WO2000064898A1 - Derives d'azaindole destines au traitement de la depression - Google Patents

Derives d'azaindole destines au traitement de la depression Download PDF

Info

Publication number
WO2000064898A1
WO2000064898A1 PCT/US2000/010628 US0010628W WO0064898A1 WO 2000064898 A1 WO2000064898 A1 WO 2000064898A1 US 0010628 W US0010628 W US 0010628W WO 0064898 A1 WO0064898 A1 WO 0064898A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
pharmaceutically acceptable
ring
halogen
Prior art date
Application number
PCT/US2000/010628
Other languages
English (en)
Inventor
Richard Eric Mewshaw
Kristin Lynne Meagher
Original Assignee
American Home Products Corporation
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 American Home Products Corporation filed Critical American Home Products Corporation
Priority to JP2000614250A priority Critical patent/JP2002543079A/ja
Priority to EP00923540A priority patent/EP1171439A1/fr
Priority to CA002367681A priority patent/CA2367681A1/fr
Priority to BR0010693-3A priority patent/BR0010693A/pt
Priority to AU43644/00A priority patent/AU4364400A/en
Publication of WO2000064898A1 publication Critical patent/WO2000064898A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A61P25/24—Antidepressants

Definitions

  • This invention relates to compounds useful for the treatment of diseases affected by disorders of the serotonin- affected neurological systems, such as depression and anxiety. More specifically, the present invention is directed to aryl piperazinyl cyclohexyl derivatives useful for the treatment of such disorders.
  • SSRIs selective serotonin reuptake inhibitors
  • X is H, halo, C,-C 4 alkoxy, C,-C 4 alkylthio, C,-C 4 alkyl, benzyloxy, hydroxy or carbaxamido;
  • Y is O, S or a bond;
  • n is 1-4;
  • Ar is 1-naphthyl, 2-naphthyl, phenyl or phenyl, mono-substituted with a substituent selected from the group consisting of halo, C M alkoxy, C M alkylthio, C M benzyloxy hydroxy or trifluoromethyl.
  • U.S. Patent No. 5,627,196 discloses compounds of the following formula as having effects on serotonin-related systems.
  • D is a residue which combines with the carbon atoms to which it is attached to complete a pyrrolyl, imidazolyl, pyridinyl, pyrazinyl, pyridazinyl or pyrimidinyl group;
  • X is hydrogen, phenyl, hydroxy or methoxy provided that X is hydrogen or phenyl where r is 0;
  • R is -NH-R
  • A may be:
  • R, and R 2 form a carbocyclic or heterocyclic ring of 5 to 7 atoms, wherein said ring may be saturated or unsaturated ;
  • X is independently hydrogen, cyano, carbamoyl, halogen or alkoxy; or pharmaceutically acceptable salts thereof.
  • Preferred compounds of the present invention are preferably those of Formula I, wherein:
  • R, and R j form a carbocyclic or heterocyclic ring of 5-6 atoms; and X is hydrogen; or pharmaceutically acceptable salts thereof.
  • the compounds of the present invention are selected from the following:
  • alkoxy is meant to include both straight and branched carbon chains containing 1-6 carbon atoms.
  • halogen is meant to include fluorine, chlorine, bromine and iodine.
  • heterocyclic ring mean saturated or unsaturated rings containing one or more heteroatoms, preferably selected from oxygen, nitrogen and sulfur. Preferred examples contain, 5 or 6 atoms, particular examples, are 1,4-dioxane, pyrrole and pyridine.
  • carbocyclic ring means saturated or unsaturated carbon rings such as aryl or cycloalkyl, preferably containing 5 or 6 carbon atoms..
  • the compounds of Formula I also may be used in the form of a pharmaceutically acceptable acid addition salt having the utility of the free base.
  • Such salts prepared by methods well known to the art are formed with both inorganic or organic acids, for example: fumaric, maleic, benzoic, ascorbic, pamoic, succinic, bismethylenesalicylic, methanesulfonic, ethanedisulfonic, acetic, oxalic, propionic, tartaric, salicyclic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzene- sulfonic, hydrochloric hydrobromic, sulfuric, cyclohexylsulfamic, phosphoric and nitric acids.
  • the compounds of the present invention may be prepared by any suitable method which will be recognized by those skilled in the art. However, the present compounds may be advantageously prepared according to Scheme 1 set forth below.
  • the oxalate salt was prepared in ethanol: mp 202-205°C Elemental analysis for C 23 H 22 N 4 O » C 2 H 2 O 4 « 0.5H 2 O Calc'd: C, 72.80; H, 6.11; N, 14.77
  • the PCR cloning of the human 5-HT 1A receptor subtype from a human genomic library has been described previously by Chanda et al., Mol. Pharmacol.. 43:516 (1993).
  • a stable Chinese hamster ovary cell line expressing the human 5-HT 1A receptor subtype (5-HT IA .CHO cells) was employed throughout this study. Cells were maintained in DMEM supplemented with 10% fetal calf serum, non-essential amino acids and penicillin/ streptomycin.
  • Cells were grown to 95-100% confluency as a monolayer before membranes were harvested for binding studies. Cells were gently scraped from the culture plates, transferred to centrifuge tubes, and washed twice by centrifugation (2000 rpm for 10 min., 4°C) in buffer (50 mM Tris; pH 7.5). The resulting pellets were aliquoted and maintained at -80°C. On the day of assay, the cells were thawed on ice, and resuspended in buffer. Studies were conducted using [ 3 H]8-OH-DPAT as the radioligand. The binding assay was performed in 96 well microtiter plates in a final total volume of 250 ⁇ L of buffer.
  • frontal cortical membranes prepared from male Sprague-Dawley rats were incubated with 3 H-paroxetine (0.1 nM) for 60 min at 25°C. All tubes also contained either vehicle, test compound (one to eight concentrations), or a saturating concentration of fluoxetine (10 ⁇ M) to define specific binding. All reactions were terminated by the addition of ice cold Tris buffer followed by rapid filtration using a
  • 5-HT 1A cloned receptor membrane fragments (as used for 5-HT 1A receptor binding assays) were stored at -70°C. When needed, membranes were rapidly thawed, centrifuged at 40,000 x g for
  • the following assays were performed by incubating the cells with DMEM containing 25 mM HEPES, 5 mM theophylline and 10 ⁇ M pargyline for a period of 20 minutes at 37°C. Functional activity was assessed by treating the cells with forskolin (1 uM final concentration) followed immediately by test compound (6 concentrations) for an additional 10 min at 37°C. In separate experiments, 6 concentrations of antagonist were preincubated for 20 min prior to the addition of 10 nM 8-OH-DPAT and forskolin. The reaction was terminated by removal of the media and addition of 0.5 ml ice cold assay buffer. Plates were stored at -20°C prior to assessment of cAMP formation by a cAMP SPA assay (Amersham).
  • the compounds of the present invention are active towards 5HT 1A receptors and generally elevate serotonin levels by inhibiting 5-HT transport. Accordingly, the present compounds should be useful in treating disorders related to defects in serotonin concentration.
  • the compounds of formula I for use in methods of treatment or therapy form further aspects of the present invention.
  • the compounds of this invention may be administered orally or parenterally, neat or in combination with conventional pharmaceutical carriers.
  • Applicable solid carriers can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents or an encapsulating material.
  • the carrier is a finely divided solid which is in admixture with the finely divided active ingredient.
  • the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired.
  • the powders and tablets preferably contain up to 99% of the active ingredient. Any of the solid carriers known to those skilled in the art may be used with the compounds of this invention.
  • Particularly suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, low melting waxes and ion exchange resins.
  • Liquid carriers may be used in preparing solutions, suspensions, emulsions, syrups and elixirs of the compounds of this invention.
  • the compounds of this invention can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fat.
  • the liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators.
  • liquid carriers for oral and parenteral administration include water (particularly containing additives as above, e.g., cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g., glycols) and their derivatives and oils (e.g., fractionated coconut oil and arachis oil).
  • the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate.
  • Sterile liquid carriers are used in compositions for parenteral administration.
  • Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously.
  • Compositions for oral administration may be either liquid or solid composition form.
  • the pharmaceutical compositions containing the compounds of this invention are in unit dosage form, e.g., tablets or capsules.
  • the compositions may be sub-divided in unit doses containing appropriate quantities of the present compounds.
  • the unit dosage forms can be packaged compositions, for example, packeted powders, vials, ampoules, prefilled syringes or sachets containing liquids.
  • the unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form.
  • the therapeutically effective amount of the compounds of this invention that is administered and the dosage regimen depends on a variety of factors, including the weight, age, sex, and medical condition of the subject, the severity of the disease, the route and frequency of administration, and the specific compound employed, and thus may vary widely.
  • the pharmaceutical compositions may contain the compounds of this invention in the range of about 0.1 to about 2000 mg, preferably in the range of about 0.5 to about 500 mg and more preferably between about 1 and about 100 mg.
  • Projected daily dosages of active compound are about 0.01 to about 100 mg/kg body weight. The daily dose can be conveniently administered two to four times per day.
  • compositions comprising the compounds of formula I and a pharmaceutically acceptable carrier form a further aspect of the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne des composés utilisés dans le traitement de maladies en rapport avec les troubles des systèmes neurologiques liés à la sérotonine, tel que la dépression et l'anxiété. Ces composés sont représentés par la formule (I), dans laquelle R1 et R2 forment un noyau carbocyclique ou hétérocyclique de 5 à 7 atomes, ledit noyau pouvant être saturé ou non saturé ; X est indépendamment hydrogène, cyano, carbamoyl, halogène ou alcoxy, ou des sels pharmaceutiquement acceptables desdits composés.
PCT/US2000/010628 1999-04-22 2000-04-20 Derives d'azaindole destines au traitement de la depression WO2000064898A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2000614250A JP2002543079A (ja) 1999-04-22 2000-04-20 うつ病治療用のアザインドール誘導体
EP00923540A EP1171439A1 (fr) 1999-04-22 2000-04-20 Derives d'azaindole destines au traitement de la depression
CA002367681A CA2367681A1 (fr) 1999-04-22 2000-04-20 Derives d'azaindole destines au traitement de la depression
BR0010693-3A BR0010693A (pt) 1999-04-22 2000-04-20 Derivados azaindol para tratamento de depressão
AU43644/00A AU4364400A (en) 1999-04-22 2000-04-20 Azaindole derivatives for the treatment of depression

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US29673699A 1999-04-22 1999-04-22
US09/296,736 1999-04-22

Publications (1)

Publication Number Publication Date
WO2000064898A1 true WO2000064898A1 (fr) 2000-11-02

Family

ID=23143341

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/010628 WO2000064898A1 (fr) 1999-04-22 2000-04-20 Derives d'azaindole destines au traitement de la depression

Country Status (8)

Country Link
EP (1) EP1171439A1 (fr)
JP (1) JP2002543079A (fr)
CN (1) CN1348451A (fr)
AR (1) AR028475A1 (fr)
AU (1) AU4364400A (fr)
BR (1) BR0010693A (fr)
CA (1) CA2367681A1 (fr)
WO (1) WO2000064898A1 (fr)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7635696B2 (en) 2004-11-26 2009-12-22 Janssen Pharmaceutica N.V. Isoxazoline-indole derivatives with an improved antipsychotic and anxiolytic activity
US8865735B2 (en) 2011-02-21 2014-10-21 Hoffman-La Roche Inc. Solid forms of a pharmaceutically active substance
US8871774B2 (en) 2010-12-16 2014-10-28 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9051319B2 (en) 2011-08-01 2015-06-09 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9096593B2 (en) 2009-11-06 2015-08-04 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9150570B2 (en) 2012-05-31 2015-10-06 Plexxikon Inc. Synthesis of heterocyclic compounds
US9169250B2 (en) 2006-11-22 2015-10-27 Plexxikon Inc. Compounds modulating c-fms and/or c-kit activity and uses therefor
US9345708B2 (en) 2009-06-17 2016-05-24 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9447089B2 (en) 2009-04-03 2016-09-20 Plexxikon Inc. Compositions and uses thereof
US9469640B2 (en) 2007-07-17 2016-10-18 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9624213B2 (en) 2011-02-07 2017-04-18 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9771361B2 (en) 2013-11-13 2017-09-26 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US10023569B2 (en) 2013-11-13 2018-07-17 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication
US10273233B2 (en) 2015-05-13 2019-04-30 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US10533004B2 (en) 2015-05-13 2020-01-14 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005534619A (ja) * 2002-03-28 2005-11-17 エーザイ株式会社 Ｃ−ｊｕｎｎ−末端キナーゼ阻害剤としてのアザインドール

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0714894A1 (fr) * 1994-12-01 1996-06-05 Eli Lilly And Company 3-(1,2,3,6-Tétrahydro-(1-alkylénearyl)-4-pyridinyl)- et 3-(1-alkylenearyl)-4-pipéridinyl-1h-indoles: nouveaux agonistes 5-HT1f
EP0722941A2 (fr) * 1995-01-17 1996-07-24 Eli Lilly And Company Composés ayant des effets sur des systèmes apparentés à la sérotonine
US5627196A (en) * 1995-01-17 1997-05-06 Eli Lilly And Company Compounds having effects on serotonin-related systems

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0714894A1 (fr) * 1994-12-01 1996-06-05 Eli Lilly And Company 3-(1,2,3,6-Tétrahydro-(1-alkylénearyl)-4-pyridinyl)- et 3-(1-alkylenearyl)-4-pipéridinyl-1h-indoles: nouveaux agonistes 5-HT1f
EP0722941A2 (fr) * 1995-01-17 1996-07-24 Eli Lilly And Company Composés ayant des effets sur des systèmes apparentés à la sérotonine
US5627196A (en) * 1995-01-17 1997-05-06 Eli Lilly And Company Compounds having effects on serotonin-related systems

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7635696B2 (en) 2004-11-26 2009-12-22 Janssen Pharmaceutica N.V. Isoxazoline-indole derivatives with an improved antipsychotic and anxiolytic activity
US9487515B2 (en) 2006-11-22 2016-11-08 Plexxikon Inc. Compounds modulating c-fms and/or c-kit activity and uses therefor
US9169250B2 (en) 2006-11-22 2015-10-27 Plexxikon Inc. Compounds modulating c-fms and/or c-kit activity and uses therefor
US10426760B2 (en) 2007-07-17 2019-10-01 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9844539B2 (en) 2007-07-17 2017-12-19 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9469640B2 (en) 2007-07-17 2016-10-18 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9447089B2 (en) 2009-04-03 2016-09-20 Plexxikon Inc. Compositions and uses thereof
US9663517B2 (en) 2009-04-03 2017-05-30 Plexxikon Inc. Compositions and uses thereof
US9345708B2 (en) 2009-06-17 2016-05-24 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US10039762B2 (en) 2009-06-17 2018-08-07 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9518056B2 (en) 2009-06-17 2016-12-13 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US10874673B2 (en) 2009-06-17 2020-12-29 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9808459B2 (en) 2009-06-17 2017-11-07 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9096593B2 (en) 2009-11-06 2015-08-04 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US8871774B2 (en) 2010-12-16 2014-10-28 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US12076322B2 (en) 2011-02-07 2024-09-03 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9624213B2 (en) 2011-02-07 2017-04-18 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US11337976B2 (en) 2011-02-07 2022-05-24 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US8865735B2 (en) 2011-02-21 2014-10-21 Hoffman-La Roche Inc. Solid forms of a pharmaceutically active substance
US9908878B2 (en) 2011-08-01 2018-03-06 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9394302B2 (en) 2011-08-01 2016-07-19 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US10875855B2 (en) 2011-08-01 2020-12-29 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9051319B2 (en) 2011-08-01 2015-06-09 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US9695169B2 (en) 2012-05-31 2017-07-04 Plexxikon Inc. Synthesis of heterocyclic compounds
US9150570B2 (en) 2012-05-31 2015-10-06 Plexxikon Inc. Synthesis of heterocyclic compounds
US10023569B2 (en) 2013-11-13 2018-07-17 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication
US9771361B2 (en) 2013-11-13 2017-09-26 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US10640501B2 (en) 2013-11-13 2020-05-05 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication
US11345700B2 (en) 2013-11-13 2022-05-31 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication
US10273233B2 (en) 2015-05-13 2019-04-30 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US10533004B2 (en) 2015-05-13 2020-01-14 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication

Also Published As

Publication number Publication date
AU4364400A (en) 2000-11-10
JP2002543079A (ja) 2002-12-17
EP1171439A1 (fr) 2002-01-16
BR0010693A (pt) 2002-02-05
CN1348451A (zh) 2002-05-08
CA2367681A1 (fr) 2000-11-02
AR028475A1 (es) 2003-05-14

Similar Documents

Publication Publication Date Title
US5834493A (en) Indole derivatives as 5-HT1A and/or 5-HT2 ligands
EP1171439A1 (fr) Derives d'azaindole destines au traitement de la depression
WO2000040581A1 (fr) Derives de la 3,4-dihydro-2h benzo[1,4]oxazine
EP0464604A2 (fr) 1-Indolylalkyl-4-(alkoxypyrimidinyl)pipérazines
AU772978B2 (en) New benzenesulphonamide compounds, a process for their preparation and pharmaceutical compositions containing them
US6337336B1 (en) Azaindole derivatives for the treatment of depression
EP1070050A1 (fr) N-aryloxyethyl-indoly-alkylamines utilisees pour le traitement de la depression (principes actifs de recepteurs du type 5-ht1a)
EP1140925B1 (fr) 3,4-dihydro-2h-benzo 1,4]oxazinyl-methyl 3-(1h-indol-3-yl)-alkyl]-amines
US7332506B2 (en) Substituted-3-indolyl-4-piperidino-alkyl heterocycles for the treatment of depression
WO1999051592A1 (fr) Derives d'amine indol-3-yl-cyclhexyle utilises dans le traitement de la depression (antagonistes du recepteur 5-ht1)
EP1073651B1 (fr) Derives d'indolyle en tant qu'agents serotoninergiques
EP0765323B1 (fr) Derives de 4-(6-fluoro-1,2-benzisoxazolyl)-1-piperidinyl-propoxy-chromen-4-one, leur preparation et leur utilisation dans le traitement des psychoses, de la schizophrenie et de l'anxiete
EP1140919B1 (fr) Antidepresseurs a base de derives de cyclohexane 1,4-disubstitues pour le traitement des depressions
US6221863B1 (en) 3,4-dihydro-2H-benzo[1,4]oxazine derivatives
US6121307A (en) N-aryloxyethyl-indoly-alkylamines for the treatment of depression
US6162803A (en) Indol-3-yl-cyclohexyl amine derivatives for the treatment of depression
US6245780B1 (en) Tetrahydroisoquinolinyl-indole derivatives for the treatment of depression
MXPA01010677A (en) Azaindole derivatives for the treatment of depression
EP1068199B1 (fr) N-aryloxyethyle-indoly-alkylamines pour le traitement de la depression
US6150533A (en) N-aryloxyethyl-indoly-alkylamines for the treatment of depression
US6313114B1 (en) 3,4-Dihydro-2H-benzo[1,4]oxazinyl-methyl)-[3-(1H-indol-3yl)-alkyl]- amines
US6200994B1 (en) 1,4-Disubstituted cyclohexane derivatives for the treatment of depression
JPH02221274A (ja) 新規な誘導体類
US6337326B1 (en) N-aryl-(homopiperazinyl)-cyclohexyl amines
JP2687463B2 (ja) 縮合複素環化合物

Legal Events

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

Ref document number: 00806589.6

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ 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 NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG 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 BF BJ CF CG CI CM GA GN 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)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2000923540

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2000 614250

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2367681

Country of ref document: CA

Ref document number: 2367681

Country of ref document: CA

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: PA/a/2001/010677

Country of ref document: MX

WWP Wipo information: published in national office

Ref document number: 2000923540

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 2000923540

Country of ref document: EP