido-indole, leur application a titre de medicaments et les compositions les renfermant
US5035252A (en) * 1990-12-14 1991-07-30 Mondre Steven J Nicotine-containing dental floss
EP0581388A1 (en) * 1992-07-30 1994-02-02 Glaxo Group Limited Pyridoindolone Methansulphonate as 5HT and 5HT3 receptor antagonists
EP0755454B1 (en) * 1994-04-13 2008-02-13 The Rockefeller University Aav-mediated delivery of dna to cells of the nervous system
DE19502753A1 (de) * 1995-01-23 1996-07-25 Schering Ag Neue 9H-Pyrido[3,4-b]indol-Derivate
US6486177B2 (en) * 1995-12-04 2002-11-26 Celgene Corporation Methods for treatment of cognitive and menopausal disorders with D-threo methylphenidate
DE19624659A1 (de) * 1996-06-20 1998-01-08 Klinge Co Chem Pharm Fab Neue Pyridylalken- und Pyridylalkinsäureamide
FR2765582B1 (fr) 1997-07-03 1999-08-06 Synthelabo Derives de 3-alkyl-1,9-dihydro-2h-pyrido[2,3-b]indol-2-one leur preparation et leur application en therapeutique
FR2765581B1 (fr) * 1997-07-03 1999-08-06 Synthelabo Derives de 3-aryl-1,9-dihydro-2h-pyrido[2,3-b]indol-2-one, leur preparation et leur application en therapeutique
WO1999051597A1 (en) * 1998-04-02 1999-10-14 Neurogen Corporation Aminoalkyl substituted 5,6,7,8-tetrahydro-9h pyrimidino[2,3-b]indole and 5,6,7,8-tetrahydro-9h-pyrimidino[4,5-b]indole derivatives: crf1 specific ligands
IT1313592B1 (it) 1999-08-03 2002-09-09 Novuspharma Spa Derivati di 1h-pirido 3,4-b indol-1-one.
US20020156016A1 (en) * 2001-03-30 2002-10-24 Gerald Minuk Control of cell growth by altering cell membrane potentials
FR2823975B1 (fr) * 2001-04-27 2003-05-30 Sanofi Synthelabo Nouvelle utilisation de pyridoindolone
FR2846329B1 (fr) 2002-10-23 2004-12-03 Sanofi Synthelabo Derives de pyridoindolone substitues en -3 par un phenyle, leur preparation et leur application en therapeutique
FR2846330B1 (fr) 2002-10-23 2004-12-03 Sanofi Synthelabo Derives de pyridoindolone substitues en -3 par groupe heterocyclique, leur preparation et leur application en therapeutique
US6958347B2 (en) 2002-12-18 2005-10-25 Pfizer Inc. Aminophenanthridinone and aminophenanthridine as NPY-5 antagonists
FR2869316B1 (fr) 2004-04-21 2006-06-02 Sanofi Synthelabo Derives de pyridoindolone substitues en -6, leur preparation et leur application en therapeutique.
FR2892416B1 (fr) 2005-10-20 2008-06-27 Sanofi Aventis Sa Derives de 6-heteroarylpyridoindolone, leur preparation et leur application en therapeutique

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004041817A1 (fr) * 2002-10-23 2004-05-21 Sanofi-Aventis Derives de pyridoindolone substitues en -3 par un phenyle, leur preparation et leur application en therapeutique.
US7390818B2 (en) 2002-10-23 2008-06-24 Sanofi-Aventis Pyridoindolone derivatives substituted in the 3-position by a phenyl, their preparation and their application in therapeutics
US7456193B2 (en) 2002-10-23 2008-11-25 Sanofi-Aventis Pyridoindolone derivatives substituted in the 3-position by a heterocyclic group, their preparation and their application in therapeutics
EA010833B1 (ru) * 2002-10-23 2008-12-30 Санофи-Авентис 3-фенилзамещенный пиридоиндолон, его получение и терапевтическое применение
US7816368B2 (en) 2002-10-23 2010-10-19 Sanofi-Aventis Pyridoindolone derivatives substituted in the 3-position by a heterocyclic group, their preparation and their application in therapeutics
US8012991B2 (en) 2002-10-23 2011-09-06 Sanofi-Aventis Pyridoindolone derivatives substituted in the 3-position by a phenyl, their preparation and their application in therapeutics
HRP20050362B1 (hr) * 2002-10-23 2014-01-31 Sanofi-Aventis 3-fenil supstituirani piridoindolon, njegovo dobivanje i njegova terapijska upotreba
FR2869316A1 (fr) * 2004-04-21 2005-10-28 Sanofi Synthelabo Derives de pyridoindolone substitues en -6, leur preparation et leur application en therapeutique.
WO2005108398A1 (fr) * 2004-04-21 2005-11-17 Sanofi-Aventis Derives de pyridoindolone substitues en -6, leur preparation, leur application en therapeutique.
US7812165B2 (en) 2004-04-21 2010-10-12 Sanofi-Aventis 6-substituted pyridoindolone derivatives, production and therapeutic use thereof
JP4809830B2 (ja) * 2004-04-21 2011-11-09 サノフイ−アベンテイス ６−置換ピリドインドロン誘導体、それらの調製及び治療的使用
US8063061B2 (en) 2005-10-20 2011-11-22 Sanofi-Aventis 6-heteroarylpyridoindolone derivatives, their preparation and therapeutic use thereof

Also Published As

Publication number Publication date
EA200301062A1 (ru) 2004-04-29
CN1240382C (zh) 2006-02-08
AR034313A1 (es) 2004-02-18
US7524857B2 (en) 2009-04-28
IL158266A (en) 2009-09-01
US20040122036A1 (en) 2004-06-24
IL158312A0 (en) 2004-05-12
HUP0400744A2 (hu) 2004-06-28
US6967203B2 (en) 2005-11-22
DK1385513T3 (da) 2007-01-15
NZ528671A (en) 2004-06-25
EA005930B1 (ru) 2005-08-25
IS2441B (is) 2008-11-15
CA2444334A1 (fr) 2002-11-07
US7160895B2 (en) 2007-01-09
BR0209138A (pt) 2004-06-08
YU83903A (sh) 2006-08-17
HK1059895A1 (en) 2004-07-23
DE60208365T2 (de) 2006-09-07
PT1385513E (pt) 2007-01-31
US20050272760A1 (en) 2005-12-08
ATE338548T1 (de) 2006-09-15
BG108261A (bg) 2004-12-30
RU2003130376A (ru) 2005-04-10
CZ20032910A3 (en) 2004-07-14
RU2292888C2 (ru) 2007-02-10
IS6984A (is) 2003-10-09
CA2443012A1 (en) 2002-11-07
NO20034785D0 (no) 2003-10-24
HUP0400745A2 (hu) 2004-08-30
EP1385512B1 (fr) 2005-12-28
UA74876C2 (en) 2006-02-15
BG108260A (bg) 2004-12-30
EP1385513B1 (fr) 2006-09-06
KR100847413B1 (ko) 2008-07-18
EE200300466A (et) 2003-12-15
PL366910A1 (en) 2005-02-07
ATE314070T1 (de) 2006-01-15
JP2004528343A (ja) 2004-09-16
IL158312A (en) 2009-09-01
EP1385513A1 (fr) 2004-02-04
NO20034787L (no) 2003-12-23
CA2443012C (fr) 2009-07-28
FR2823975A1 (fr) 2002-10-31
YU83403A (sh) 2006-08-17
PL366916A1 (en) 2005-02-07
CY1105813T1 (el) 2011-02-02
DK1385512T3 (da) 2006-05-22
RS50790B (sr) 2010-08-31
RS50791B (sr) 2010-08-31
JP2004531538A (ja) 2004-10-14
SK13252003A3 (sk) 2004-03-02
KR20040015138A (ko) 2004-02-18
PT1385512E (pt) 2006-05-31
US20040122027A1 (en) 2004-06-24
HK1060066A1 (en) 2004-07-30
CN1505511A (zh) 2004-06-16
DE60214533T2 (de) 2007-06-21
ZA200307785B (en) 2004-10-06
CZ299465B6 (cs) 2008-08-06
WO2002087575A1 (fr) 2002-11-07
DE60208365D1 (de) 2006-02-02
IL158266A0 (en) 2004-05-12
CZ20032909A3 (en) 2004-06-16
DE60214533D1 (de) 2006-10-19
EP1385512A2 (fr) 2004-02-04
FR2823975B1 (fr) 2003-05-30
ES2254683T3 (es) 2006-06-16
CN1505510A (zh) 2004-06-16
NO20034787D0 (no) 2003-10-24
ES2271264T3 (es) 2007-04-16
TWI252104B (en) 2006-04-01
MXPA03009639A (es) 2004-06-30
CZ295224B6 (cs) 2005-06-15
NO20034785L (no) 2003-12-23
RU2292888C9 (ru) 2007-06-20
SK13242003A3 (sk) 2004-03-02
EE200300465A (et) 2003-12-15
WO2002087574A3 (fr) 2003-02-13

Similar Documents

Publication Publication Date Title
JP3178844B2 (ja) 子宮、卵巣及び乳房における抗増殖活性を有する薬剤の製造のためのフラバノリグナンの利用
US20080293777A1 (en) Weight Loss Treatment
WO2009033281A1 (en) Cancer combination therapy with a selective inhibitor of histone deacetylase hdac1, hdac2 and/or hdac3 and a microtubule stabilizer
EP1385512B1 (fr) Utilisation de derives de pyridoindolone pour la preparation de medicaments anticancereux
WO2019106604A1 (en) Pharmaceutical combination comprising lsz102 and alpelisib
FR2846330A1 (fr) Derives de pyridoindolone substitues en -3 par groupe heterocyclique, leur preparation et leur application en therapeutique
CN101119721A (zh) 雌激素受体-β选择性激动剂对放疗或化疗引起的粘膜炎和放射性膀胱炎的应用
HK1059895B (en) Use of pyridoindolone derivatives for preparing anticancer medicines
FR2868313A1 (fr) Nouvelle association entre un compose heterocyclique et un agent antioxydant et les compositions pharmaceutiques qui les contiennent
JPH03502806A (ja) ガンの処理
HK1060066B (en) Pharmaceutical combinations based on pyridoindolone derivatives and anticancer agents
WO2004032968A1 (fr) Association entre un compose heterocyclique favorisant les metabolismes glucidiques et lipidiques et un agent antioxydant dans le traitement de l'obesite

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 1200300903

Country of ref document: VN

Ref document number: P-834/03

Country of ref document: YU

AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2443012

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2003/07785

Country of ref document: ZA

Ref document number: 200307785

Country of ref document: ZA

Ref document number: 528671

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 158312

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 2002304551

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 10826002

Country of ref document: BG

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2002584919

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: PA/a/2003/009639

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: PV2003-2909

Country of ref document: CZ

WWE Wipo information: entry into national phase

Ref document number: 13252003

Country of ref document: SK

WWE Wipo information: entry into national phase

Ref document number: 10476322

Country of ref document: US

Ref document number: 028089596

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 2002732841

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2002732841

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: PV2003-2909

Country of ref document: CZ

WWP Wipo information: published in national office

Ref document number: 528671

Country of ref document: NZ

WWG Wipo information: grant in national office

Ref document number: 528671

Country of ref document: NZ

WWG Wipo information: grant in national office

Ref document number: PV2003-2909

Country of ref document: CZ

WWG Wipo information: grant in national office

Ref document number: 2002732841

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 2002304551

Country of ref document: AU