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WO1999021839A1 - Composes heterocycliques et leur utilisation - Google Patents

Composes heterocycliques et leur utilisation Download PDF

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Publication number
WO1999021839A1
WO1999021839A1 PCT/JP1998/004807 JP9804807W WO9921839A1 WO 1999021839 A1 WO1999021839 A1 WO 1999021839A1 JP 9804807 W JP9804807 W JP 9804807W WO 9921839 A1 WO9921839 A1 WO 9921839A1
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Prior art keywords
group
methyl
naphthyl
tetrahydro
acceptable salt
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Ceased
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PCT/JP1998/004807
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English (en)
Japanese (ja)
Inventor
Ichiro Koga
Atsushi Okada
Kazuhisa Narita
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Nippon Kayaku Co Ltd
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Nippon Kayaku Co Ltd
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Priority to AU96469/98A priority Critical patent/AU9646998A/en
Publication of WO1999021839A1 publication Critical patent/WO1999021839A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members

Definitions

  • the present invention relates to a novel heterocyclic compound, a medicament, and an agent for treating or preventing urinary frequency or urinary incontinence, and is useful in the field of medicine.
  • Drugs used for the treatment or prophylaxis of pollakiuria or urinary incontinence include anticholinergic (muscling) agents, smooth muscle direct relaxants, antidepressants (for example, tricyclic antidepressants), stimulants for estrogen receptors, estrogens Formulations, autonomic nervous regulators or minor tranquilizers are used.
  • ⁇ represents an unsubstituted or substituted indanyl group, a naphthyl group or a tetrahydronaphthyl group
  • X represents a general formula (2)
  • R 1 represents a hydrogen atom or a lower alkyl group, a cycloalkyl group, or an unsubstituted or substituted phenyl group
  • R 2 and R 3 are the same or different and represent a hydrogen atom or a lower alkyl group.
  • M represents an integer 1 or 2
  • B represents an unsubstituted or substituted heterocyclic ring. Or a pharmacologically acceptable salt thereof.
  • B is an unsubstituted or substituted 5- to 6-membered ring containing 1 to 3 nitrogen atoms, and optionally a heterocyclic compound which may contain one oxygen atom. Is its pharmacologically acceptable salt.
  • R 2 and R 3 are the same or different and represent a hydrogen atom or a lower alkyl group having 1 to 5 carbon atoms; Selected from alkyl groups having 1 to 3 carbon atoms, alkenyl groups having 3 to 5 carbon atoms, halogens, benzyl groups, phenethyl groups, cycloalkyl groups having 3 to 7 carbon atoms, phenyl groups, nitro groups, cyano groups and mercapto groups
  • Optionally substituted imidazolyl group, the same imidazolinyl group, the same imidazolidinyl group, the same triazolyl group, the same pyrrolidinyl group, the same piperidinyl group, the same homopiperidinyl group, the same group Ruhoriniru group, are allowed heterocyclic compound or a pharmacologically according to any one of the
  • heterocyclic compound or a pharmaceutically acceptable salt thereof according to any one of the above 1 to 4, wherein m represents an integer 1 and B represents an unsubstituted or substituted imidazolyl group.
  • X is a group represented by the general formula (2), is a hydrogen atom, R 2 is a lower alkyl group, and R 3 is a hydrogen atom.
  • a physically acceptable salt is a group represented by the general formula (2), is a hydrogen atom, R 2 is a lower alkyl group, and R 3 is a hydrogen atom.
  • X is a group represented by the general formula (3), is a hydrogen atom, and R 2 is a lower alkyl group, or a pharmaceutically acceptable heterocyclic compound according to any one of the above 1 to 5. salt.
  • a ri represents a 5,6,7,8-tetrahydro-1-naphthyl group substituted at the 4-position with a hydroxy group or a lower alkoxy group, or a compound thereof.
  • Pharmacologically acceptable salt
  • heterocyclic compound or a pharmaceutically acceptable salt thereof according to any one of the above 1 to 7, wherein B represents a 2-lower alkyl-1H-imidazole-11yl group.
  • Ar 2 represents an unsubstituted or substituted phenyl group, an indanyl group, a naphthyl group, or a tetrahydronaphthyl group
  • X represents the general formula (2)
  • R 1 represents a hydrogen atom or a lower alkyl group, a cycloalkyl group or an unsubstituted or substituted phenyl group
  • R 2 and R 3 are the same or different and represent a hydrogen atom or a lower alkyl group.
  • M represents an integer 1 or 2
  • B represents an unsubstituted or substituted heterocyclic ring.
  • a therapeutic or prophylactic agent for pollakiuria or urinary incontinence comprising, as an active ingredient, a heterocyclic compound represented by the formula or a pharmacologically acceptable salt thereof.
  • a heterocyclic compound or a drug thereof wherein B is an unsubstituted or lower alkyl-substituted 5- to 6-membered ring containing 1 to 3 nitrogen atoms and optionally showing a heterocycle optionally containing one oxygen atom.
  • B is an unsubstituted or lower alkyl-substituted 5- to 6-membered ring containing 1 to 3 nitrogen atoms and optionally showing a heterocycle optionally containing one oxygen atom.
  • Ar 2 is an alkyl group having 1 to 3 carbon atoms, a halogen, a halogenoalkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a benzyloxy group, a benzyl group, A phenyl group, an indanyl group, a naphthyl group, or a tetrahydronaphthyl group which may have a substituent selected from a cyano group and a nitro group, and R i represents a hydrogen atom or a carbon atom having 1 to 5 carbon atoms; A lower alkyl group, a cycloalkyl group or an unsubstituted or substituted phenyl group; R 2 and R 3 are the same or different and represent a hydrogen atom or a lower alkyl group having 1 to 5 carbon atoms; Alkyl group having 3 to 5 carbon atoms, alkenyl group having 3 to 5 carbon atoms,
  • imidazolyl group imidazolinyl group, imidazolidinyl group, triazolyl group, pyrrolidinyl group, piperidinyl group, homopiperidinyl group
  • a therapeutic or prophylactic agent is optionally having imidazolyl group, imidazolinyl group, imidazolidinyl group, triazolyl group, pyrrolidinyl group, piperidinyl group, homopiperidinyl group
  • Ar 2 represents an unsubstituted or substituted phenyl group, an indanyl group, a naphthyl group or a tetrahydronaphthyl group, m represents an integer 1, and B represents unsubstituted or substituted imidazolyl.
  • a medicament comprising as an active ingredient the heterocyclic compound or the pharmacologically acceptable salt thereof described in 1 to 10 above.
  • the compound of the present invention may be a hydrogen atom or a lower alkyl group having 1 to 5 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, and isoamyl; Cycloalkyl group having 3 to 6 carbon atoms, unsubstituted or alkyl group having 1 to 3 carbon atoms such as methyl, ethyl, n-propyl, i-propyl, halogen atom such as chlorine atom, bromine atom and fluorine atom, trifluoromethyl C1-C3 halogeno lower alkyl groups such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, n-pentyloxy, cyclopropylmethoxy, aryloxy, etc.
  • R 2 and R 3 are the same or different and each represent a hydrogen atom or a lower alkyl group.
  • the lower alkyl group include, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, Examples thereof include an alkyl group having 1 to 5 carbon atoms such as n-pentyl, and an alkyl group having 1 to 3 carbon atoms is preferable.
  • Examples of the substituent of A r, and A r 2 include an alkyl group having 1 to 3 carbon atoms such as methyl, ethyl, n-propyl, i-propyl, a haegen atom such as a chlorine atom, a bromine atom, and a fluorine atom; C 1-3 halogeno lower alkyl groups such as trifluoromethyl, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, n-pentyloxy, cyclopropylmethoxy, aryloxy, etc.
  • a substituent such as an alkoxy group having 1 to 5 carbon atoms, a benzyloxy group, a benzyl group, a cyano group, a nitro group, etc., and having 1 to 7 substituents selected from these groups.
  • Ar is a naphthyl having a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or a benzyloxy group as a substituent at the 4-position, a tetrahydronaphthyl or an indanyl group at the 4-position
  • Ar 2 is a 4-position And a phenyl, naphthyl, tetrahydronaphthyl or indanyl group having a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or a benzyloxy group as a substituent.
  • B and R are unsubstituted or alkyl groups having 1 to 3 carbon atoms such as methyl, ethyl, n-propyl, i-propyl, and alkenyl groups having 3 to 5 carbon atoms such as propenyl and 2-butenyl; Halogen atoms such as iodine atom and bromine atom, aralkyl groups such as benzyl and phenethyl, or substituents such as cycloalkyl group having 3 to 7 carbon atoms, phenyl group, nitro group, cyano group, and mercapto group may be the same or different.
  • Imidazolyl group imidazolinyl group, imidazolidinyl group, triazolyl group, pyrrolidinyl group, piperidinyl group, homopiperidinyl group, morpholinyl group, morpholinyl group, piperazinyl group, or homopiperazinyl group having 3 to 3 groups.
  • B has a substituent, an alkyl group having 1 to 3 carbon atoms is preferable.
  • m is represented by an integer of 1 to 2, and is preferably 1.
  • Examples of pharmacologically acceptable salts of the compound represented by formula (1) or (4) include salts with mineral acids such as hydrochloric acid and sulfuric acid, methanesulfonic acid and p-toluenesulfonic acid. And salts with organic carboxylic acids such as acetic acid, propionic acid, succinic acid, lactic acid, tartaric acid, malic acid, and the like.
  • the compound of the present invention represented by the general formula (4) or a pharmacologically acceptable salt thereof is used as a medicament
  • the compound may be used alone, but it is usually a pharmaceutically acceptable pharmaceutical additive.
  • carriers, excipients, diluents and the like can be combined as required to form powders, granules, tablets, capsules, injections, etc., and used as pharmaceutical compositions. it can.
  • the amount of the compound of the present invention represented by the general formula (4) or a pharmaceutically acceptable salt thereof in the preparation is preferably in the range of 0.01 to 100% by weight.
  • Routes of administration include oral, rectal, nasal, topical (including puccal and sublingual), vaginal, bladder, parenteral (including subcutaneous, intramuscular, intravenous and intradermal) and transdermal (ointment, cream) , A patch or the like).
  • the preferred route will be determined by the condition and age of the patient and the condition to be treated.
  • the dosage depends on the route of administration, the age of the patient and the actual condition to be treated.For example, for oral administration to adults, 0.1 mg to 2000 mg / day, preferably 1 mg to 10 mg / day as the active ingredient Can be administered once or several times a day.
  • the method for producing the compound of the present invention is described below. Steps 1-1 and 112 apply only to the preparation of the intermediate, a compound of general formula (6), while steps 1-3 include general formula (10) [including compounds of general formula (6) ] Applied to the manufacture of
  • Examples of the compound of the general formula (10) which is an intermediate of the compound of the present invention include the following compounds.
  • Ar 2 — CO— C CH 2 ⁇ Ar 2 -CO-CH- CH2-B
  • the unsaturated ketone represented by the general formula (5) can be converted into various heterocyclic compounds (BH) And a Michael addition reaction to synthesize a compound of the general formula (6).
  • the amount of the heterocyclic compound to be used is generally 0.5 to 5 equivalents, preferably 1 to 2 equivalents, relative to the compound of general formula (5).
  • the reaction is preferably performed in a solvent, and the solvent is not particularly limited, but alcohols such as methanol, ethanol, and n-propanol; halogenated solvents such as dichloromethane and chloroform; and esters such as ethyl acetate.
  • ketones such as acetone, ethers such as tetrahydrofuran, dioxane and ether, dimethyl sulfoxide, dimethylformamide, water and the like.
  • alcohols or a mixed solvent of alcohols and esters is used.
  • the reaction temperature is from 0 ° C to around the boiling point of the solvent, preferably from 10 ° C to around the boiling point of the solvent, and the reaction time is usually from 0.5 to 24 hours, preferably from 1 to 5 hours.
  • Purification can be carried out by extraction from the reaction solution, followed by recrystallization or by column chromatography such as silica gel.
  • Examples of the compound of the general formula (5) include the following compounds.
  • heterocyclic compound represented by the formula BH include the following imidazole and triazole compounds.
  • NR 4 R 5 is an alkylamino group such as a methylamino group, a dimethylamino group, an ethylamino group, a acetylamino group, or a pyrrolidino group, a piperidino group, or a morpholino group.
  • R 6 represents methyl or ethyl
  • X- represents a halide ion such as chloride ion, bromide ion, iodide ion or sulfate ion, or an anion represented by R 6 S 0 ⁇ N represents an integer of 1/2 or 1 or more.
  • BH heterocyclic compounds
  • the quaternary salt of the general formula (7) is prepared by preparing the corresponding tertiary amine in an appropriate solvent (for example, alcohols such as methanol, ethanol, n-propanol, halogen-based solvents such as dichloromethane and chloroform, acetic acid).
  • Esters such as ethyl, ethers such as tetrahydrofuran and dioxane, dimethyl sulfoxide and dimethylformamide), and methyl bromide and iodine.
  • Ar 2 , R 2 , R 3 , m, and B are the same as defined above, and Y is a halogen such as chlorine, bromine, or iodine, or methanesulfonyloxy, toluenesulfonyloxy, or an acetoxyl group. And the like.
  • the compound of the general formula (10) is synthesized by reacting the halide or the acyloxy compound represented by the general formula (9) with various heterocyclic compounds (BH).
  • the compound of the general formula (9) has the corresponding general formula (8)
  • Ar 2 , R 2 , R 3 and m are the same as defined above.
  • Y is a halogen such as chlorine, bromine or iodine
  • a halogenating agent such as phosphorus trihalide (for example, phosphorus trichloride).
  • phosphorus trihalide for example, phosphorus trichloride
  • Y is an acyloxy group such as methanesulfonyloxy, toluenesulfonyloxy, acesoxy, etc.
  • the compound of the general formula (8) is converted to an acid anhydride or a sulfonyl halide (for example, methanesulfonyl chloride). It can be obtained by reacting with an agent.
  • the amount of the heterocyclic compound to be used is generally 0.5-5 equivalents, preferably 1-2 equivalents, relative to the compound of general formula (9), and the reaction is preferably carried out in a solvent, and the solvent is particularly limited.
  • Alcohols such as methanol, ethanol and n-propanol; halogenated solvents such as dichloromethane and chloroform; ketones such as acetone; ethers such as tetrahydrofuran and dioxane; dimethyl sulfoxide; It is readily formed by reaction with an alkylating agent such as methyl iodide or dimethyl sulfate, preferably methyl iodide or dimethyl sulfate.
  • the amount of the heterocyclic compound to be used is generally 0.5-5 equivalents, preferably 1-2 equivalents, relative to the compound of general formula (7).
  • the reaction is preferably carried out in a solvent.
  • the solvent is not particularly limited, but alcohols such as methanol, ethanol and n-propanol, halogen solvents such as dichloromethane and chloroform, and esters such as ethyl acetate. And ketones such as acetone, ethers such as tetrahydrofuran and dioxane, dimethyl sulfoxide, dimethylformamide, and water.Preferably, alcohols or a mixed solvent of alcohols and esters is used. I do.
  • the reaction temperature is from 0 ° C.
  • reaction time is usually from 0.5 to 24 hours, preferably from 1 to 5 hours.
  • recrystallization or column chromatography such as silica gel can be used.
  • Examples of the quaternary salt represented by the general formula (7) include the following compounds.
  • Examples thereof include dimethylformamide and water.
  • alcohols or halogen-based solvents such as dichloromethane and chloroform are used, dimethylsulfoxide and dimethylformamide are used.
  • the reaction temperature is usually 0 ° C. to around the boiling point of the solvent, preferably 10 ° C. to around the boiling point of the solvent, and the reaction time is usually 0.5 to 24 hours, preferably 1 to 5 hours.
  • Purification can be performed by a method such as recrystallization or column chromatography using silica gel after extraction from the reaction solution.
  • Examples of the halide or acyloxy compound represented by the general formula (9) include the following compounds.
  • the compound of the general formula (11) is synthesized by subjecting the compound of the general formula (10) to a reduction reaction with a metal hydride such as lithium aluminum hydride, sodium borohydride, or isobutylaluminum hydride.
  • a metal hydride such as lithium aluminum hydride, sodium borohydride, or isobutylaluminum hydride.
  • the amount of the metal hydride to be used is generally 0.25 to 5 equivalents, preferably 0.5 to 2 equivalents, relative to the compound of the general formula (10).
  • the solvent include, but are not limited to, alcohols such as methanol, ethanol, and n-propanol; halogen solvents such as dichloromethane and chloroform; and ethers such as tetrahydrofuran and dioxane.
  • the reaction temperature is from about 78 ° C.
  • reaction time is usually from 0.5 to 24 hours, preferably from 1 to 12 hours.
  • Purification can be carried out by extraction from the reaction solution, followed by recrystallization or column chromatography such as silica gel.
  • Ar 2 -CO-CR3 one (CH 2 ) m -B ⁇ Ar 2 -C R7-CR3-(CH 2 ) m — B
  • R 7 represents a lower alkyl group, a cycloalkyl group or an unsubstituted or substituted phenyl group.
  • a compound represented by the general formula (10) is a compound represented by the formula R-M, for example, a Grignard reagent such as methylmagnesium iodide, butylmagnesium bromide, benzylmagnesium chloride or phenylmagnesium bromide, or methyllithium or ethyllithium.
  • the compound of the general formula (12) is synthesized by reacting the compound with an organolithium reagent such as lithium, phenyllithium or the like.
  • the amount of the Grignard reagent or organolithium reagent to be used is generally 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to compound of general formula (10).
  • the solvent examples include ethers such as tetrahydrofuran and dioxane.
  • the reaction temperature is from ⁇ 78 ° C. to around the boiling point of the solvent, preferably ⁇ 78 ° C. to 30 ° C., and the reaction time is usually 0.5 to 24 hours, preferably 1 to 12 hours. After extraction from the reaction solution, it can be carried out by recrystallization or by a method such as column chromatography using a silica gel.
  • Ar 2 -CRi-CH-(CH 2 ) mB ⁇ Ar2-CRi CR 2- (CH 2 ) mB
  • the compound of the general formula (14) is synthesized by subjecting the compound of the general formula (13) to a dehydration reaction using an appropriate acid.
  • the acid include mineral acids such as hydrochloric acid and sulfuric acid, organic sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid, and organic carboxylic acid salts such as acetic acid, propionic acid, succinic acid, lactic acid, tartaric acid, and malic acid. These acids may be used as a mixture.
  • the amount of the acid to be used is generally 1 equivalent-solvent amount relative to the compound of general formula (13).
  • the solvent examples include, but are not limited to, alcohols such as methanol, ethanol, and n-propanol; halogenated solvents such as dichloromethane dichloromethane; ketones such as acetone; and ethers such as tetrahydrofuran and dioxane. And dimethylsulfoxide, dimethylformamide, water and the like. Preferably, no solvent or alcohols, acetone, dioxane, dimethylsulfoxide, dimethylformamide, water and the like are used.
  • the reaction temperature is usually from 0 ° C. to around the boiling point of the solvent, preferably from 20 ° C.
  • reaction time is usually from 0.25 to 24 hours, preferably from 0.25 to 5 hours. If the product precipitates as crystals, it is only necessary to filter it after cooling.Otherwise, extraction from the reaction solution is followed by recrystallization or column chromatography using silica gel. it can.
  • Ar 3 represents a phenyl having an alkoxy group having 1 to 5 carbon atoms as a substituent, the same naphthyl, the same tetrahydronaphthyl or the same indanyl group
  • Ar 4 represents a phenyl having a hydroxyl group generated by cleavage of an ether bond, It represents the same naphthyl, the same tetrahydronaphthyl, or the same indanyl group.
  • the compound of the general formula (16) is synthesized by treating the compound of the general formula (15) with an appropriate reagent.
  • the reagent include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, Lewis acids such as aluminum chloride and boron tribromide, and halogenoalkylsilanes such as trimethylsilyl iodide.
  • the amount of the reagent to be used is generally 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to the compound of the general formula (15).
  • the amount is usually a solvent amount.
  • the solvent is not particularly limited, but when a Lewis acid or halogenoalkylsilane is used, halogenated solvents such as dichloromethane and chloroform, aromatic hydrocarbons such as benzene and toluene, esters such as ethyl acetate, and acetonitrile are used. Among them, a halogen-based solvent such as dichloromethane or chloroform is preferably used. When using mineral acids, alcohols such as methanol, ethanol, n-propanol, etc. Methyl sulfoxide, dimethylformamide, water and the like.
  • the reaction temperature is usually about 10 ° C. to about the boiling point of the solvent, but preferably ⁇ 10 ° C.
  • reaction time is generally 0.5 to 24 hours, preferably 1 to 5 hours. If the product precipitates as crystals, it can be purified only by cooling and then collecting by filtration. After extraction from, it can be performed by a method such as recrystallization or column chromatography on silica gel. [Evaluation]
  • the drug was administered through the common jugular vein.
  • the effect of the drug was expressed as the prolongation coefficient of rhythmic bladder contraction after administration.
  • the extension coefficient was determined by the following equation.
  • Elongation coefficient maximum value of contraction interval after administration / average value of contraction interval for 10 minutes before administration
  • Control drug A Propiverine hydrochloride
  • Control drug B flavoxalate hydrochloride
  • VITR IDE registered trademark [sodium bis (2-methoxyethoxy) aluminum-65% toluene solution] (4.18 g, 13 mmol) was added with 50 ml of toluene, and 2 — [(2 —Methyl-1H—Imidazol-1-yl) methyl] 1 1- (4-Propoxy-1,5,6,7,8-tetrahydro-1-naphthyl) 1-1—Buyunone (0.92 g, 2 50 ml of a 4 mmo 1) methylene chloride solution was added dropwise. After water was added to the reaction solution, the mixture was extracted with ethyl acetate, dried over magnesium sulfate, and concentrated under reduced pressure.
  • 3-(2-ethyl-1 H-imidazole-1-1)-1-(4-methoxy-5, 6,7,8-Tetrahydro-1-naphthyl-12-methyl-11-propanone (3.70 g, 11 mmo 1) is dissolved in 8 ml of methanol and sodium borohydride (60 Omg, 16 mmo 1) was added little by little, and after stirring at room temperature for 24 hours, water was added to the reaction solution, followed by extraction with ethyl acetate. After drying over magnesium sulfate, the solvent was concentrated under reduced pressure, 10 ml of 1N hydrochloric acid was added to the residue, and the mixture was refluxed for 3 hours. After cooling, the precipitated crystals are collected by filtration.
  • the compound of the present invention is novel and shows the same or higher efficacy as the existing therapeutic agent for pollakiuria and urinary incontinence, and is expected as a medicament, especially as a new therapeutic agent for pollakiuria and incontinence.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne de nouveaux médicaments ou agents préventifs contre la miction fréquente ou l'incontinence urinaire présentant une utilité supérieure par rapport aux médicaments existants. Spécifiquement, l'invention concerne des composés hétérocycliques représentés par la formule (1): Ar1-X-(CH2)m-B, ou ses sels acceptables sur le plan pharmacologique, lesquels sont utiles en tant que médicaments ou agents préventifs contre la miction fréquente ou l'incontinence urinaire, et des médicaments ou des agents préventifs tels que décrits ci-dessus et contenant lesdits composés en tant que principe actif. Dans ladite formule Ar représente phényle, indanyle, naphtyle ou tétrahydronaphtyle facultativement substitué; X représente -C(OH)R1-CR2R3 ou -CR1=CR3- (où R1 représente hydrogène, alkyle inférieur, cycloalkyle ou phényle facultativement substitué; et R2 ainsi que R3 sont identiques ou différents et représentent chacun hydrogène ou alkyle inférieur); m est un nombre entier égal à 1 ou 2; et B représente un hétérocycle facultativement substitué:
PCT/JP1998/004807 1997-10-27 1998-10-23 Composes heterocycliques et leur utilisation Ceased WO1999021839A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU96469/98A AU9646998A (en) 1997-10-27 1998-10-23 Heterocyclic compounds and use thereof

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Application Number Priority Date Filing Date Title
JP30950497 1997-10-27
JP9/309504 1997-10-27

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WO1999021839A1 true WO1999021839A1 (fr) 1999-05-06

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Cited By (1)

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WO2006112565A1 (fr) * 2005-04-21 2006-10-26 Dreampharma Corp. Medicaments permettant de traiter la pollakiurie et l'incontinence urinaire, contenant un propiophenone presentant une activite optique et les sels de celui-ci

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WO1998000141A1 (fr) * 1996-07-01 1998-01-08 Sepracor, Inc. Procedes et compositions de traitement de l'incontinence urinaire par (s)-trihexyphenidyle enrichi en enantiomere
WO1998000140A1 (fr) * 1996-07-01 1998-01-08 Sepracor, Inc. Procedes et compositions de traitement de l'incontinence urinaire a l'aide de (r)-trihexyphenidyle enrichi en enantiomeres
WO1998037070A1 (fr) * 1997-02-21 1998-08-27 Takeda Chemical Industries, Ltd. Composes a anneaux condenses, leur procede de production et leur utilisation

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JPS55162777A (en) * 1979-03-09 1980-12-18 Syntex Inc 11*naphthyllnnpropyl*imidazole derivative* its manufacture and medicinal composition containing same
JPH07508514A (ja) * 1992-06-26 1995-09-21 フアルマシア・エ・アツプジヨン・エツセ・ピー・アー セレトニン性，ドーパミン性およびアドレナリン性の活性を有するｎ（ヘテロ）−アリール−ｎ（ヘテロ）−テトラリン−アルキル−ピペラジン
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