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WO2009031706A1 - Composé de coumarine et son utilisation - Google Patents

Composé de coumarine et son utilisation Download PDF

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Publication number
WO2009031706A1
WO2009031706A1 PCT/JP2008/066484 JP2008066484W WO2009031706A1 WO 2009031706 A1 WO2009031706 A1 WO 2009031706A1 JP 2008066484 W JP2008066484 W JP 2008066484W WO 2009031706 A1 WO2009031706 A1 WO 2009031706A1
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WIPO (PCT)
Prior art keywords
coumarin compound
group
type
compound
formula
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2008/066484
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English (en)
Japanese (ja)
Inventor
Hideki Kubo
Hirohisa Nagahori
Yoshitaka Tomigahara
Junya Takahashi
Koichiro Harada
Akio Tanaka
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sumitomo Chemical Co Ltd
Original Assignee
Sumitomo Chemical Co Ltd
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Filing date
Publication date
Application filed by Sumitomo Chemical Co Ltd filed Critical Sumitomo Chemical Co Ltd
Publication of WO2009031706A1 publication Critical patent/WO2009031706A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
    • 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
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P17/08—Antiseborrheics
    • 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
    • A61P17/10—Anti-acne agents
    • 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
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/26—Androgens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/28—Antiandrogens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a coumarin compound and its use.
  • Male hormone-dependent diseases such as prostate cancer, benign prostatic hypertrophy, acne, seborrhea, hirsutism, androgenetic alopecia, sexual prematurity, adrenal hypertrophy and polycystic ovary syndrome, its onset and progression Promoted by androgenic activity.
  • Type 3 17; 3-hydroxysteroid dehydrogenase is an enzyme that catalyzes the conversion of androstenedione, a low-activity male hormone, to testosterone, a high-activity male hormone.
  • 3-hydroxycysteide dehydrogenase gene is higher than that in normal tissues (eg, The Pros tate, 53, 154-159, (2002)). Disclosure of the invention
  • An object of the present invention is to provide a compound that can inhibit type 3 17 / 3-hydroxysteroide dehydrogenase, and thus is useful in the treatment or prevention of male hormone-dependent diseases.
  • the present invention relates to compounds represented by the following formulas (I) to ( ⁇ ⁇ ) having the ability to inhibit type 3 17-hydroxysteride dehydrogenase (hereinafter collectively referred to as the present compound). Sometimes).
  • the present invention provides:
  • Type 3 17 ⁇ characterized in that it contains a coumarin compound represented by
  • Xj 1 ′ represents a hydrogen atom, a methyl group or a trifluoromethyl group
  • k ′ represents 0 or 1
  • 1 ⁇ ' represents a hydrogen atom or a C1-C2 alkyl group.
  • a type 3 17 ⁇ -hydroxysteroid dehydrogenase inhibitor composition comprising a coumarin compound according to item 2 and an inert carrier;
  • a type 3 17 3-hydroxy steroid dehydrogenase inhibitor composition containing the compound according to 3 to 7 above and an inert carrier;
  • a method for treating or preventing male hormone-dependent diseases comprising a therapeutically effective amount of a type 3 17 ⁇ -hydroxysteride dehydrogenase inhibitor composition according to item 1 as an active ingredient Administering a coumarin compound to a patient in need of the treatment or prevention; and 1 5.
  • Androgen dependent diseases include prostate cancer, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, hirsutism, acne, seborrhea, androgenetic alopecia, sexual prematurity, adrenal hypertrophy or polycystic
  • the method according to the preceding paragraph 14 which is ovarian syndrome;
  • examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • examples of the CI-C4 alkyl group include a methyl group, an ethyl group, an isopropyl group, a t-butyl group, and the like.
  • examples of the C ⁇ C4 alkylcarbonyl group include a acetyl group and a propionyl group.
  • Etc. In this compound, when it has a pyridine ring, its N-talide is included.
  • the compounds also represent their pharmacologically acceptable salts.
  • the pharmacologically acceptable salt represents a salt of the present compound with an inorganic acid, a salt with an organic acid, a salt with an inorganic base or a salt with an organic base.
  • salts with inorganic acids include hydrochlorides and hydrobromides
  • examples of salts with organic acids include acetates and benzoates
  • salts with inorganic bases examples thereof include potassium salts and sodium salts.
  • examples of salts with organic bases include pyridine salts and morpholine salts.
  • the formula ( ⁇ ⁇ ) (where ⁇ ⁇ !, ⁇ ⁇ ! And! Represents meaning.
  • the compound represented by the formula ( ⁇ ⁇ ′) (wherein V represents a chlorine atom or a bromine atom,! And J represent the same meaning as described above.) It can be produced by reacting with a compound represented by the formula (II A ′ ′) (wherein i represents the same meaning as described above).
  • the reaction temperature is usually from room temperature to the solvent reflux temperature, and the reaction time is usually from instantaneous to about 24 hours.
  • the reaction is usually carried out in the presence of a base.
  • the base used include organic bases such as pyridine, triethylamine, N, N-dimethylaniline, triptylamin, N-methylmorpholine, and sodium hydrogenated hydrogen.
  • inorganic bases such as sodium hydroxide, potassium hydroxide and potassium carbonate.
  • Solvents usable in the reaction include aliphatic hydrocarbons such as hexane and petroleum ether, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as chloroform, dichloroethane, and jetyl.
  • Ethers such as ether, dioxane and tetrahydrofuran; Ketones such as acetone and methyl ethyl ketone; Esters such as ethyl acetate and ethyl acetate; Alcohols such as methanol, ethanol and isopropanol; Acetonitrile and Isobutyl nitrile Examples thereof include nitriles, formamides, amides such as N, N-dimethylformamide, sulfur compounds such as dimethylsulfoxide, and the like, or mixtures thereof.
  • reaction solution after completion of the reaction is subjected to usual post-treatment such as organic solvent extraction, washing with water, and decompressing and concentrating the organic layer, and if necessary, purification by chromatography, recrystallization, etc. ( ⁇ ⁇ ) can be obtained.
  • the compound represented by the formula (II B ) (wherein! And! Have the same meaning as above) is, for example, resorcinol ( ⁇ ⁇ ') and formula ( ⁇ ⁇ '' (Wherein ⁇ ⁇ ! IX i! Represents the same meaning as described above, and R B represents a C1-C4 alkyl group.)
  • resorcinol ⁇ ⁇ '
  • formula ( ⁇ ⁇ '' (Wherein ⁇ ⁇ ! IX i! Represents the same meaning as described above, and R B represents a C1-C4 alkyl group.)
  • R B represents a C1-C4 alkyl group.
  • the reaction temperature range is usually 0 ° C. to 120 ° C. with the solvent reflux temperature as the upper limit, and the reaction time range is usually instantaneous to about 50 hours.
  • the reaction is usually performed in an acidic solvent.
  • the acidic solvent include concentrated sulfuric acid, 70% sulfuric acid, trifluoroacetic acid, methanesulfonic acid, oxysulpholine, polyphosphoric acid and the like.
  • the amounts of reagents to be subjected to the reaction, resorcinol (II B ') per 1 mol of compound (II B,') is usually 0.8 to 2 mol, and an acidic solvent, resorcinol (II B ' ) Is usually 5 to 100 times the weight.
  • formula (II C ) (wherein X !, ⁇ and k represent the same meaning as described above, and R c represents a C1-C4 alkyl group).
  • the compound can be produced, for example, by acylating a compound represented by the formula (II C ′) (wherein Xi i,! And k have the same meaning as described above) with an acylating agent. Can do.
  • the reaction temperature is usually from room temperature to the solvent reflux temperature, and the reaction time is usually from instantaneous to about 24 hours.
  • the reaction is usually carried out in the presence of a base.
  • the base used include organic bases such as pyridine, triethylamine, N, N-dimethylaniline, triptylamin, N-methylmorpholine, and imidazole, sodium hydride, 7K
  • examples include inorganic bases such as sodium oxide, potassium hydroxide, and potassium carbonate.
  • the amount of the reagent used for the reaction is usually 1 to 2 moles for the acylating agent and 1 to 7 moles for the base, based on 1 mole of the compound (II C ).
  • a solvent is not necessarily required, but it is usually performed in the presence of a solvent.
  • the solvents mentioned in the production method (1) can be used for the reaction.
  • the acylating agent include acid chlorides such as acetyl chloride and propionyl chloride, and acid anhydrides such as acetic anhydride.
  • the compound represented by the formula (II D ) (wherein !! ⁇ x and k represent the same meaning as described above) is, for example, the formula (II D ′) (wherein t, t and k represent the same meaning as described above, and R D represents a C1-C4 alkyl carbonyl group, which can be produced by hydrolyzing the compound.
  • the reaction temperature is usually from room temperature to the solvent reflux temperature, and the reaction time is usually from instantaneous to about 24 hours.
  • the reaction is usually carried out in the presence of a base, and examples of the base used include inorganic bases such as sodium hydroxide, potassium hydroxide and carbonated lithium.
  • the amount of base used in the reaction is the compound (II D '
  • the base is usually 1-7 moles.
  • the reaction is usually carried out in the presence of a solvent, and usable solvents include ethers such as jetyl ether, dioxane and tetrahydrofuran, ketones such as acetone and methyl ethyl ketone, Alcohols such as methanol, ethanol, isopropanol, nitriles such as acetonitrile, isobutyl nitrile, amides such as formamide, N, N-dimethylformamide, sulfur compounds such as dimethyl sulfoxide, water or a mixture thereof can give.
  • compound UI D can be obtained in the same manner as in production method (1).
  • the compounds (A) represented by compound numbers (1) to (1 1) are represented in Table 1.
  • This compound has the ability to inhibit the activity of type 3 17-hydroxysteride dehydrogenase. This ability is important to prevent the development and progression of male hormone-dependent diseases by inhibiting the production of the highly active androgen testosterone, leading to decreased androgenic activity in tissues. Therefore, the present compound inhibits the activity of male hormone-dependent diseases by inhibiting type 3 17 i3-hydroxysteride dehydrogenase activity and suppressing the enhancement of male hormone activity in tissues. It can be used as an active ingredient in compositions (pharmaceuticals, cosmetics, food additives, etc.).
  • the compound is a method of inhibiting type 3 17; 8-hydroxysteroide mouthgenase, wherein a therapeutically effective amount of at least one compound requires such inhibition It can utilize for the method including the process of administering to a patient.
  • the compound is a method of treating or preventing a male hormone dependent disease, comprising the step of administering a therapeutically effective amount of at least one compound to a patient in need of the treatment or prevention. It can be used for the method of inclusion. This compound is useful for the prevention or treatment of male hormone-dependent diseases whose onset or progression is promoted by the activity of male hormones.
  • Male hormone-dependent diseases to which this compound can be applied include, for example, prostate cancer and other androgen-dependent neoplasms, benign prostatic hypertrophy, prostatic intraepithelial neoplasia, androgenetic alopecia (ie, male patients) Pattern baldness in both female and female patients), hirsutism, polycystic ovary syndrome, premature sexual maturity, adrenal hypertrophy, leakage and acne.
  • a therapeutically effective amount of at least one compound is about 0.00 1 to 1 kg / kg body weight per day. 50 Omg of this compound.
  • a more preferred dosage is about 0.01 to 25 mg of the present compound, or a pharmaceutically acceptable salt of the present compound or a solvate of the present compound, per kg body weight per day.
  • the compound is usually administered in the form of a composition comprising at least one compound, or a pharmacologically acceptable salt of the compound or a solvate of the compound, and at least one inert carrier. .
  • the compounds contained in these compositions are usually from 0.01% to 99.99% by weight, and the inert carrier is usually from 99.99% to 0.01% by weight. .
  • the inert carrier is a pharmaceutically acceptable carrier or excipient.
  • the composition of the present invention may further contain pharmaceutical additives, cosmetic additives, food additives and the like. '' Pharmaceutically acceptable carriers, excipients, pharmaceutical additives, food additives, cosmetic additives, etc. used to prepare the above-mentioned composition containing the present compound are used for specific applications of the composition.
  • the form of the composition can be, for example, various solids, liquids, etc., depending on the specific application.
  • Solid form preparations include powders, tablets, dispersible granules, capsules, cachets and suppositories.
  • the powder and tablets can be comprised of from about 5 to about 95 percent active ingredient.
  • the solid carrier include magnesium carbonate, magnesium stearate, talc, sugar or lactose. Tablets, powders, cachets and capsules can be used as solid dosage forms suitable for oral administration. Examples of pharmaceutically acceptable carriers and methods of manufacture for various compositions are described in A.
  • Liquid form preparations include solutions, suspensions and emulsions.
  • non Water or water-propylene glycol solution for oral injection can be mentioned.
  • Sweeteners and opacifiers may be added to oral solutions, suspensions and emulsions.
  • liquid form preparations may include solutions for intranasal administration. It can also be an aerosol formulation suitable for inhalation, in which case it can include solutions and solids in powder form.
  • Such solids in solution or powder form may be formulated in combination with a pharmaceutically acceptable carrier such as an inert compressed gas (eg, nitrogen).
  • transdermal composition can be in the form of a cream, a lotion, an aerosol and / or an emulsion, and for this purpose, as usual in the art, in a matrix type transdermal patch or reservoir type It may be contained in a transdermal patch.
  • the compound may also be delivered subcutaneously. More preferably, the compound may be administered orally.
  • the composition can also be in unit dosage form. In such form, the composition is subdivided into suitably sized unit doses containing appropriate quantities of the active component, eg, an effective amount to achieve the desired purpose.
  • the amount of active compound in a unit dose of the composition is adjusted to be about 1 mg to about 100 mg, preferably about 1 mg to about 50 mg, more preferably about 1 mg to about 25 mg, according to its particular application. Also good.
  • the actual dosage used may vary depending on the weight of the patient and the severity of the disease being treated. If necessary for convenience, the total daily dosage may be divided into several doses.
  • the amount and frequency of administration of this compound and Z or a pharmacologically acceptable salt of this compound will depend on factors such as the patient's age, condition and physique, and the severity of the disease being treated. It is adjusted according to the judgment.
  • a typical recommended daily dosage regimen for oral administration should be in the range of about lmg to about 500 mg per day, preferably about lmg to about 20 O mg per day. These can be administered in 2 to 4 divided doses.
  • the present invention includes a therapeutically effective amount of at least one compound, or a pharmaceutically acceptable salt of the compound or a solvate of the compound, and a pharmaceutically acceptable carrier, excipient or diluent.
  • a kit comprising the agent is also provided.
  • Such a kit may include the above components in one or more containers within the kit.
  • specific forms of cosmetics to which the compound is added include, for example, liquid, milky, cream, lotion, ointment, gel, aerosol, mousse and the like. it can.
  • Lotions can be produced according to conventional methods using, for example, cosmetic additives such as suspending agents, emulsifying agents, preservatives and the like.
  • the dose of the cosmetic product varies depending on the age, sex, weight, disease level, type of composition of the present invention, dosage form, etc. of the patient to be administered. lmg to about 5 O mg may be administered.
  • the daily dose can be administered once or divided into several times.
  • the food ingredients to which the additive is added Physical forms include, for example, powders, tablets, beverages, mixed liquids with ingestible gels or syrups, such as seasonings, Japanese confectionery, Western confectionery, ice confectionery, beverages, spreads, pastes, pickles, canned bottles, Processed livestock products, fish meat 'fishery products', processed milk / eggs, processed vegetables, processed fruits, processed cereals, etc. It can also be added to feed and feed for domestic animals, poultry, bees, cormorants, fish and other domestic animals.
  • the dose varies depending on the age, sex, weight, disease level, type of composition of the present invention, dosage form, etc., but is usually about 0.1 lm g to about 50 Omg should be administered.
  • the above-mentioned daily dose can be administered once or divided into several times.
  • Example 1 Example 1 1 1-1 1 6 describes the synthesis of this compound.
  • Resorcinol 0.68 g and ethyl 2-benzyl-4,4,4-trifluoro-3-oxobutanoate (see WO 96/12706) 1.7 25 g of a solution of 7 O g of trifluoroacetic acid under reflux Stir for hours.
  • the reaction solution was concentrated under reduced pressure, and the resulting residue was subjected to Siri-force gel force ram chromatography to obtain 0.22 g of a pale yellow crystal of the coumarin compound of Compound No. (6).
  • the reaction conditions are as follows: 95 ° C for 5 minutes, 95 ° C for 30 seconds, then 59 ° C for 1 minute, then 72 ° C for 45 seconds for 30 cycles. Keep warm for a minute.
  • the obtained PCR product was subjected to agarose gel electrophoresis, and about l.lkb of DNA was recovered.
  • the expression vector pcDNA3.1 / Hyg was digested with the restriction enzyme Hindlll (Even Caravaio), then treated with T4 DNA P o y y rase (DNA Blunting Kit, Eigacar Bio) and the ends were digested. Smoothed.
  • the approximately 1.1 kb DNA obtained above and the linearized expression vector were mixed and ligated using T 4 DNA Ligase (DNA Ligation Kit Ver.2. It was introduced into a DH5 combi- tive cell (Yu-Kakara Bio). From the obtained transformant, a human type 3 17) 3-hydroxysteride dehydrogenase expression plasmid was obtained.
  • the nucleotide sequence of the DNA cloned into the plasmid is the human type 1 17 ⁇ -hydroxysteride dehydro disclosed in GenBank, which is the official database, under the registration number U0 5 6 5 9 It was consistent with the corresponding nucleotide sequence of the genase gene.
  • HeLa cells 1.6xl0 6 cells suspended in D-MEM medium containing 10% FCS 10 mL of cell suspension is spread on a cell culture dish with a diameter of 10 cm and allowed to stand for 20-24 hours in a C0 2 incubator overnight. did .
  • Transfer DNA reagent PolyFect Tra ns f ect ion Reagent (Qiagen) was added, mixed by pipetting 5 times, and allowed to stand at room temperature for 10 minutes.
  • Evaluation was performed by adding androstenedione to HeLa cells transiently expressing human type 3 17) 3-hydroxysteroid dehydrogenase and measuring the concentration of testosterone produced by conversion.
  • HeLa cells introduced with the human 3 type 17 / 3-hydroxysteroid dehydrogenase expression plasmid prepared in (2-2) were suspended in D-MEM medium containing 10 FCS.
  • the resulting cell suspension 96 ⁇ El plate LXL O 4 cells (100 L) was added per Ueru was allowed to stand at 20-24 hours C0 2 incubator. After standing, the medium was extracted, and 80 L of FCS-free medium was newly added.
  • the 1% DMS0 compound solution diluted with containing FCS-free medium was allowed to stand at 10 i L 30 min C0 2 incubator one added.
  • (1) to (7) and (9) to (11) has an enzyme inhibition rate of human type 3 17] 3-hydroxysteroid dehydrogenase at a concentration of 10 ⁇ . More than 80%.
  • the compound (8) represented by compound number (8) had an enzyme inhibition rate of 70% or more of human type 3 17
  • composition or the like for treating or preventing male hormone-dependent diseases is developed by inhibiting the activity of type 3 17-hydroxysteroid dehydrogenase and suppressing the enhancement of male hormone activity in tissues.
  • Oligonucleotide primers designed to amplify the human type 3 17-hydroxysteride dehydrogenase gene designed to amplify the human type 3 17-hydroxysteride dehydrogenase gene

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  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Dermatology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne une composition d'inhibition de la 17β-hydroxystéroïde déhydrogénase de type 3 caractérisée en ce qu'elle comprend un composé de coumarine représenté par la formule (I) ou son analogue, un support inerte et autres.
PCT/JP2008/066484 2007-09-05 2008-09-05 Composé de coumarine et son utilisation Ceased WO2009031706A1 (fr)

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JP2007-229984 2007-09-05

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012174488A2 (fr) 2011-06-15 2012-12-20 Nono, Inc. Agents et méthodes de traitement de maladies ischémiques et d'autres maladies

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011098893A (ja) * 2009-11-04 2011-05-19 Sumitomo Chemical Co Ltd テストステロンの生合成を抑制するための化合物の使用およびその化合物

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