WO1993005019A1 - Derives d'indole servant d'inhibiteur de 5-alpha-reductase - Google Patents

Derives d'indole servant d'inhibiteur de 5-alpha-reductase Download PDF

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Publication number
WO1993005019A1
WO1993005019A1 PCT/JP1992/001152 JP9201152W WO9305019A1 WO 1993005019 A1 WO1993005019 A1 WO 1993005019A1 JP 9201152 W JP9201152 W JP 9201152W WO 9305019 A1 WO9305019 A1 WO 9305019A1
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Prior art keywords
compound
salt
alkyl
cdc1
formula
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Application number
PCT/JP1992/001152
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English (en)
Inventor
Satoshi Okada
Kozo Sawada
Natsuko Kayakiri
Yuki Saitoh
Hirokazu Tanaka
Masashi Hashimoto
Original Assignee
Fujisawa Pharmaceutical Co., Ltd.
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
Priority claimed from US07/757,522 external-priority patent/US5212320A/en
Application filed by Fujisawa Pharmaceutical Co., Ltd. filed Critical Fujisawa Pharmaceutical Co., Ltd.
Priority to EP92919507A priority Critical patent/EP0603278A1/fr
Priority to JP5505114A priority patent/JPH07501790A/ja
Publication of WO1993005019A1 publication Critical patent/WO1993005019A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • 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
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to novel indole derivatives and a pharmaceutically acceptable salt thereof. More particularly, it relates to novel indole derivatives and a pharmaceutically acceptable salt thereof which have pharmacological activities such as inhibitory activity on testosteron 5 ⁇ -reductase and the like, to process for preparation thereof, to a pharmaceutical composition comprising the same and to a use of the same as a medicament.
  • one object of the present invention is to provide novel indole derivatives and a pharmaceutically acceptable salt thereof, which are useful as a testosteron 5 ⁇ -reductase inhibitor.
  • Another object of the present invention is to provide process for preparation of said indole derivatives or a salt thereof.
  • a further object of the present invention is to provide a pharmaceutical composition comprising, as an active ingredient, said indole derivatives or a pharmaceutically acceptable salt thereof.
  • Still further object of the present invention is to provide a use of said indole derivatives or a pharmaceutically acceptable salt thereof as a medicament such as testosteron 5 ⁇ -reductase inhibitor useful for treating or preventing testosteron 5 -reductase mediated diseases such as alopecia, acnes, prostatism, and the like in human being or animals.
  • the indole derivatives of the present invention are novel and can be represented by the formula (I) :
  • R is aryl which may have suitable substituent(s), 2 R is carboxy(lower)alky1 or protected
  • X is -0- or -NH- and n is integer of 1 to 6, with proviso that when n is 1, then X is NH, and when n is 3, then ( c n H 2n ) is trimethylene or methylethylene.
  • the object compound (I) and a salt thereof can be prepared by the following processes.
  • R is carboxy(lower)alkyl
  • W2 are each acid residue.
  • the compound (I) o.f the present invention there may be one or more stereoisomeric pairs due to the presence of one or more asymmetric carbon atom(s) and these isomers or a mixture thereof are included within a scope of the compound (I) of the present invention.
  • the starting compound (II), (III) and (IV) can be prepared by the following methods, the details of which are shown in Preparations mentioned below, or a conventional manner.
  • R X, w and n are each as defined above.
  • R is protected hydroxy
  • Suitable salts of the compounds (I) are conventional non-toxic, pharmaceutically acceptable salt and may include a salt with a base or an acid addition salt ' such as a salt with an inorganic base, for example, an alkali metal salt (e.g. sodium salt, potassium salt, cesium salt, etc.), an alkaline earth metal salt (e.g. calcium salt, magnesium salt, etc.), an ammonium salt; a salt with an organic base, for example, an organic amine salt (e.g.
  • triethylamine salt pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, etc.), etc.
  • an inorganic acid addition salt e.g. hydrochloride, hydrobromide, sulf te, phosphate, etc.
  • an organic carboxylic or sulfonic acid addition salt e.g. formate, acetate, trifluoroacetate, maleate, tartrate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, etc.
  • a salt with a basic or acidic amino acid e.g. arginine, aspartic acid, glutamic acid> etc.
  • the preferable example thereof is an acid addition salt.
  • lower is intended to mean 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, unless otherwise indicated.
  • Suitable “lower alkyl” and “lower alkyl moiety” in the terms “carboxy(lower)alkyl” and “protected carboxy(lower)alkyl” may include straight or branched one, having 1 to 6 carbon atom(s), such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, and the like, preferably one having 1 to 4 carbon atoms.
  • halogen means fluoro, chloro, bromo and iodo.
  • Suitable “acid residue” may include halogen (e.g. fluoro, chloro, bromo, iodo), acyloxy (e.g. acetoxy, tosyloxy, mesyloxy, etc.) and the like.
  • Suitable "aryl which may have suitable substituent(s)” may include a conventional group such as aryl (e.g. phenyl, naphthyl, etc.), substituted aryl, for example, lower alkylaryl, for example, lower alkylphenyl
  • protected carboxy(lower)alkyl may include a conventionally protected carboxy such as an esterified carboxy group.
  • ester moiety of an "esterified carboxy” may be the ones such as lower alkyl ester (e.g. methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, tert-butyl ester, pentyl ester, hexyl ester, 1-cyclopropylethyl ester, etc. ) which may have at least one suitable substituent(s) , for example, lower alkanoyloxy(lower)alkyl ester (e.g.
  • acetoxymethyl ester propionyloxymethyl ester, butyryloxymethyl ester, valeryloxymethyl ester, pivaloyloxymethyl ester, hexanoyloxymethyl ester, l(or 2)- acetoxyethyl ester, l(or 2 or 3)-acetoxypropyl ester, 1(or 2 or 3 or 4)-acetoxybutyl ester, l(or 2)-propionyl- oxyethyl ester, l(or 2 or 3)-propionyloxypropyl ester, l(or 2)-butyryloxyethyl ester, l(or 2)-isobutyryloxyethyl ester, l(or 2)-pivaloyloxyethyl ester, l(or 2)-hexanoyloxyethyl ester, isobutyryloxymethyl ester, 2-eth ⁇ lbutyryloxymethyl ester,
  • lower alkanesulfonyl(lower)alkyl ester e.g. 2-mesylethyl ester, etc.
  • mono(or di or tri)-halo(lower)alkyl ester e.g. 2-iodoethyl ester, 2,2,2-trichloroethyl ester, etc.
  • lower alkoxycarbonyloxy(lower)alkyl ester e.g.
  • benzyl ester 4-me hoxybenzyl ester, 4-nitrobenzyl ester, phenethyl ester, trityl ester, benzhydryl ester, bis(methoxyphenyl)methyl ester, 3,4-dimethoxybenzyl ester, 4-hydroxy-3,5-di-tert-butylbenzyl ester, etc. ) ; aryl ester which may have at least one suitable substituent(s) (e.g. phenyl ester, 4-chlorophenyl ester, tolyl ester, tert-butylphenyl ester, xylyl ester, mesityl ester, cumenyl ester, etc. ) ; phthalidyl ester; and the like.
  • suitable substituent(s) e.g. phenyl ester, 4-chlorophenyl ester, tolyl ester, tert-butylphenyl ester, xy
  • the preferred compound can be represented by the formula (I 1 ) shown below.
  • R is aryi which may have suitable substituent(s) [more preferably phenyl which may have suitable substituent(s) ; most preferably lower alkylphenyl]
  • 2 R is carboxy(lower)alkyl, or protected carboxy(lower)- alkyl [more preferably pharmaceutically acceptable esterified carboxy(lower)alkyl; most preferably lower alkoxycarbonyl(lower)alkyl3,
  • X is -O- or -NH-, and n is integer of 1 to 6, with proviso that when n is 1, then X is NH.
  • the preferred compound of the present invention can be represented by the following formula :
  • R 1, R2, X and n are each as defined above.
  • the compound of the following formulae (A) and (B) is also novel, which can be prepared by similar methods as mentioned above or a conventional manner and is of use as a testosteron 5 ⁇ reductase inhibitor.
  • the object compound (I) or a salt thereof can be prepared by reacting the compound (II) or a salt thereof with the compound (III) or a salt thereof.
  • This reaction is usually carried out in a solvent such as alcohol [e.g. methanol, ethanol, etc.], dichloromethane, benzene, N,N-dimethylformamide, tetrahydrofuran, diethyl ether or any other solvent which does not adversely affect the reaction.
  • the reaction may be carried out in the presence of an inorganic or an organic base such as an alkali metal hydroxide [e.g. sodium hydroxide, potassium hydroxide, etc. ], an alkali metal carbonate [e.g.
  • alkali metal bicarbonate e.g. sodium bicarbonate, potassium bicarbonate, etc.
  • alkali metal hydride e.g. sodium hydride, potassium hydride, etc.
  • tri(lower)alkylamine e.g. trimethylamine, triethylamine, diisopropylethylamine, etc.
  • pyridine or its derivative e.g. picoline, lutidine, 4-dimethylaminopyridine, etc.]
  • the base to be used is liquid, it can also be used as a solvent.
  • the reaction temperature is not critical, and the reaction can be carried out under cooling, at room temperature or under warming or heating.
  • the object compound (lb) or a salt thereof can be prepared by subjecting the compound (la) or a salt thereof to elimination reaction of the carboxy protective group.
  • Suitable base may include, for example, an inorganic base such as alkali metal hydroxide (e.g. sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxide (e.g. magnesium hydroxide, calcium hydroxide, etc.), alkali metal carbonate (e.g. sodium carbonate, potassium carbonate, etc.), alkaline earth metal carbonate (e.g. magnesium carbonate, calcium carbonate, etc.), alkali metal bicarbonate (e.g. sodium bicarbonate, potassium bicarbonate, etc.), alkali metal acetate (e.g. sodium acetate, potassium acetate, etc.), alkaline earth metal phosphate (e.g.
  • an inorganic base such as alkali metal hydroxide (e.g. sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxide (e.g. magnesium hydroxide, calcium hydroxide, etc.), alkali metal carbonate (e.g. sodium carbonate, potassium carbonate,
  • alkali metal hydrogen phosphate e.g. disodium hydrogen phosphate, dipotassium hydrogen phosphate, etc.
  • organic base such as trialkylamine (e.g. trimethylamine, triethylamine, etc.), picoline, N-methylpyrrolidine, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-one., 1,4-diazabicyclo[2.2.2]octane, l,5-diazabicyclo[5.4.0]undecene-5 or the like.
  • the hydrolysis using-a base is often carried out in water or a hydrophilic organic solvent or a mixed solvent thereof.
  • Suitable acid may include an organic acid (e.g. formic acid, acetic acid, propionic acid, etc.) and an inorganic acid (e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, etc.).
  • organic acid e.g. formic acid, acetic acid, propionic acid, etc.
  • inorganic acid e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, etc.
  • the present hydrolysis is usually carried out in an organic solvent, water or a mixed solvent thereof.
  • the reaction temperature is not critical, and it may suitable be selected in accordance with the kind of the carboxy protective group and the elimination method.
  • the elimination using Lewis acid is preferable to eliminate substituted or unsubstituted ar(lower)alkyl ester and carried out by reacting the compound (Ig) or a salt thereof with Lewis acid such as boron trihalide (e.g. boron trichloride, boron trifluoride, etc.), titanium tetrahalide (e.g. titanium tetrachloride, titanium tetrabromide, etc.), tin tetrahalide (e.g. tin tetrachloride, tin tetrabromide, etc.), aluminum halide (e.g. aluminum chloride, aluminum bromide, etc. ) , trihaloacetic acid (e.g.
  • boron trihalide e.g. boron trichloride, boron trifluoride, etc.
  • titanium tetrahalide e.g. titanium tetrachloride, titanium tetrabromide, etc
  • This elimination reaction is preferably carried out in the presence of cation trapping agents (e.g. anisole, phenol, etc.) and is usually carried out in a solvent such as nitroalkane (e.g. nitromethane, nitroethane, etc.) , alkylene halide (e.g. methylene chloride, ethylene chloride, etc. ) , diethyl ether, carbon disulfide or any other solvent which does not adversely affect the reaction. These solvents may be used as a mixture thereof.
  • the reduction elimination can be applied preferably for elimination of the protective group such as halo(lower)alkyl (e.g. 2-iodoethyl, 2,2,2-trichloroethyl, etc.) ester, ar(lower)alkyl (e.g. benzyl, etc.) ester or the like.
  • the protective group such as halo(lower)alkyl (e.g. 2-iodoethyl, 2,2,2-trichloroethyl, etc.) ester, ar(lower)alkyl (e.g. benzyl, etc.) ester or the like.
  • the reduction method applicable for the elimination reaction may include, for example, reduction by using a combination of a metal (e.g. zinc, zinc amalgam, etc.) or a salt of chromium compound (e.g. chromous chloride, chromous acetate, etc.) and an organic or an inorganic acid (e.g. acetic acid, propionic acid, hydrochloric acid, etc. ) ; and conventional catalytic reduction is the pressure of a conventional metallic catalyst (e.g. palladium carbon, Raney nickel, etc.).
  • a metal e.g. zinc, zinc amalgam, etc.
  • a salt of chromium compound e.g. chromous chloride, chromous acetate, etc.
  • an organic or an inorganic acid e.g. acetic acid, propionic acid, hydrochloric acid, etc.
  • conventional catalytic reduction is the pressure of a conventional metallic catalyst (e.g. palladium carbon, Raney nickel, etc.).
  • the object compound (I) or a salt thereof can be prepared by reacting the compound (IV) or a salt thereof with the compound (V) or a salt thereof.
  • This reaction can be carried out in substantially the same manner as Process 1, and therefore the reaction mode and reaction conditions [e.g. solvents, reaction temperature, etc.] of this reaction are to be referred to those as explained in Process 1.
  • reaction mode and reaction conditions e.g. solvents, reaction temperature, etc.
  • the object compound (I) of the present invention can be isolated and purified in a conventional manner, for example, extraction, precipitation, fractional crystallization, recrystallization, chromatography, and the like.
  • the object compound (I) thus obtained can be converted . o its salt by a conventional method.
  • the object compound (I) of the present invention is useful as a testosteron 5 ⁇ -reductase inhibitor and effective to testosteron 5 ⁇ -reductase mediated diseases such as prostatism, prostatic hypertrophy, prostatic cancer, alopecia, hirsutism (e.g. female hirsutism, etc.), androgenic alopecia (or male-pattern baldness), acne (e.g. acne vulgaris, pimple, etc.), other hyperandrogenism, and the like.
  • testosteron 5 ⁇ -reductase inhibitor and effective to testosteron 5 ⁇ -reductase mediated diseases such as prostatism, prostatic hypertrophy, prostatic cancer, alopecia, hirsutism (e.g. female hirsutism, etc.), androgenic alopecia (or male-pattern baldness), acne (e.g. acne vulgaris, pimple, etc.), other hyperandrogenism, and the like
  • Test Compound :
  • the reaction solution contains 1 mM dithiothreitol
  • testosterone/testosterone 2.2 x 10-9 M
  • suspension prepared above 0.8 mg of protein
  • Test Compound was added in 10 ⁇ l of 10% ethanol whereas control tubes received the same volume of 10% ethanol.
  • the reaction was started with the addition of the enzyme suspension. After incubation at
  • the object compound (I) of the present invention [and also compounds (A) and (B)] are used in the form of conventional pharmaceutical preparation which contains said compound as an active ingredient, in admixture with pharmaceutically acceptable carriers such as an organic or inorganic solid or liquid excipient which is suitable for oral, parenteral and external administration.
  • pharmaceutical preparation may be in solid form such as tablet, granule, powder, capsule, or liquid form such as solution, suspension, syrup, emulsion, lemonade, lotion and the like.
  • auxiliary substances stabilizing agents, wetting agents and other commonly used additives such as lactose, citric acid, tartaric acid, stearic acid, magnesium stearate, terra alba, sucrose, corn starch, talc, gelatin, agar, pectin, peanut oil, olive oil, cacao butter, ethylene glycol, and the like.
  • dosage of the compound (I) may vary from and also depend upon the age, conditions of the patient, a kind of disease or conditions, a kind of the compound (I) to be applied, etc. In general amounts between 0.01 mg and about 500 mg or even more per day may be administered to a patient.
  • An average single dose of about 0.05 mg, 0.1 mg, 0.25 mg, 0.5 mg, 1 mg, 20 mg, 50 mg, 100 mg of the object compound (I) of the present invention may be used in treating diseases.
  • Propionyl chloride 13.0 ml was added to a suspension of aluminum chloride (20.0 g) in dichloromethane (200 ml) at 0°C. After the mixture was stirred at 0°C for 1 hour, isobutylbenzene (23.6 ml) was added to the mixture. The mixture was stirred at 0°C for 2 hours and poured into ice water. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residual oil was distilled under reduced pressure to give 4'-isobutylpropiophenone as a colorless oil (24.4 g).
  • Example 1 A mixture of ethyl 4-[3-(4-h ⁇ droxybenzoyl)indol-l- yl]butyrate (176 mg), l-(l-bromohexyl)-4-isobutylbenzene (223 mg) and potassium carbonate (207 mg) in- N,N-dimethylformamide (4 ml) was stirred at room temperature for 6 hours. The reaction mixture was filtered and the filtrate was poured into a mixture of ethyl acetate and 0.5N hydrochloric acid. The organic phase was separated, washed with water and brine, dried over magnesium sulfate and evaporated.
  • Example 7 To a solution of ethyl 4-[3-[3-l-(4-isobutylphenyl)- hexylamino]benzoyl]indol-l- ⁇ l]butyrate (150 mg) in ethanol (2 ml) and 1,4-dioxane (2 ml) was added IN aqueous solution of sodium hydroxide (1 ml) . The mixture was stirred at room temperature for 3 hours, and then poured into a mixture of ethyl acetate and 0.5N hydrochloric acid.
  • Example 9 To a mixture of ethyl 4-[3-(4-hydroxybenzoyl)indol- l-yl]butyrate (275 mg) , (R)-l-(4-isobutylphenyl)pentanol (179 mg) and triphenylphosphine (213 mg) in a mixture of tetrahydrofuran and toluene (1:4, 10 ml) was added diethyl azodicarboxylate (0.13 ml) at -25°C. After stirring for 1 hour, the reaction mixture was concentrated in vacuo.
  • Example 13 To a stirred solution of ethyl 4-[3-(4-hydroxy- benzoyl)indol-l-yl]butyrate (131 mg) in N,N-dimethylformamide (1.5 ml) was added (S)-l-chloro- 1-phenylbutane (153 mg) and powdered potassium carbonate (254 mg) , and the mixture was heated at 60°C for 4 hours. The reaction mixture was diluted with ethyl acetate and filtered through celite.
  • Example 15 The following compounds were obtained according to a similar manner to that of Example 3.

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  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)

Abstract

L'invention se rapporte à des dérivés d'indole représentés par la formule suivante (I), ou à un sel de ces dérivés, qui sont utiles comme inhibiteur de la testostérone 5α-réductase.
PCT/JP1992/001152 1991-09-11 1992-09-09 Derives d'indole servant d'inhibiteur de 5-alpha-reductase WO1993005019A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP92919507A EP0603278A1 (fr) 1991-09-11 1992-09-09 Derives d'indole servant d'inhibiteur de 5-alpha-reductase
JP5505114A JPH07501790A (ja) 1991-09-11 1992-09-09 ５−アルファレダクターゼ阻害剤としてのインドール誘導体

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US07/757,522 US5212320A (en) 1990-05-21 1991-09-11 Indole derivatives and their use for testosterone 5-alpha-reductase-mediated diseases
US07/757,522 1991-09-11
US79259591A 1991-11-15 1991-11-15
US07/792,595 1991-11-15

Publications (1)

Publication Number Publication Date
WO1993005019A1 true WO1993005019A1 (fr) 1993-03-18

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EP (1) EP0603278A1 (fr)
JP (1) JPH07501790A (fr)
CA (1) CA2118697A1 (fr)
WO (1) WO1993005019A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994018168A1 (fr) * 1993-02-10 1994-08-18 Fujisawa Pharmaceutical Co., Ltd. Derives d'indole utilises comme inhibiteurs de 5-alpha-reductase
WO1994026710A1 (fr) * 1993-05-17 1994-11-24 Fujisawa Pharmaceutical Co., Ltd. DERIVES D'INDOLE UTILES COMME INHIBITEURS DE LA TESTOSTERONE 5α-REDUCTASE
WO1995026955A1 (fr) * 1994-03-30 1995-10-12 Zeria Pharmaceutical Co., Ltd. Derive d'indole et medicament le contenant
US5543417A (en) * 1994-10-21 1996-08-06 Merck & Co., Inc. Combination method of treating acne using 4-AZA-5α-cholestan-ones and 4-AZA-5α-androstan-ones as selective 5α-reductase inhibitors with anti-bacterial, keratolytic, or anti-inflammatory agents
KR100368297B1 (ko) * 2000-05-31 2003-01-24 이승기 양성 전립선 비대증 치료용 메나퀴논 7

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1492929A (fr) * 1966-05-11 1967-08-25 Roussel Uclaf Nouveaux 1-(omega-carboxyalcoyl) indoles substitués et procédé de préparation
GB1260868A (en) * 1968-01-11 1972-01-19 Roussel Uclaf 0,2,3,6-tetrasubstituted indoles
US3843683A (en) * 1968-02-20 1974-10-22 Sterling Drug Inc Alpha-(3-(4-chlorobenzoyl)-2-methyl-6-methoxy-1-ndole)-acetic acid
EP0149419A1 (fr) * 1983-09-28 1985-07-24 Nippon Zoki Pharmaceutical Co. Ltd. Dérivés d'acyle-indoles et compositions pharmaceutiques les contenant
EP0458207A2 (fr) * 1990-05-21 1991-11-27 Fujisawa Pharmaceutical Co., Ltd. Dérivés d'indole

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1492929A (fr) * 1966-05-11 1967-08-25 Roussel Uclaf Nouveaux 1-(omega-carboxyalcoyl) indoles substitués et procédé de préparation
GB1260868A (en) * 1968-01-11 1972-01-19 Roussel Uclaf 0,2,3,6-tetrasubstituted indoles
US3843683A (en) * 1968-02-20 1974-10-22 Sterling Drug Inc Alpha-(3-(4-chlorobenzoyl)-2-methyl-6-methoxy-1-ndole)-acetic acid
EP0149419A1 (fr) * 1983-09-28 1985-07-24 Nippon Zoki Pharmaceutical Co. Ltd. Dérivés d'acyle-indoles et compositions pharmaceutiques les contenant
EP0458207A2 (fr) * 1990-05-21 1991-11-27 Fujisawa Pharmaceutical Co., Ltd. Dérivés d'indole

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994018168A1 (fr) * 1993-02-10 1994-08-18 Fujisawa Pharmaceutical Co., Ltd. Derives d'indole utilises comme inhibiteurs de 5-alpha-reductase
WO1994026710A1 (fr) * 1993-05-17 1994-11-24 Fujisawa Pharmaceutical Co., Ltd. DERIVES D'INDOLE UTILES COMME INHIBITEURS DE LA TESTOSTERONE 5α-REDUCTASE
WO1995026955A1 (fr) * 1994-03-30 1995-10-12 Zeria Pharmaceutical Co., Ltd. Derive d'indole et medicament le contenant
US5543417A (en) * 1994-10-21 1996-08-06 Merck & Co., Inc. Combination method of treating acne using 4-AZA-5α-cholestan-ones and 4-AZA-5α-androstan-ones as selective 5α-reductase inhibitors with anti-bacterial, keratolytic, or anti-inflammatory agents
KR100368297B1 (ko) * 2000-05-31 2003-01-24 이승기 양성 전립선 비대증 치료용 메나퀴논 7

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CA2118697A1 (fr) 1993-03-18
EP0603278A1 (fr) 1994-06-29
JPH07501790A (ja) 1995-02-23

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