WO2003101440A1 - Metabolite de 1-dimethylamino-3-(3-methoxy-phenyle)-2-methyle-pentane-3-ole et son utilisation pour traiter l'enuresie - Google Patents

Metabolite de 1-dimethylamino-3-(3-methoxy-phenyle)-2-methyle-pentane-3-ole et son utilisation pour traiter l'enuresie Download PDF

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Publication number
WO2003101440A1
WO2003101440A1 PCT/EP2003/005490 EP0305490W WO03101440A1 WO 2003101440 A1 WO2003101440 A1 WO 2003101440A1 EP 0305490 W EP0305490 W EP 0305490W WO 03101440 A1 WO03101440 A1 WO 03101440A1
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Prior art keywords
dimethylamino
stereoisomers
salts
methyl
alkyl
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PCT/EP2003/005490
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German (de)
English (en)
Inventor
Burkhard Kurth
Jörg Holenz
Helmut Buschmann
Oswald Zimmer
Thomas Christoph
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Grünenthal GmbH
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Priority to EP03732465A priority Critical patent/EP1507521A1/fr
Priority to AU2003238398A priority patent/AU2003238398A1/en
Publication of WO2003101440A1 publication Critical patent/WO2003101440A1/fr
Priority to US10/999,219 priority patent/US20050137145A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/68—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C215/72—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with quaternised amino groups bound to the carbon skeleton
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C215/56—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups
    • C07C215/58—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups with hydroxy groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
    • C07C215/62—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups with hydroxy groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain the chain having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/64—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms
    • C07C217/66—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain
    • C07C217/72—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring

Definitions

  • the invention relates to metabolites of 1-dimethylamino-3- (3-methoxyphenyl) -2-methylpentan-3-ol as free bases and / or in the form of physiologically acceptable salts, their use for the preparation of a medicament for the treatment of Increased urinary urgency or urinary incontinence as well as corresponding drugs and methods for the treatment of increased urinary urgency or urinary incontinence.
  • Urinary incontinence is the involuntary discharge of urine. This occurs uncontrollably when the pressure within the bladder exceeds the pressure necessary to close the ureter. Causes may be an increased internal bladder pressure (eg due to detrusor instability) with the consequence of urge incontinence and a reduced sphincter pressure (eg after birth or surgical interventions) with the consequence of stress incontinence.
  • the detrusor is the roughly bundled multilayer bladder wall musculature, whose contraction leads to urination, the sphincter of the sphincter of the urethra.
  • Urinary urgency is the urinary voiding (micturition) condition of increased bladder muscle tension as it approaches 30 (or beyond) bladder capacity. This tension acts as a micronutrient.
  • urinary urgency By an increased urinary urgency one understands in particular the occurrence of premature or heaped sometimes even painful urinary urgency up to the so-called Urnzwang. This leads to a much more frequent micturition.
  • Causes may include bladder infections and neurogenic bladder disorders as well as bladder tuberculosis. But not all causes have been resolved.
  • drugs that increase urethral or bladder neck resistance in particular show affinities for ⁇ -adrenoreceptors such as ephedrine, ⁇ -adrenoreceptors such as clenbutarol, or hormones such as estradiol.
  • ⁇ -adrenoreceptors such as ephedrine, ⁇ -adrenoreceptors such as clenbutarol, or hormones such as estradiol.
  • Certain opioids, diarylmethylpiperazines and -piperidines are described for this indication in WO 93/15062.
  • the object of the present invention was therefore to find substances which are helpful for the treatment of increased urinary urgency or urinary incontinence and at the effective doses preferably at the same time show fewer side effects and / or analgesic effects than known from the prior art.
  • the compounds used are present as R, R, preferably 2R, 3R stereoisomers.
  • the compounds mentioned can also be used for the preparation of medicaments for the treatment of pain.
  • C 1 -C 2 -alkyl is C 1 -C 2 -alkyl
  • C 1 -C 3 -alkyl is C 1 -, C 2 - or C-3-alkyl
  • C 1 -C 4 -alkyl is C 1 -, C 2 -, C 3 - or C 4 -alkyl
  • 6 alkyl for C1, C2, C3, C4, C5 or C6 alkyl, d. 7 alkyl for C1-, C2-, C3-, C4-, C5-, C6- or C7-alkyl, ds-alkyl for C1-, C2-, C3-, C4-, C5-, C6-, C7- or C8-alkyl, Ci-io-alkyl for C1, C2, C3, C4, C5, C6, C7, C8, C9 or C10 alkyl and -C.
  • C 3 . 4 - cycloalkyl means C3- or C4-cycloalkyl, C. 3 5 for -cycloalkyl C3-, C4- or C5-cycloalkyl, C. 3 For 6 -cycloalkyl C3-, C4-, C5- or C6-cycloalkyl, C3-7- cycloalkyl is C3, C4, C5, C6 or C7 -cycloalkyl, C.
  • cycloalkyl In relation on cycloalkyl, the term also includes saturated cycloalkyls in which one or two carbon atoms are replaced by a heteroatom, S, N or O.
  • cycloalkyl also includes, in particular, mono- or polysubstituted, preferably monounsaturated, unsaturated cycloalkyls without a heteroatom in the ring, as long as the cycloalkyl is not an aromatic system.
  • the alkyl or cycloalkyl radicals are methyl, ethyl, vinyl (ethenyl), propyl, allyl (2-propenyl), 1-propynyl, methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl , Pentyl, 1, 1-dimethylpropyl, 1, 2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1-methylpentyl, cyclopropyl, 2-methylcyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cycloheptyl, cyclooctyl, but also adamantyl, CHF2, CF3 or CH2OH as well
  • Particularly preferred substituents here are F, Cl and OH.
  • the hydrogen radical can also be replaced by OC ⁇ - 3 alkyl or -C.
  • 3- alkyl each mono- or polysubstituted or unsubstituted, in particular methyl, ethyl, n-propyl, i-propyl, CF 3 , methoxy or ethoxy, be replaced.
  • (CH 2 ) 3 . 6 is -CH 2 -CH 2 -CH 2 -, -CH 2 -CH 2 -CH 2, -CH 2 - CH 2 -CH 2 -CH 2 and CH 2 -CH 2 -CH 2 -CH 2 -CH 2 - to understand under (CH 2 ) ⁇ - is -CH 2 -, -CH 2 -CH 2 -, -CH 2 -CH 2 -CH 2 - and -CH 2 -CH 2 -CH 2 -CH 2 - too understand, under (CH 2 ) 4 . 5 is -CH2-CH2-CH2-CH2- and -CH 2 -CH 2 -CH 2 -CH 2 - to be understood, etc. - CH 2
  • aryl radical is understood as meaning ring systems having at least one aromatic ring but without heteroatoms in even only one of the rings. Examples are phenyl, naphthyl, fluoranthenyl, fluorenyl, tetralinyl or indanyl, in particular 9H-fluorenyl or anthracenyl radicals, which may be unsubstituted or monosubstituted or polysubstituted.
  • a heteroaryl radical is understood as meaning heterocyclic ring systems having at least one unsaturated ring which contain one or more heteroatoms from the group consisting of nitrogen, oxygen and / or sulfur and may also be monosubstituted or polysubstituted.
  • Exemplary are from the group of heteroaryls furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, benzo [1, 2.5] thiadiazole, benzothiazole, indole, benzotriazole, benzodioxolane, benzodioxane, carbazole , Indole and quinazoline.
  • Substituted substitution of the aryl or heteroaryl with R 22 , OR 22 is a halogen, preferably F and / or Cl, a CF 3, a CN, a NO 2, in connection with aryl and heteroaryl.
  • NR 2 ⁇ R 24 a C-ug-alkyl (saturated), a C j .g-alkoxy, a C .g-Cycloalkoxy, a C 3-8 -cycloalkyl or a
  • the rest R 22 is H, one preferably a C j .g-alkyl, an aryl or heteroaryl or a via C j . Alkyl, saturated or unsaturated, or a C j . -Alkylene group bonded Aryl or heteroaryl radical, where these aryl and heteroaryl radicals may not themselves be substituted by aryl or heteroaryl radicals,
  • radicals R 23 and R 24 are identical or different, for H, a C 1-6 -alkyl, preferably a C- ⁇ g-alkyl, an aryl, a heteroaryl or a via bonded aryl or heteroaryl radical, these aryl and heteroaryl radicals may not themselves be substituted by aryl or heteroaryl radicals,
  • radicals R 23 and R 24 together are CH 2 CH 2 OCH 2 CH 2
  • R ⁇ 2 is H, a C j, preferably a C- ⁇ ß-alkyl, an aryl or heteroaryl radical or an about C-iQ-alkyl -.
  • ⁇ - alkyl saturated or unsaturated, or a C 1-8 alkylene group bonded aryl or
  • Heteroaryl radical where these aryl and heteroaryl radicals may not themselves be substituted by aryl or heteroaryl radicals.
  • physiologically acceptable salts especially physiologically acceptable salts with cations or bases and physiologically acceptable salts with anions or acids or else a salt formed with a physiologically acceptable acid or a physiologically acceptable cation.
  • physiologically acceptable salt with anions or acids is understood as meaning salts of at least one of the compounds according to the invention-usually, for example, nitrogen-protonated-as a cation having at least one anion which is physiologically-in particular when used in humans and / or Mammal - are compatible.
  • a physiologically acceptable acid namely salts of the respective active ingredient with inorganic or organic acids, which are physiologically compatible - in particular when used in humans and / or mammals.
  • physiologically tolerated salts of certain acids are salts of: hydrochloric, hydrobromic, sulfuric, methanesulfonic, formic, acetic, oxalic, succinic, malic, tartaric, mandelic, fumaric, lactic, citric, glutamic, 1, 1-dioxo-1,2 -dihydro1 b6-benzo [d] isothiazol-3-one (saccharic acid), monomethyl sebacic acid, 5-oxo-proline, hexane-1-sulfonic acid, nicotinic acid, 2-, 3- or 4-aminobenzoic acid, 2,4,6-trimethyl benzoic acid, ⁇ -lipoic acid, acetylglycine, acetylsalicylic acid, hippuric acid and / or aspartic acid.
  • Particularly preferred is the hydrochloride salt.
  • the term salt formed with a physiologically acceptable acid means salts of the respective active ingredient with inorganic or organic acids which are physiologically compatible, in particular when used in humans and / or mammals.
  • Particularly preferred is the hydrochloride.
  • physiologically acceptable acids are: hydrochloric, hydrobromic, sulfuric, methanesulfonic, formic, acetic, oxalic, succinic, tartaric, mandelic, fumaric, lactic, citric, glutamic, 1,1-dioxo-1, 2 dihydrol ⁇ 6 -benzo [d] isothiazol-3-one (saccharic acid), monomethyl sebacic acid, 5-oxoproline, hexane-1-sulphonic acid, nicotinic acid, 2-, 3- or 4-aminobenzoic acid, 2,4,6-trimethyl benzoic acid, ⁇ -lipoic acid, acetylglycine, acetylsalicylic acid,
  • physiologically compatible salt with cations or bases refers to salts of at least one of the compounds according to the invention-usually a (deprotonated) acid-as an anion having at least one, preferably inorganic, cation which is physiologically-in particular when used in humans and / or mammalian.
  • Particularly preferred are the salts of the alkali and alkaline earth metals but also with NH 4 ⁇ in particular but (mono-) or (di) sodium, (mono-) or (di) potassium, magnesium or calcium salts.
  • the term salt formed with a physiologically compatible cation means salts of at least one of the respective compounds as anion with at least one inorganic cation which is physiologically compatible, in particular when used in humans and / or mammals.
  • the salts of the alkali metals and alkaline earth metals are also particularly preferably NH 4 + , but in particular (mono-) or (di) sodium, (mono-) or (di) potassium, magnesium or calcium salts.
  • Another object of the invention are metabolites of 1-
  • metabolites of the invention are present as R, R, preferably 2R, 3R stereoisomers.
  • the metabolites according to the invention are physiologically harmless. Therefore, a further subject of the invention is a medicament, preferably for the treatment of increased urinary urgency or urinary incontinence, containing as active ingredient at least one compound selected from (2RS, 3RS) -1-dimethylamino-3- (3-methoxyphenyl) -2- Methyl-pentan-3-ol, (+) - (2R, 3R) -1-Dimethylamino-3- (3-methoxyphenyl) -2-methylpentan-3-ol, (-) - (2S, 3S ) -1-Dimethylamino-3- (3-methoxyphenyl) -2-methyl-pentan-3-ol, (2RS, 3RS) -3- (3-dimethylamino-1-ethyl-1-hydroxy-2-methyl -propyl) -phenol, (+)
  • the compounds present are present as R, R, preferably 2R, 3R stereoisomers.
  • Suitable additives and / or auxiliaries for the purposes of this invention are all substances known to the person skilled in the art from the prior art for achieving galenic formulations.
  • the choice of these excipients and the amounts to be used depend on whether the drug is to be administered orally, intravenously, intraperitoneally, intradermally, intramuscularly, intranasally, buccally or locally.
  • preparations in the form of tablets, chewable tablets, dragees, capsules, granules, drops, juices or syrups are suitable, for parenteral, topical and inhalative administration solutions, suspensions, readily reconstitutable dry preparations and sprays. Another possibility is suppositories for use in the rectum.
  • auxiliaries and admixtures for the oral administration forms are disintegrants, lubricants, binders, fillers, mold release agents, optionally solvents, flavorings, sugars, in particular vehicles, diluents, dyes, antioxidants, etc.
  • suppositories may include waxes or fatty acid esters and for parenteral application agents Carriers, preservatives, suspension aids, etc. may be used.
  • the amounts of active substance to be administered to patients vary depending on the weight of the patient, the mode of administration and the severity of the disease.
  • the compounds according to the invention can be released with a delay.
  • sustained-release formulations in particular in the form of a "once-daily" preparation, which must be taken only once a day, are particularly preferred.
  • drugs containing at least 0.05 to 90.0% of the active ingredient in particular low effective dosages, to avoid side effects or analgesic effects.
  • 0.1 to 5000 mg / kg, in particular 1 to 500 mg / kg, preferably 2 to 250 mg / kg body weight of at least one of the compounds according to the invention or used according to the invention are applied.
  • 0.01-5 mg / kg, preferably 0.03-2 mg / kg, in particular 0.05-1 mg / kg of body weight is also preferred and usual.
  • Excipients may be, for example: water, ethanol, 2-propanol, glycerol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, glucose, fructose, lactose, sucrose, dextrose, molasses, starch, modified starch, gelatin, sorbitol, inositol, mannitol, microcrystalline cellulose , Methylcellulose, carboxymethylcellulose,
  • compositions of the present invention are accomplished by means well known in the art of pharmaceutical formulation, devices, methods and methods as described, for example, in "Remington s Pharmaceutical Sciences", ed. A.R. Gennaro, 17th Ed., Mack Publishing Company, Easton, Pa. (1985), especially in Part 8, Chapters 76 to 93.
  • a solid formulation such as a tablet
  • the active ingredient of the drug ie a compound of the invention or used according to the invention or one of its pharmaceutically acceptable salts
  • a pharmaceutical carrier for example conventional tablet ingredients, such as corn starch, lactose, sucrose, sorbitol, Talc, magnesium stearate, dicalcium phosphate or pharmaceutically acceptable gums, and pharmaceutical diluents, such as water, to form a solid composition containing a compound of the invention or a pharmaceutically acceptable salt thereof in a homogeneous distribution.
  • a homogeneous distribution is understood here to mean that the active ingredient is distributed uniformly over the entire composition so that it can readily be absorbed into the composition equally effective unit dose forms, such as tablets, pills or capsules can be divided.
  • the solid composition is then subdivided into unit dose forms.
  • the tablets or pills of the drug or compositions of the invention may also be coated or otherwise compounded to provide a sustained release dosage form.
  • Suitable coating agents include polymeric acids and mixtures of polymeric acids with materials such as shellac, cetyl alcohol and / or cellulose acetate.
  • the medicaments according to the invention show only slight side effects, it may be advantageous, for example, to avoid certain forms of dependence, in addition to the compounds according to general formula I also morphine antagonists, in particular naloxone, naltrexone and / or levallorphan to use.
  • morphine antagonists in particular naloxone, naltrexone and / or levallorphan to use.
  • the invention also relates to a method for the treatment of increased urinary urgency or urinary incontinence, in which the compounds used in the invention are used.
  • Method A For the production of is first in a modification of the synthesis in Example 1 of DE 44 26 245 and US 6,248,737 instead of 1-dimethylamino-2-methyl-pentan-3-one 1- Methyl 1-benzylamino-2-methyl-pentan-3-one used. This can be purchased or out
  • Method B For the production of is first used in a modification of the synthesis in Example 1 of DE 44 26 245 or US 6,248,737 instead of 1-dimethylamino-2-methyl-pentane-3-one 1- dibenzylamino-2-methyl-pentan-3-one. This can be purchased or out
  • Method D First, according to DE 44 26 245 and US 6,248,737 3- (3-dimethylamino-1-ethyl-1-hydroxy-2-methyl-propyl) -phenol or after
  • Method E First, according to DE 44 26 245 or US 6,248,737 3- (3-dimethylamino-1-ethyl-1-hydroxy-2-methyl-propyl) -phenol
  • Procedure H (alternative) for all metabolites: Dissolve 1-dimethylamino-3- (3-methoxyphenyl) -2-methylpentan-3-ol in TRIS / HCl buffer pH 7.4. MgCI and optionally the other known cofactors known for CytP450 added and incubated with a mixture of subtypes of cytochrome P450 (CytP450), in particular CytP450 3A4 (N-demethylation) and / or CytP450 2D6 (O-demethylation and hydroxylation) at 37 ° C. The mixture is then separated by HPLC and the metabolites in the fractions identified by NMR and thus isolated.
  • CytP450 cytochrome P450
  • CytP450 3A4 N-demethylation
  • CytP450 2D6 O-demethylation and hydroxylation
  • Example 2 Test System Cystometry on the awake naive rat
  • Threshold pressure (threshold pressure TP, bladder pressure immediately before micturition)
  • ICI intercontraction interval
  • TP threshold pressure
  • ICI Intercontraction Interval
  • the mean value of 3 micturition cycles was determined and represented as a percentage change from the initial value (Table 1).
  • Table 1 Influence of the cystometric parameters by the test substances (change to the initial value [%]); n corresponds to the number of experimental animals; Significance (Student T-Test): * p ⁇ 0.05; ** p ⁇ 0.01; *** p ⁇ 0.001.
  • the examined substances show a positive effect on bladder regulation and are thus suitable for the treatment of urinary incontinence.
  • the (+) - enantiomer (compound 2) is very active (and thus is a particularly preferred compound of this invention) while the (-) enantiomer (compound 21) is not contributed so much to the effect.

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  • General Chemical & Material Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • Urology & Nephrology (AREA)
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  • General Health & Medical Sciences (AREA)
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Abstract

L'invention concerne l'utilisation de composés de 1-phényle-3-diméthylamino-propane pour réaliser un médicament destiné au traitement de l'urgence mictionnelle ou de l'énurésie. La présente invention porte également sur des médicaments et des procédés correspondants pour traiter l'urgence mictionnelle ou l'énurésie.
PCT/EP2003/005490 2002-05-30 2003-05-26 Metabolite de 1-dimethylamino-3-(3-methoxy-phenyle)-2-methyle-pentane-3-ole et son utilisation pour traiter l'enuresie WO2003101440A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP03732465A EP1507521A1 (fr) 2002-05-30 2003-05-26 Metabolite de 1-dimethylamino-3-(3-methoxy-phenyle)-2-methyle-pentane-3-ole et son utilisation pour traiter l'enuresie
AU2003238398A AU2003238398A1 (en) 2002-05-30 2003-05-26 Metabolite of 1-dimethylamino-3-(3-methoxy-phenyl)-2-methyl-pentane-3-ol and the use thereof in the treatment of urinary incontinence
US10/999,219 US20050137145A1 (en) 2002-05-30 2004-11-30 Metabolites of 1-dimethylamino-3-(3-methoxy-phenyl)-2-methyl-pentan-3-ol and their use in the treatment of urinary incontinence

Applications Claiming Priority (2)

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DE10224624A DE10224624A1 (de) 2002-05-30 2002-05-30 Metabolite und Prodrugs von 1-Dimethylamino-3-(3-methoxy-phenyl)-2-methyl-pentan-3-ol
DE10224624.6 2002-05-30

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0013749A1 (fr) * 1979-01-13 1980-08-06 BASF Aktiengesellschaft Hexahydro-1,4-oxazépines, procédé pour leur préparation et compositions pharmaceutiques les contenant
DE4426245A1 (de) * 1994-07-23 1996-02-22 Gruenenthal Gmbh 1-Phenyl-3-dimethylamino-propanverbindungen mit pharmakologischer Wirkung
WO2001024783A2 (fr) * 1999-10-05 2001-04-12 Grünenthal GmbH Utilisation de (+)-tramadol, de o-demethyltramadol ou de (+)-o-demethyltramadol, de o-desmethyle-n-mono-desmethyl-tramadol ou de (+)o-desmethyl-n-mono-desmethyl-tramadol pour traiter l'incontinence urinaire
WO2002043715A2 (fr) * 2000-11-30 2002-06-06 Grünenthal GmbH Utilisation de composes 1-phenyl-3-dimethylamino-propane pour traiter l'incontinence urinaire

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19609847A1 (de) * 1996-03-13 1997-09-18 Gruenenthal Gmbh Dimethyl-(3-aryl-but-3-enyl)-aminverbindungen als pharmazeutische Wirkstoffe

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0013749A1 (fr) * 1979-01-13 1980-08-06 BASF Aktiengesellschaft Hexahydro-1,4-oxazépines, procédé pour leur préparation et compositions pharmaceutiques les contenant
DE4426245A1 (de) * 1994-07-23 1996-02-22 Gruenenthal Gmbh 1-Phenyl-3-dimethylamino-propanverbindungen mit pharmakologischer Wirkung
WO2001024783A2 (fr) * 1999-10-05 2001-04-12 Grünenthal GmbH Utilisation de (+)-tramadol, de o-demethyltramadol ou de (+)-o-demethyltramadol, de o-desmethyle-n-mono-desmethyl-tramadol ou de (+)o-desmethyl-n-mono-desmethyl-tramadol pour traiter l'incontinence urinaire
WO2002043715A2 (fr) * 2000-11-30 2002-06-06 Grünenthal GmbH Utilisation de composes 1-phenyl-3-dimethylamino-propane pour traiter l'incontinence urinaire

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AU2003238398A1 (en) 2003-12-19
EP1507521A1 (fr) 2005-02-23
AR039901A1 (es) 2005-03-09
DE10224624A1 (de) 2003-12-11
PE20040521A1 (es) 2004-08-24

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