EP2167460A2 - Neuartige naphthalenderivate, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit - Google Patents

Neuartige naphthalenderivate, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit

Info

Publication number
EP2167460A2
EP2167460A2 EP08827457A EP08827457A EP2167460A2 EP 2167460 A2 EP2167460 A2 EP 2167460A2 EP 08827457 A EP08827457 A EP 08827457A EP 08827457 A EP08827457 A EP 08827457A EP 2167460 A2 EP2167460 A2 EP 2167460A2
Authority
EP
European Patent Office
Prior art keywords
formula
compound
branched
linear
pharmaceutically acceptable
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Withdrawn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
EP08827457A
Other languages
English (en)
French (fr)
Inventor
Saïd YOUS
Mohamed Ettaoussi
Ahmed Sabaouni
Pascal Berthelot
Michaël SPEDDING
Philippe Delagrange
Daniel-Henri Caignard
Mark Millan
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.)
Laboratoires Servier SAS
Original Assignee
Laboratoires Servier SAS
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 Laboratoires Servier SAS filed Critical Laboratoires Servier SAS
Publication of EP2167460A2 publication Critical patent/EP2167460A2/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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

Definitions

  • the present invention relates to novel naphthalenic derivatives, process for their preparation and pharmaceutical compositions containing them.
  • the compounds of the present invention are novel and have very interesting pharmacological characteristics concerning melatoninergic receptors.
  • melatonin N-acetyl-5-methoxytryptamine
  • melatonin analogues which are metabolically more stable and have an agonist or antagonist character, which can be expected to have a therapeutic effect greater than that of the hormone itself.
  • the melatoninergic system ligands possess interesting pharmacological properties on the central nervous system, including anxiolytics and antipsychotics
  • the present invention relates more particularly to the compounds of formula (I):
  • R 1 represents an alkyl (Ci-C 6) linear or branched, alkenyl (Ci-C 6) linear or branched haloalkyl (Ci-C 6) linear or branched polyhaloalkyl (Ci-C 6) linear or branched cycloalkyl (C 3 -C 8 ), cycloalkyl (C 3 -C 8 ) alkyl (C 1 -C 6 ), the alkyl portion may be linear or branched, aryl, aryl (C 1 -C 6 ) alkyl, the alkyl part may be linear or branched , heteroaryl or heteroarylalkyl (Ci-C 6 ) whose alkyl part may be linear or branched
  • aryl means a phenyl, naphthyl or biphenyl group
  • heteroaryl any mono or bicyclic aromatic group containing 1 to 3 heteroatoms chosen from oxygen, sulfur and nitrogen, the aryl and heteroaryl groups thus defined being capable of being substituted with 1 to 3 groups chosen from alkyl (C 1 -C 6) linear or branched alkoxy (C 1 -C 6) linear or branched, hydroxy, carboxy, formyl, nitro, cyano, halo (C 1 -C 6) linear or branched polyhaloalkyl (C 1 -C 6) -straight or branched, alkyloxycarbonyl, or halogen atoms,
  • hydrochloric hydrobromic, sulfuric, phosphonic, acetic, trifluoroacetic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, tartaric, maleic, citric, ascorbic, oxalic and methane acids. sulfonic, camphoric, etc.
  • pharmaceutically acceptable bases mention may be made, without limitation, of sodium hydroxide, potassium hydroxide, triethylamine, tertbutylamine, and the like.
  • the preferred compounds of the invention are the compounds of formula (I) for which R 1 represents a linear or branched (Ci-C 6 ) alkyl group such as, for example, the methyl group.
  • the group R 2 represents a hydrogen atom or a methyl group. - AT -
  • the invention also extends to the process for the preparation of the compound of formula (I), characterized in that the compound of formula (II) used is the starting material:
  • the pharmacological study of the derivatives of the invention has shown that they are atoxic, endowed with a high selective affinity for melatonin receptors and have important activities on the central nervous system and, in particular, have been noted.
  • therapeutic properties on sleep disorders, antidepressant, anxiolytic, antipsychotic, analgesic and microcirculation properties which make it possible to establish that the products of the invention are useful in the treatment of stress, sleep disorders, anxiety, seasonal depression or major depression, cardiovascular pathologies, pathologies of the digestive system, insomnia and fatigue due to jet lag, schizophrenia, panic attacks, melancholy, disorders of the appetite, obesity, insomnia, psychotic disorders, epilepsy, diabetes, Parkinson's disease, senile dementia, various disorders related to normal or pathological aging, migraine, memory loss, Alzheimer's disease, as well as disorders of the cerebral circulation.
  • the products of the invention can be used in malfunctions they possess the properties of ovulation inhibitors, immunomodulators and that they are likely to
  • the compounds will preferably be used in the treatment of major depression, seasonal depression, sleep disorders, cardiovascular pathologies, pathologies of the digestive system, insomnia and fatigue due to jet lag, appetite disorders and obesity.
  • the present invention also relates to pharmaceutical compositions containing at least one compound of formula (I) alone or in combination with one or more pharmaceutically acceptable excipients.
  • compositions according to the invention mention may be made, more particularly, of those which are suitable for oral, parenteral, nasal, percutaneous, rectal, perlingual, ocular or respiratory administration and in particular simple or coated tablets, sublingual tablets. , sachets, packets, capsules, glossettes, lozenges, suppositories, creams, ointments, dermal gels, and oral or injectable ampoules.
  • lithium aluminum hydride (37.1 mmol) is suspended in 200 ml of diethyl ether.
  • the compound obtained in Stage D (18.6 mmol), solubilized in 50 ml of tetrahydrofuran, is added dropwise.
  • the reaction medium is stirred at room temperature for 1 hour.
  • the excess lithium aluminum hydride is destroyed by successive additions of 1.4 ml of water, 1.4 ml of 15% sodium hydroxide and 4.2 ml of water.
  • the formed mineral precipitate is removed by filtration and washed with 50 ml of tetrahydrofuran.
  • the filtrate is dried over magnesium sulphate and evaporated under reduced pressure.
  • Step E The compound obtained in Step E (20 mmol) is dissolved in a water / ethyl acetate mixture (25 ml / 75 ml) cooled to 0 ° C. Potassium carbonate (60 mmol) is added and the acetyl chloride (26 mmol) is added dropwise to the reaction medium. The whole is stirred vigorously for 30 minutes at room temperature. The two phases are separated and the organic phase is washed with a 0.1M aqueous hydrochloric acid solution and then with water. After drying over magnesium sulphate, the organic phase is evaporated under reduced pressure. The resulting residue is recrystallized from acetonitrile to yield the title product as a white solid. Melting point: 173-175 ° C
  • Step G the compound obtained in Step G (4.2 mmol) is dissolved in 25 ml of methanol. Hydroxylamine hydrochloride (16.8 mmol) and pyridine (21.1 mmol) are added and the reaction mixture is refluxed with magnetic stirring for 3 hours. After cooling, the reaction medium is poured into 50 ml of water. The precipitate formed is drained, washed with water and recrystallized from toluene to yield the title product in the form of a white solid. Melting point: 136-138 ° C
  • Acute toxicity was assessed after oral administration to batches of 8 mice (26 ⁇ 2 grams). The animals were observed at regular intervals during the first day and daily for two weeks after treatment. The LD 50, resulting in the death of 50% of the animals, was evaluated and showed the low toxicity of the compounds of the invention.
  • the apparatus consists of a Plexiglas cylinder filled with water.
  • the animals are tested individually during a 6-minute session. At the beginning of each test, the animal is placed in the center of the cylinder. The downtime is recorded. Each animal is judged immobile when it ceases to struggle, and remains on the surface of the water, motionless, making only the movements allowing it to keep its head out of the water.
  • the compounds of the invention significantly reduce the duration of immobilization attesting to their antidepressant activity.
  • the MT 1 or MT 2 receptor binding experiments are carried out using the
  • the values of K; found for the compounds of the invention attest to a binding for one or the other melatoninergic binding sites, these values being ⁇ 10 .mu.M.
  • the compound obtained in Example 2 has a Ki (MT 1 ) of 7 nM and a K 1 (MT 2 ) of 0.8 nM.
  • One-month-old male rats are subjected to a light cycle of 12 hours of light per day as soon as they arrive at the laboratory (LD 12:12).
  • the rats receive a daily administration of the molecule to be tested.
  • the compounds of the invention are tested in a behavioral model, the light / dark cages test, which reveals the anxiolytic activity of the molecules.
  • the device consists of two polyvinyl boxes covered with Plexiglas. One of these boxes is obscure. One lamp is placed above the other box giving a luminous intensity in the center of it of approximately 4000 lux. An opaque plastic tunnel separates the clear box from the dark box. The animals are tested individually during a 5 min session. The floor of each box is cleaned between each session. At the beginning of each test, the mouse is placed in the tunnel, facing the dark box. The time spent by the mouse in the lighted box and the number of transitions through the tunnel are recorded after the first entry in the dark box. After administration of the compounds 30 min before the start of the test, the compounds of the invention significantly increase the time spent in the illuminated cage and the number of transitions, which shows the anxiolytic activity of the derivatives of the invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Immunology (AREA)
  • Psychiatry (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Pain & Pain Management (AREA)
  • Gynecology & Obstetrics (AREA)
  • Emergency Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Anesthesiology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pregnancy & Childbirth (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
EP08827457A 2007-07-02 2008-07-01 Neuartige naphthalenderivate, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit Withdrawn EP2167460A2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0704747A FR2918372B1 (fr) 2007-07-02 2007-07-02 Nouveaux derives naphtaleniques,leur procede de preparation et les compositions pharmaceutiques qui les contiennent
PCT/FR2008/000932 WO2009022063A2 (fr) 2007-07-02 2008-07-01 Nouveaux derives naphtaleniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Publications (1)

Publication Number Publication Date
EP2167460A2 true EP2167460A2 (de) 2010-03-31

Family

ID=38925714

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08827457A Withdrawn EP2167460A2 (de) 2007-07-02 2008-07-01 Neuartige naphthalenderivate, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit

Country Status (15)

Country Link
US (1) US7947852B2 (de)
EP (1) EP2167460A2 (de)
JP (1) JP2010531859A (de)
KR (1) KR20100029262A (de)
CN (1) CN101687777A (de)
AR (1) AR070005A1 (de)
AU (1) AU2008288373B2 (de)
BR (1) BRPI0814402A2 (de)
CA (1) CA2691586A1 (de)
EA (1) EA201000083A1 (de)
FR (1) FR2918372B1 (de)
MA (1) MA31577B1 (de)
UA (1) UA94828C2 (de)
WO (1) WO2009022063A2 (de)
ZA (1) ZA201000024B (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102603545B (zh) * 2012-02-10 2014-03-12 武汉万知生物医药有限公司 一种7-甲氧基-1-萘乙胺的制备方法
FR3014433B1 (fr) * 2013-12-05 2015-12-25 Servier Lab Nouveau procede de synthese du 7-methoxy-naphtalene-1-carbaldehyde et application a la synthese de l'agomelatine

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2689124A1 (fr) * 1992-03-27 1993-10-01 Adir Nouvelles naphtylalkylamines, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
FR2737220B1 (fr) 1995-07-24 1997-09-26 Adir Sequences nucleiques codant pour des recepteurs de la melatonine et leurs applications
FR2762598A1 (fr) * 1997-04-25 1998-10-30 Adir Nouveaux composes heterocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennnent
FR2771739B1 (fr) * 1997-11-28 2001-04-20 Adir Nouveaux composes naphtaleniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
JP3841628B2 (ja) * 1999-08-20 2006-11-01 武田薬品工業株式会社 経皮吸収剤
FR2890562B1 (fr) * 2005-09-09 2012-10-12 Servier Lab Utilisation de l'agomelatine pour l'obtention de medicaments destines au traitement des troubles du sommeil chez le patient deprime

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2009022063A2 *

Also Published As

Publication number Publication date
EA201000083A1 (ru) 2010-06-30
AU2008288373A1 (en) 2009-02-19
CN101687777A (zh) 2010-03-31
US20100168244A1 (en) 2010-07-01
FR2918372A1 (fr) 2009-01-09
US7947852B2 (en) 2011-05-24
WO2009022063A3 (fr) 2009-04-16
CA2691586A1 (fr) 2009-02-19
FR2918372B1 (fr) 2009-08-28
KR20100029262A (ko) 2010-03-16
WO2009022063A2 (fr) 2009-02-19
AU2008288373B2 (en) 2011-08-04
AR070005A1 (es) 2010-03-10
BRPI0814402A2 (pt) 2015-08-04
JP2010531859A (ja) 2010-09-30
MA31577B1 (fr) 2010-08-02
ZA201000024B (en) 2011-04-28
UA94828C2 (ru) 2011-06-10

Similar Documents

Publication Publication Date Title
WO2008000969A1 (fr) Nouveaux derives naphtaleniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP2079689A2 (de) Neuartige indolderivate, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit
EP1873140B1 (de) Neue Naphtalinderivate, ihr Herstellungsverfahren und die pharmazeutischen Zusammensetzungen, die sie enthalten
EP0994102B1 (de) Zyklische Derivate mit einer zykloalkylenischen Kette, Verfahren zu ihrer Herstellung und pharmazeutische Zusammensetzungen die diese enthalten
EP1466604B1 (de) Isochinolinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung um Melatonin System-Probleme zu behandeln
WO2006027474A2 (fr) Nouveaux derives d ' imidazopyridine presentant une affinite vis a vis des recepteurs de la melatonine , leur procede de preparation et les compositions pharmaceutiques qui les contiennet
EP2167460A2 (de) Neuartige naphthalenderivate, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit
EP2167457A2 (de) Neuartige naphthalenderivate, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit
EP2086933A2 (de) Neuartige indolderivate, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit
CA2593618C (fr) Derives naphtaleniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2009022066A2 (fr) Nouveaux derives naphtaleniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2009022062A1 (fr) Nouveaux derives naphtaleniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2005012282A1 (fr) Nouveaux derives du benzothiofene 2-thiosubstitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2009022065A2 (fr) Nouveaux derives naphtaleniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP1106608A1 (de) Substituierte (Dihydro)benzoxazin- und (Dihydro)benzothiazinderivate, Verfahren zu deren Herstellung und sie enthaltende pharmazeutische Zusammensetzungen
WO2005012229A1 (fr) Nouveaux derives bicycliques alkyles, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2010061074A1 (fr) Derives indoles, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2004043907A1 (fr) Nouveaux derives du phenylnaphtalene, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20091216

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

GRAJ Information related to disapproval of communication of intention to grant by the applicant or resumption of examination proceedings by the epo deleted

Free format text: ORIGINAL CODE: EPIDOSDIGR1

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20130201