WO2003080050A1 - Utilisation de 3-[1-[2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]-6-chloro-1h-indole ou de ses enantiomeres pour le traitement de maladies et de troubles sensibles a l'inhibition du recaptage de 5-ht (serotonine) - Google Patents

Utilisation de 3-[1-[2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]-6-chloro-1h-indole ou de ses enantiomeres pour le traitement de maladies et de troubles sensibles a l'inhibition du recaptage de 5-ht (serotonine) Download PDF

Info

Publication number
WO2003080050A1
WO2003080050A1 PCT/DK2003/000210 DK0300210W WO03080050A1 WO 2003080050 A1 WO2003080050 A1 WO 2003080050A1 DK 0300210 W DK0300210 W DK 0300210W WO 03080050 A1 WO03080050 A1 WO 03080050A1
Authority
WO
WIPO (PCT)
Prior art keywords
dihydro
disorders
disorder
indol
indole
Prior art date
Application number
PCT/DK2003/000210
Other languages
English (en)
Inventor
Benny Bang-Andersen
Klaus Peter Hertel
Jørn ARNT
Original Assignee
H. Lundbeck A/S
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 H. Lundbeck A/S filed Critical H. Lundbeck A/S
Priority to AU2003215529A priority Critical patent/AU2003215529A1/en
Publication of WO2003080050A1 publication Critical patent/WO2003080050A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence

Definitions

  • the present invention relates to the use of 3-[l-[2-(l-acetyl ⁇ 2,3 ⁇ dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole, its enantiomers and pharmaceutically acceptable salts thereof for the preparation of medicaments useful for the treatment of diseases or disorders responsive to 5- ⁇ T (serotonin) re-uptake inhibition.
  • 5-HT re-uptake inhibitors are useful for the treatment of depression, anxiety disorders and other affective disorders, including generalised anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
  • 5-HT re-uptake inhibitors are effective in the treatment of dysthymic disorder (Thase et al. Arch Gen Psychiatry 1996, 53, 777-784).
  • 5-HT re-uptake inhibitors are also useful in the treatment of anxiety disorders. Clinical studies have shown that 5-HT re-uptake inhibitors have beneficial effects in generalized anxiety disorder (see e.g. Rocca et al. Ada Psychiatr Scand 1997, 95, 444-450). It is also well accepted that 5-HT re-uptake inhibitors are effective against panic anxiety/panic disorder (see e.g. Sheehan and Harnett-Sheehan J Clin Psychiatry 1996, 10, 51-58).
  • 5-HT re-uptake inhibitors appear also effective in the treatment of impulse control disorders (Durst et al. CNS Drugs 2001, 15, 185-195; Hollander et al. Psychiatr Clin North Am 2000, 23, 629-642; Christenson and Crow J Clin Psychiatry 1996, Suppl 8, 42-47).
  • 5-HT re-uptake inhibition may reduce aggression, probably due to positive effects on the serotonergic dysfunction that is implicated in aggressive behaviour directed towards oneself or others (for review see Walsh & Dinan Acta Psychiatr Scand 2001, 104, 84-91).
  • 5-HT re-uptake inhibitors are effective in the treatment of premenstrual syndrom (see e.g. Eriksson et al. Neuropsychopharmacology 1995, 12, 167-176).
  • 5-HT re-uptake inhibitors may also be useful in treatment of alcohol abuse (see Sellers et al. J Clin Psychiatry 1991, 52, 49-54). Therefor, 5-HT re- uptake inhibitors may be beneficial in the treatment of drug abuse.
  • 5-HT re-uptake inhibitors have been demonstrated to be effective in the treatment of both bulimia nervosa as well as in anorexia nervosa (see Kaye et al. Biol Psychiatry 1998, 44, 825-838). Clinical studies have indicated that treatment with 5-HT re-uptake inhibitors show superiority over placebo in reducing the frequency of binge eating episodes (Goldstein et al. Br J Psychiatry 1995, 166, 660-666). Moreover, published data suggest that 5-HT re-uptake inhibitors improves outcome and prevents relapse in people with anorexia nervosa (Kaye et al. Biol Psychiatry 1998, 44, 825-838). Thus, it seems clear that 5-HT re-uptake inhibitors are useful in the pharmacotherapy of eating disorders including bulimia and anorexia.
  • WO 98/28293 describes a series of substituted indane or dihydroindole compounds having effect at dopamine D 4 receptors. The compounds described are considered useful for the treatment of a range of psychiatric and neurological disorders, including the positive and negative symptoms of schizophrenia and other psychoses.
  • potent dopamine D 4 ligand may be particularly useful for the treatment of disorders responsive to inhibition of 5- ⁇ T re-uptake.
  • the present invention relates to the use of 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole having the formula (I), any of its enantiomers or pharmaceutically acceptable salts thereof for the treatment of diseases or disorders responsive to inhibition of 5- ⁇ T re-uptake.
  • the invention relates to the use of (S)-(+)-3-[l-[2-(l-acetyl-2,3-dihydro-lH- indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole or pharmaceutically acceptable salts thereof for the treatment of diseases or disorders responsive to inhibition of 5- ⁇ T re-uptake.
  • the present invention also relates to the use of 3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole having formula (I), or any of its enantiomers, but in particular (S)-(+)-3-[l-[2-(l-acetyl-2,3-dihydro-lH-indol-3- yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole, or pharmaceutically acceptable salts thereof for the preparation of a pharmaceutical composition for the treatment of diseases or disorders responsive to inhibition of 5- ⁇ T re-uptake.
  • Diseases and disorders responsive to inhibition of 5-HT re-uptake are depression, anxiety disorders and other affective disorders, including generalised anxiety disorder, panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder, eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
  • generalised anxiety disorder panic anxiety, obsessive compulsive disorder, acute stress disorder, post traumatic stress disorder or social anxiety disorder
  • eating disorders such as bulimia, anorexia and obesity, phobias, dysthymia, premenstrual syndrome, cognitive disorders, impulse control disorders including aggression and drug abuse.
  • the disease to be treated according with the invention is depression.
  • the compound 3-[l-[2-(l-acetyl-2,3-dihydro- lH-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-lH-indole and its enantio- mers are very potent 5- ⁇ T re-uptake inhibitors.
  • the 5-HT re-uptake inhibiting effect of this compound and its enantiomers is equipotent with the well-known antidepressant drugs citalopram and fluoxetine.
  • the present invention covers the use of both the racemate of the compound of formula (I) and each of its enantiomers for the treatment of diseases or disorders responsive to 5- HT re-uptake inhibition.
  • the compound of formula (I) and its enantiomers and pharmaceutically acceptable salts thereof may be prepared as described in WO 98/28293, see in particular examples 20 and 34.
  • the pharmaceutical formulations of the invention may be prepared by conventional methods in the art.
  • tablets may be prepared by mixing the active ingredient with ordinary adjuvants and/or diluents and subsequently compressing the mixture in a conventional tabletting machine.
  • adjuvants or diluents comprise: corn starch, potato starch, talcum, magnesium stearate, gelatine, lactose, gums, and the like. Any other adjuvants or additives usually used for such purposes such as colourings, flavourings, preservatives etc. may be used provided that they are compatible with the active ingredients.
  • Solutions for injections may be prepared by dissolving the active ingredient and possible additives in a part of the solvent for injection, preferably sterile water, adjusting the solution to desired volume, sterilising the solution and filling it in suitable ampules or vials. Any suitable additive conventionally used in the art may be added, such as tonicity agents, preservatives, antioxidants, etc.

Landscapes

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

Abstract

L'invention concerne l'utilisation de 3-[1-[2-(1-acétyl-2,3-dihydro-1H-indol-3-yl)éthyl]-3,6-dihydro-2H-pyridin-4-yl]-6-chloro-1H-indole, de l'un quelconque de ses énantiomères ou de sels pharmaceutiquement acceptables dudit composé pour la préparation d'une composition pharmaceutique destinée au traitement de maladies et de troubles sensibles à l'inhibition du recaptage de 5-HT.
PCT/DK2003/000210 2002-03-27 2003-03-26 Utilisation de 3-[1-[2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]-6-chloro-1h-indole ou de ses enantiomeres pour le traitement de maladies et de troubles sensibles a l'inhibition du recaptage de 5-ht (serotonine) WO2003080050A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003215529A AU2003215529A1 (en) 2002-03-27 2003-03-26 The use of 3-(1-(2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl)-3,6-dihydro-2h-pyridin-4-yl)-6-chloro-1h-indole or its enantiomers for the treatment of diseases and disorders responsive to 5-ht (serotonin) re-uptake inhibition

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US36843602P 2002-03-27 2002-03-27
DKPA200200479 2002-03-27
US60/368,436 2002-03-27
DKPA200200479 2002-03-27

Publications (1)

Publication Number Publication Date
WO2003080050A1 true WO2003080050A1 (fr) 2003-10-02

Family

ID=28455829

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK2003/000210 WO2003080050A1 (fr) 2002-03-27 2003-03-26 Utilisation de 3-[1-[2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]-6-chloro-1h-indole ou de ses enantiomeres pour le traitement de maladies et de troubles sensibles a l'inhibition du recaptage de 5-ht (serotonine)

Country Status (2)

Country Link
AU (1) AU2003215529A1 (fr)
WO (1) WO2003080050A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998028293A1 (fr) * 1996-12-20 1998-07-02 H.Lundbeck A/S Derives d'indane ou de dihydroindole

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998028293A1 (fr) * 1996-12-20 1998-07-02 H.Lundbeck A/S Derives d'indane ou de dihydroindole

Also Published As

Publication number Publication date
AU2003215529A1 (en) 2003-10-08

Similar Documents

Publication Publication Date Title
US5708035A (en) Methods of use and compositions of R(-) fluoxetine
KR101185322B1 (ko) 약제 제조용 밀나시프란의 (1에스,2알) 거울상이성체의용도
ES2670568T3 (es) 8-cloro-1-metil-2,3,4,5-tetrahidro-1H-3-benzacepina, sus sales, solvatos o hidratos y su uso para el tratamiento de trastornos del SNC
ES2273764T3 (es) Nuevos tratamientos que utilizan derivados de fenetilamina.
US20070053976A1 (en) Novel combination of drugs as antidepressant
JP7245509B2 (ja) 吃音を治療するための融合ベンズアゼピン
JP5491475B2 (ja) ムスカリン性受容体ｍ１拮抗剤を使用する精神状態の処置
NZ575218A (en) Use of the enantiomer (1S,2R) of milnacipran for the preparation of a medicament
AU1915192A (en) Method of treating/preventing substance abuse using 1-alkyl-5(substituted oxy)-2-aminotetralins
HUE034155T2 (en) Therapeutic uses of 1- [2- (2,4-dimethylphenylsulfanyl) phenyl] piperazine
KR100682291B1 (ko) 수면 무호흡증 치료용 약제학적 조성물
WO2003080050A1 (fr) Utilisation de 3-[1-[2-(1-acetyl-2,3-dihydro-1h-indol-3-yl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]-6-chloro-1h-indole ou de ses enantiomeres pour le traitement de maladies et de troubles sensibles a l'inhibition du recaptage de 5-ht (serotonine)
WO2004020437A1 (fr) S-(+)-3-{1-[2-(2,3-dihydro-1h-indol-3-yl)ethyl]-3,6-dihydro-2h-pyridin-4-yl}-6-chloro-1h-indole et sels d'addition d'acide de ce dernier
EP1942891B1 (fr) Nouvelle combinaison de medicaments utilises comme antidepresseur
US6552087B1 (en) Therapeutic agent comprising (+)-sibutramine
WO1992013452A1 (fr) Procedes d'utilisation et compositions de r(-) fluoxetine
JPH05506642A (ja) 薬物及びその使用
KR20010099648A (ko) 신규 조성물
EP1299120A2 (fr) Compositions pharmaceutiques renfermant un inhibiteur du transporteur de la serotonine et utilisation de celles-ci
WO2008017753A2 (fr) Composition pharmaceutique contenant en association le saredutant et un inhibiteur selectif de la recapture de la serotonine ou un inhibiteur de la recapture de la serotonine/norepinephrine
US4141993A (en) Compounds of diphenylcyclopentylamine type and methods for their preparation
AU6378299A (en) A new composition
AU2005215790A1 (en) Treatment or prophylaxis of migraine or headache disorders using citalopram, escitalopram or citalopram metabolites
Feighner Clinical overview of serotonin re-uptake inhibitors
CA2342223A1 (fr) Nouvelle composition

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

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 NI NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

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 BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK 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
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP