WO1998022432A1 - Derives d'acylanilide a substitution acylamino ou composition comprenant ces derives - Google Patents
Derives d'acylanilide a substitution acylamino ou composition comprenant ces derives Download PDFInfo
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- WO1998022432A1 WO1998022432A1 PCT/JP1997/004174 JP9704174W WO9822432A1 WO 1998022432 A1 WO1998022432 A1 WO 1998022432A1 JP 9704174 W JP9704174 W JP 9704174W WO 9822432 A1 WO9822432 A1 WO 9822432A1
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07C255/60—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
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- C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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Definitions
- the present invention relates to a novel acylamino-substituted acylylanilide derivative, a salt thereof, and a pharmaceutical composition useful as an antiandrogen drug.
- Androgen a steroid hormone, is secreted from the testis and adrenal cortex and causes male hormones. Androgen is taken up into target cells and binds to the androgen receptor in the nucleus, and the androgen-bound receptor forms a dimer. This dimer binds to the androgen-response element on the DNA. to promote the synthesis of m RNA, by inducing protein responsible for androgen action, to express various actions in vivo (Prostate Suppl.45-51 (1996)) c androgens in disease to be ⁇ factor These include prostate cancer, benign prostatic hyperplasia, androgenesis, hirsutism, baldness, acne, seborrhea, etc. c Antiandrogens suppress the activation of androgen transcription and block the action of androgens Therefore, it is useful as a therapeutic agent for diseases in which these androgens are exacerbating factors.
- Antiandrogens are classified into compounds having a steroid skeleton similar to a substrate (steroidal antiandrogens) and compounds having a nonsteroidal skeleton (nonsteroidal antiandrogens ij).
- flucamide Japanese Patent Laid-Open No. 49-81332
- C- flutamide itself does not have an anti-androgenic effect.
- the carbon atom directly linked to the carbonyl group by metabolism ⁇ carbon It is known that the substitution of a hydroxyl group with an atom results in the formation of hydroxyflutamide, which exerts its activity, and this hydroxyl group is considered to be indispensable for the expression of antiandrogen action (J. Med. Chem 31, 954-959 (1988)).
- bicalutamide (GB 8, 221 and 421) has already been described in various countries, and GB 8, 221 and 42] shows that the acyl portion of an acylanilide derivative has aryl (or heteroaryl) sulfonyl ( Or an acylanilide derivative, such as an alkanol substituted with a sulfinyl or thio) aryl (or heteroaryl) amino.
- the compounds substantially disclosed are, like hydroxyflutamide, all compounds having a hydroxyl group at the ⁇ - carbon atom.
- carbaminoaminoacetanilide derivatives include US Pat. No. 4,532,251, and 2,6-dizino substituted with a bilazinyl carbonyl group or a substituted imidazolyl carbenyl group.
- Ricinamide has been disclosed as a fungicide. However, these compounds are
- An object of the present invention is to provide a novel acylamino-substituted acylylanilide derivative and a salt thereof, which have a strong antiandrogenic action and have less of these side effects, and further provide a drug containing the same. . Disclosure of the invention
- the present inventors have conducted intensive studies to solve these problems associated with existing antiandrogens, and surprisingly, an acylylamide derivative substituted with an acylamino group has been required for the expression of activity.
- the present invention has been found to be a compound having strong oral activity and antiandrogenic activity without having a hydroxyl group of ⁇ -carbon atom, further having few side effects, and having good oral activity. Was completed.
- the present invention relates to an acylamino-substituted acylylanilide derivative represented by the following general formula (I) or a salt thereof.
- R 1 and R 2 same or different, halogen atom, cyano, halogeno lower alkyl, nitro, carboxyl, lower alkanoyl or lower alkoxycarbonyl group
- R 3 hydrogen atom or lower alkyl group
- R 4 , R 5 , RG and R 7 identical or different, hydrogen atoms, lower alkyls which may be substituted, or heteroatoms in which R 4 and R 5 are in the form of May form a cycloalkyl group, or when n is 1, R 5 and R 6 may form a cycloalkylene group,
- a and A 2 Same or different binding or low S
- R 8 a hydrogen atom, a hydroxyl group, a lower alkoxy, or a combination of R 8 and R 5 may form a nitrogen-containing cycloalkylene group;
- R 7 and R 8 may be combined to form a nitrogen-containing cycloalkylene group:
- R 4 and R 5 represents a group other than a hydrogen atom.
- Y represented by the formula: s1 — s— or — C—N—
- R 9 lower alkyl, cycloalkyl, or aryl which may have a substituent, aralkeninole, aralkyl, or aryloxy lower alkyl, or a heteroaryl group which may be condensed with a benzene ring
- R 10 hydrogen atom or lower alkyl group
- X 2 oxygen atom or sulfur atom
- R 4 and R 5 represents a group other than a hydrogen atom: :), or an acylamino-substituted acylylanilide derivative or a salt thereof; Consists of halogen atoms, hydroxyl groups, lower alkoxy, lower alkanoyloxy, halogeno lower alkyl groups having one or more substituents of the lower alkyl group or aralkyl group of R 4 or R 5 , R "and R T A substituent selected from the group consisting of R 9 : aryl, aralkenyl, aralkyl or aryloxy lower alkyl, or benzene
- the substituent of the heteroaryl group which may be condensed with a ring is one or more of the same or different halogen atoms, hydroxyl groups, halogeno lower alkyl, lower alkyl, lower alkoxy, halogeno lower
- n is 0 and R 4 or R 5 is the same or different and is a hydrogen atom, or one or more of the same or different substituents is a hydroxyl group, lower alkoxy, lower alkanoyloxy, halogeno lower alkyl group.
- the present invention also relates to a pharmaceutical composition containing an acylamino-substituted acylylanilide derivative or a pharmaceutically acceptable salt thereof as an active ingredient, in particular, a pharmaceutical composition which is an antiandrogen, especially for prostate cancer and prostatic hyperplasia.
- a pharmaceutical composition which is an agent for preventing or treating masculosis, hirsutism, baldness, acne, and seborrhea.
- lower means a straight or branched carbon chain having 1 to 6 carbon atoms.
- An aryl group which may have a substituent, an aralkenyl group, an aralkyl group, a heteroaryl group which may be condensed with a benzene ring, or an aryloxy lower alkyl group has 1 to 3 substituents on the ring.
- halogen atom a halogeno lower alkyl group, a lower alkyl group, a lower alkoxy group, a halogeno lower alkoxy group, a cyano group, a nitro group, a lower alkyl group, a hydroxyl group, a phenyl group, a monoalkyl group.
- the substituent of “substituted or substituted, lower alkyl group or aralkyl group” may be one or more identical or different substituents.
- the group is selected from the group consisting of hydroxyl, lower alkoxy, lower alkanoyloxy, and halogeno lower alkyl:
- “Lower alkyl group” means a straight or branched lower alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl, isoflurane, n-butyl, isobutyl, sec-butyl, ten-butyl. —Butyl, n-pentyl, n-hexyl, etc. ⁇ 3 lower alkyl groups are preferred ⁇ ,
- lower alkylene group refers to a linear or branched lower alkylene group having 1 to 6 carbon atoms, such as methylene, ethylene, propylene, isobutylpyrene, butylene, pentamethylene, hexamethylene and the like. Preferred are lower alkylene groups having 1 to 3 carbon atoms, and more preferably methylene.
- Alkyl group means "aryl-1 lower alkylene-1”.
- Alkyloxy group means "aryl-1 lower alkylene-1-”.
- Alukeniru group means "Ariru one lower alkenylene one", preferably C 6 - a 10 Ariru one C. _ 6 alkenyl group, phenylene Rueparu, Fueniruburo Bae alkenyl, naphth / Reeteyuru, Nafuchirupuro Bae alkenyl such as Is mentioned.
- Aryloxy lower alkyl group means “aryl-O-lower alkylene-”.
- “Lower alkanoyloxy noisy Rua amino group” of the "lower Arukiru - C (two O) - NR 1 1 -” means, R '' represents a water atom or a lower Arukiru group: -:
- Halogen atom includes, for example, fluorine, chlorine, bromine or iodine atom
- Halogeno-lower alkyl group of the lower Arukiru groups of the C, "6 Arukiru group i this the Bruno nuclear ⁇ - is 3 or obtained by replacing, triflumizole Ruo b preferably methyl ::
- Halogeno lower alkoxy group means “halogeno lower alkyl mono-”
- Acyl group means a broadly defined acyl group, meaning carbonyl and sulfonyl derivatives:
- “Cycloalkyl group” means a 3- to 8-membered saturated hydrocarbon ring, preferably 3 to (member)
- Cycloalkylene group is a bond of the above cycloalkyl
- “Mono or di-lower alkylamino group” means an amino group in which the lower alkyl group is substituted by 1 or 2 groups.
- R 4 and R 5 gar body and turned by cycloalkyl group which may contain a hetero atom the cycloalkyl containing carbon atom bonded to R 4 and R 5 and them as ring atoms —
- the ring contains one heteroatom selected from nitrogen, oxygen, and sulfur.
- hetero atom for example, a sulfur atom is substituted with one or two oxo groups and
- heteroatom is preferably an oxygen atom, the concrete include Okisaniru.
- And n is a R 5 and R 6 gar body case 1, to form a cycloalkylene group" and includes a carbon atom bonded to R 5 and R 6 and its those as ring atoms It means forming the above cycloalkylene.
- Heteroaryl group optionally condensed with a benzene ring means 5 or (containing a heteroaryl group or benzene containing 1 to 3 heteroatoms selected from nitrogen, oxygen or sulfur atoms.
- a heterocyclic aryl fused with a ring, and the heteroaryl includes bilol, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, triazole, thiophene, thiopyran, furan, pyran, dioxolan, thiazole, Isothiazole, thiadiazole, Examples include azine, oxazole, isoxazole, oxaziazole, furazane, dioxazole, oxazine, oxazineazine, dioxazine, and the like.
- nitrogen-containing heteroaryl fused to a benzene ring examples include indole, isoindole, quinoline, isoquinoline, benzothiophene, and benzothiazolone.
- benzofuran, benzofurazan and the like preferably, pyridine, p : limidine, indole, quinoline, thiophene, furan and the like ::
- R 8 and R together form a nitrogen-containing cycloalkylene group or "When n is 1, R 7 and R 8 together form a nitrogen-containing cycloalkylene group” are defined as ring atoms R 8 and the 5- to 7-membered nitrogen-containing cycloalkane, or a ring atoms containing a carbon atom to which nitrogen atom and R 5 being substituted is substituted is substituted with R 8 les, Ru nitrogen atom and R 7 There substituting means to form a 4 to 7-membered nitrogen-containing cycloalkane containing Les, Ru carbon atoms and a 2, specifically pyrrole, piperidine, Kisahidoro Azepin the like to 2, Pyrrole or Pyridine is preferred ⁇ :
- the compound having a tertiary amine may be oxidized with respect to the amine, and includes all oxidized derivatives thereof.
- the compound (I) of the present invention has a tautomer based on an amide bond .
- the compound (I) may have one or more asymmetric carbon atoms.
- isomers such as (S) isomers, racemic forms, diastereomers, etc. :: Also, depending on the type of substituent, there may be a double bond, (Z) form, (E) form
- the compound having a ring may have cis-trans.
- the present invention includes all separated or mixed forms of these isomers.
- the compound of the present invention forms a salt.
- the acid addition salts with inorganic or organic acids there have is a salt with an inorganic or organic bases
- Le Shi pharmaceutically acceptable salt is preferred ⁇ : is a salt thereof , Specifically, mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid or phosphoric acid, or formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, Addition salts with organic acids such as lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid or toluenesulfonic acid, or acidic amino acids such as aspartic acid or glutamic acid, sodium, Inorganic bases such as potassium, magnesium, calcium, aluminum, and lithium; organic bases such as methylamine, ethylamine
- the quaternary ammonium salt is specifically an ammonium salt obtained by reacting with a lower alkyl halide, a lower alkyl triflate, a lower alkyl tosylate or a benzyl halide, and preferably a salt with a methinoyl or benzyl chloride.
- the compound of the present invention can form a hydrate, a solvate with ethanol or the like, or a crystalline polymorph.
- the present invention includes all of these hydrates, solvates or crystalline polymorphs separated or mixed compounds :
- the compound (I) of the present invention can be produced by applying various production methods: The typical production methods are described below.
- This production method comprises the steps of amidating a substituted ⁇ -salt represented by the general formula (II) with a carboxylic acid or a reactive derivative or a thio-acid or a reactive derivative thereof represented by the general formula (in) to protect the compound.
- This is a method for producing the compound (I) of the present invention by removing the protecting group when having a group.
- Examples of the reactive derivative of the compound (III) include ordinary esters such as methyl ester, ethyl ester, isobutyl ester, and tert-butyl ester of carboxylic acid; acid chlorides such as acid chloride and acid bromide; acid azide; Active esters, symmetrical acid anhydrides, alkyl carbonate halides, etc., obtained by reacting with phenolic compounds such as 4-dinitrophenol and N-hydroxyamines such as I-hydroxysuccinimide and I-hydroxybenzotriazole Reaction with an organic acid-based mixed acid anhydride, diphenylphosphoryl chloride, N-methylmorpholine obtained by reacting with halocarbonic acid alkyl ester or bivaloyl halide, or triphenylphosphoric acid
- Active esters of organic origin include:
- the reaction varies depending on the reactive derivative used and the condensing agent, but is usually halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform, aromatic hydrocarbons such as benzene, toluene and xylene, polyester, and the like.
- Inert organics such as ethers such as tetrahydrofuran, esters such as ethyl acetate, acetonitrile, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone and dimethyl sulfoxide.
- the reaction is performed in a solvent, under cooling, under cooling to room temperature, or at room temperature to heating.
- oxygen, sulfur, nitrogen, etc. present in the molecule be bonded to a protecting group, and such a protecting group is described in Greene and Wuts, "Protective Groups in Organic.” And the like.
- the protecting groups described in “Synthesis” 2nd edition can be used, and these can be used and divided appropriately according to the reaction conditions.
- This production method comprises the steps of: (a) adding a substituted amine represented by the present compound (IV) or a salt thereof to a carboxylic acid or a reactive derivative thereof, a sulfonic acid or a reactive derivative thereof, thiocarboxylic acid or a reactive derivative thereof To produce the compound (1) of the present invention by using the same reaction conditions as in the first production method:
- the reaction varies depending on the reactive derivative used and the condensing agent, but is usually halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform, aromatic hydrocarbons such as benzene, toluene, xylene, ether, tetrahydrofuran, etc.
- halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform
- aromatic hydrocarbons such as benzene, toluene, xylene, ether, tetrahydrofuran, etc.
- organic solvent inert to the reaction of ethers such as ethers, esters such as ethyl acetate, and N, N-dimethylformamide N, N-dimethylacetamide, dimethyl sulfoxide, etc.
- the compound (IV) of the present invention was used in excess, or N-methylmorpholine, trimethylamine, triethylamine, N, N-dimethylaniline, pyridine, 4- (N, N-dimethylamino) pyridine, bicholine,
- a base such as lutidine
- Pyridine etc. can be used as a solvent.
- the amide group represented by the compound (la) of the present invention is converted to a thioamide group to produce the compound (lb) of the present invention.
- This reaction can be prepared by any of the known chemical methods for synthesizing thioamide derivatives from amide derivatives such as dipentapentasulfide and Lawesson's reagent:
- the reaction is usually carried out with halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as ether and tetrahydrofuran, esters such as ethyl acetate and pyridine.
- halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform
- aromatic hydrocarbons such as benzene, toluene and xylene
- ethers such as ether and tetrahydrofuran
- esters such as ethyl acetate and pyridine.
- organic solvent inert to the reaction Rejected performed under cooling to room temperature, or at room temperature to heating
- hydrolysis, hydrogenation, ureidation, etc. are also carried out by ordinary methods.
- the compound of the present invention thus produced can be isolated and purified as a salt, a hydrate, a solvate, or a polymorphic substance of the compound of the present invention as it is free.
- Salt can also be produced by subjecting it to a conventional salt formation reaction.
- the starting compound of the above-mentioned production method may contain a novel substance, it may be produced by applying the production method described in Reference Example, a method analogous to the production method, or a modified method arbitrarily practicable by those skilled in the art. it can. Isolation and purification are performed by applying ordinary chemical procedures such as extraction, concentration, distillation, crystallization, filtration, recrystallization, and various types of chromatography:
- various isomers can be separated by utilizing the difference in physicochemical properties between isomers. For example, by optical isomers selecting appropriate raw materials, or by racemic resolution method of racemic compounds, the availability of the c industry that can be force S lead to stereochemically pure isomers
- the compound of the present invention has a strong anti-androgenic effect by suppressing the transcriptional activation by androgen, and is a compound having few side effects such as central action and agonist action.
- the compound of the present invention is useful as a therapeutic or prophylactic agent for diseases in which androgen is involved as an adverse factor, for example, prostate cancer, prostatic hypertrophy, virilization, hirsutism, baldness, acne, seborrhea and the like. is there.
- the usefulness of the compound of the present invention has been confirmed by the following test methods! RU
- CHO cells were seeded on a 100-mm-diameter cell culture dish with 10 6 IX cells, and 12 to 18 hours later, a human androgen receptor expression plasmid co-precipitated with calcium phosphate, MMTV-LTR
- the luciferase jelly boater plasmid (including the neomycin resistance gene) was added and transfection was performed. After 15 hours, the medium was removed, the cells were diluted in several steps, and replated, and the medium was fed with GENETICIN® (neomycin) to a final concentration of 500 ⁇ g / ml .: About 1 week later, the cells were selected by neomycin.
- the isolated cells were detached, and cells expressing the human androgen receptor expression gene, MMTV-luciferase revoter-gene, constitutively expressing and isolated by the limiting dilution method (CHO / MMTV stable transformant:
- SV40 reporter gene stable transformant was obtained in the same manner as described above. However, the SV40 reporter plasmid and the neomycin resistance gene expression plasmid were simultaneously transfected (CHO / SV40 stable transformant; ⁇
- CHO / MMTV stable transformant cells and CHO / SV40 stable transformant cells were seeded at 1 ⁇ 10 4 cells / well in a luminobure 1 for% well cell culture, and the compound of the present invention was added 6 to 8 hours later. 18 minutes after compound addition, add 20 ⁇ l of a solution containing 1% Triton-X and 10% glycerol to lyse the cells, add 100 ⁇ l of luciferase substrate solution containing 0.47 mM luciferin, and use a luminometer. The luminescence was measured and these were taken as the luciferase activities obtained by MMTV-LTR transcriptional activation by the human androgen receptor and non-specific SV40 flow motor transcriptional activation:
- the transcription activation effect of the compound of the present invention was calculated by the following formula as a ratio to the transcription activity induced by InM DHT.
- CHO / MMTV stable transformant cells and CHO / SV40 stable transformant cells were seeded at 1 ⁇ 10 4 cells each in a luminoblate for% well cell culture, and after 6 to 8 hours, simultaneously with DHT (final concentration 0.3 nM).
- the compound of the present invention was added. Eighteen hours after the addition of the compound, the cells were lysed by adding 20 ⁇ l of a solution containing 1% Triton-X and 10% glycerol, and 100 ⁇ l of a luciferase substrate solution containing 0.47 mM luciferin was added, followed by luminescence using a luminometer. Measure the amount Luciferase activity obtained by MMTV-LTR transcriptional activation by human androgen receptor and non-specific SV40 promoter transcriptional activation:
- the inhibitory effect on transcriptional activation by the compound of the present invention was calculated by the following formula as the inhibition rate against the transcriptional activity induced by 0.3 nM DHT.
- Inhibition rate (%) 100 (1'- ⁇ ') / ( ⁇ - ⁇ )
- the IC 50 was determined from the concentration of the compound of the present invention at which the inhibition rate calculated by the above method was 50%.
- the activity of the compound of the present invention determined by the above a) and b) is shown below:
- Three-week-old male Wistar rats were simultaneously administered testosterone propionate and the compound of the present invention once a day for 5 consecutive days from 72 hours after castration. Six hours after the final administration, the wet weight of the ventral prostate was measured, and the inhibitory effect of the compound of the present invention on the increase in prostate weight by testosterone propionate was examined.
- Testosterone propionate was dissolved in cottonseed oil containing 5% ethanol and subcutaneously administered at a dose of 0.5 mg / kg body weight of the rat : the compound of the present invention was orally administered in a 0.5% methylcellulose solution ::
- the prostate weight increase inhibitory effect of the compound of the present invention was as follows: test group in which testosterone flobionate and the compound of the present invention were administered together, test group in which testosterone propionate alone was administered, and control group, and no testosterone propionate and the compound of the present invention.
- Androgen is a compound useful as a therapeutic agent for the prevention and treatment of diseases associated with exacerbation factors
- Preparations containing one or more of the compound of the present invention or a salt thereof as an active ingredient are prepared using carriers, excipients and other additives that are usually used for preparation.
- the drug can be administered orally in the form of tablets, pills, capsules, granules, powders, liquids, etc., or injections such as intravenous and intramuscular injections, and parenteral administrations such as suppositories and transdermals.
- l OOOmg about 1 to 100 mg, preferably 0.1 to 100 mg per adult for parenteral administration per day (). 1 to 100 mg, preferably about 0.001 to 50 mg, divided into 1 dose or 2 to 4 doses
- the one or more active substances include at least one inert diluent such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, metasilicate.
- inert diluent such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, metasilicate.
- the composition is formulated according to the usual practice with additives other than inert diluents, such as lubricants such as magnesium stearate and disintegrants such as calcium cellulose dalcholate.
- Tablets or pills may contain sucrose, gelatin, hydroxypropylcellulose, hydroxypro as required, including stabilizers such as lactose and solubilizing agents such as glutamic acid or aspartic acid.
- -Sugar coatings or gastric-soluble coatings such as ⁇ may be coated with a film of enteric substance:
- Liquid compositions for oral administration include pharmaceutically acceptable emulsifiers, solutions, suspensions, tablets, elixirs and the like, and are generally inert diluents such as purified water. Contains: In addition to the inert diluent, this composition may contain adjuvants such as wetting agents, suspending agents, sweetening agents, flavoring agents, flavoring agents, preservatives, :
- Injections for parenteral administration include sterile aqueous or non-aqueous solutions ij, aqueous solutions including suspensions and emulsions, and suspensions include, for example, distilled water for injection and physiological saline. Contains saline.
- Non-aqueous solutions and suspensions for example blanking: b propylene glycol, Boriechiren glycolate Ichiru, vegetable oils such as Oribu oil, alcohols such as ethanol, Borisorubeto 80.
- compositions may contain adjuvants such as preservatives, wetting agents, emulsifiers, dispersants, stabilizers (eg, lactose), and solubilizing agents (eg, glutamic acid, aspartic acid).
- adjuvants such as preservatives, wetting agents, emulsifiers, dispersants, stabilizers (eg, lactose), and solubilizing agents (eg, glutamic acid, aspartic acid).
- Reference Example 1 52 2- (4-Trifluoromethylbenzoylamino) 2-methylpropanoate Methyl Reference Example 1-62 2- (4-Funolei Lof :: Nylsulfonylamino 2-Methylpropanoate Reference Example 1-72 2- (4-Nitrophenylsulfonylamino) methyl 2-methylpropanoate Reference Example 1-82--(4-Methoxyphenylsulfonylamino) 2-methylpropanoate Reference Example 1-93 -(4-Funolelov: Nylsulfonylamino) methyl methyl lobanoate
- REFERENCE EXAMPLE 1 15 1 (4-FUNORESHILOF ;: Nylsulfonylamino) cyclo 'methyl hexylcarboxylate Reference Example 1-16 1- (4-Fluorobe, zolylamino) cyclohexylcarboxy
- Reference Example 2-13 1- (4-Fluorophenylsulfonylamino) cyclopropylfuronic acid Reference Example 2—14— (4-1: boric acid Reference Example 2—15 1— (4-fluorophenylsulfonylamino) cyclopentylcarboxylic acid Reference Example 2—16 1— (4-funo ⁇ - Reference Example 2—17 (4-Fluorophenylsulfonylamino) cyclohexylcarboxylic acid g Reference Example 2-18 (4: no) cyclohexylcarboxylic acid
- Reference example 4 2 2 N-dioxy carbonylamino-N (4-cyano 3- -trifluoromethylphenyl) methylpropananilide
- reaction mixture was diluted with 50 ml of ethyl acetate, washed twice with 50 ml of distilled water, and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was subjected to silica gel column chromatography to obtain 0.63 g of the title compound from a fraction eluted with ethyl acetate (3: 7).
- Reference Example 1 The following Reference Example was synthesized in the same manner as 1-1.
- Example 2 16 It was synthesized in Example 2 16 in the same manner as in Example 1:
- the reaction solution was diluted with 50 ml of ethyl acetate, washed with 5 () ml of 1N hydrochloric acid, 50 ml of saturated aqueous sodium hydrogen carbonate and 50 ml of distilled water, and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was subjected to silica gel column chromatography and dissolved in ethyl acetate-hexane (17: 3). A crude crystal was obtained from the outlet. The crude crystals were recrystallized from ethyl acetate, and Example] 8-21 was synthesized in the same manner as in Example 3 of the title compound as colorless crystals.
- Examples 23 and 24 were synthesized in the same manner as in Example 1.
- Examples 26 to 33 were synthesized in the same manner as in Example 25-Examples 34 to 64 were synthesized in the same manner as Example 1.
- Phthanolamide 5 Dissolve Og in dichloromethane. Then, 6.37 ml of ethyl and chloroformate were added, and the mixture was stirred for 1 hour and further stirred at room temperature for 6 hours. The solvent was distilled off under reduced pressure, a mixed solvent of benzene and hexane was added, and the precipitated crystals were separated by filtration. Was distilled off to give 2-cyanobenzoic anhydride (58 mg).
- Examples 69-78 were synthesized in the same manner as in Example 68.
- Example 80 to 87 were synthesized in the same manner as in Example 79.
- Example 88
- Example 9 Examples 9] and 92 were synthesized as in Example 90:
- Example 94 was synthesized in the same manner as in Example 93.
- the organic layer was washed with saturated aqueous sodium bicarbonate solution (3 Oml), water (3 Oml), saturated aqueous citric acid solution (3) ml ⁇ 2, and dried over sodium sulfate.
- the solvent was distilled off under reduced pressure.
- the crystals were recrystallized from diisopropyl ether-ethyl acetate, and recrystallized from acetic acid acetate / lehi-fu / ro-lo'sole-hexane, to give 1 mg of the title compound as colorless crystals.
- Example 1 (X) —1 () 4 was synthesized in the same manner as in Example 25.
- Example 1 () 5-107 was synthesized in the same manner as in Example 1.
- Example 108 was synthesized in the same manner as in Example 25.
- Example K 9-11 11 was synthesized in the same manner as in Example 1.
- Examples 123 to 129 were synthesized in the same manner as in Example 1.
- Example 131 was synthesized in the same manner as in Example 130. : The structures and physical properties of these examples are shown in the table.
Abstract
La présente invention concerne des dérivés d'acylanilide à substitution acylamino représentés par la formule générale (I) ou certains de leurs sels. L'invention concerne également une composition pharmaceutique comprenant ces dérivés ou leurs sels. En l'occurrence, ces compositions, qui font preuve d'une activité antiandrogène, conviennent comme agent prophylactique ou thérapeutique dans le cas de cancer de la prostate, l'hypertrophie de la prostate, la déféminisation, l'hypertrichose, l'alopécie, l'acné, la séborrhée, et similaires, dans lesquels l'androgène interviennent comme facteur exacerbant.
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WO2022007903A1 (fr) * | 2020-07-09 | 2022-01-13 | 四川海思科制药有限公司 | Composé capable d'inhiber et de dégrader les récepteurs aux androgènes et compositions pharmaceutiques et leurs utilisations pharmaceutiques |
WO2022096542A1 (fr) | 2020-11-06 | 2022-05-12 | Boehringer Ingelheim International Gmbh | Dérivés de 2-[thiophén-2-yl)formamido]-n- (phényl)-2-méthylpropanamide et leur utilisation en tant que médicament |
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4981332A (fr) * | 1972-11-24 | 1974-08-06 | ||
US4532251A (en) * | 1982-12-03 | 1985-07-30 | Chevron Research Company | N-substituted-N',N'-disubstituted glycinamide fungicides |
-
1997
- 1997-11-17 WO PCT/JP1997/004174 patent/WO1998022432A1/fr active Application Filing
- 1997-11-17 AU AU49664/97A patent/AU4966497A/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4981332A (fr) * | 1972-11-24 | 1974-08-06 | ||
US4532251A (en) * | 1982-12-03 | 1985-07-30 | Chevron Research Company | N-substituted-N',N'-disubstituted glycinamide fungicides |
Non-Patent Citations (1)
Title |
---|
CHEMICAL ABSTRACTS, Vol. 101, 1984, Abstract No. 6764, VIEWEG H., "Synthesis of alpha-(Arylsulfonylamino)-Omega-Phenylalkyl carboxylic Acid 3- and -4-Amidinoanilides"; & PHARMAZIE, 1983, 38(12), 818-20. * |
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