Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/12—Ketones
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
  • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
  • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
  • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
  • A61K31/445—Non condensed piperidines, e.g. piperocaine
• • 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

Definitions

• the present invention relates to a therapeutic agent for nephritis, and more particularly to a therapeutic agent for nephritis containing a Fuunil derivative.
• nephritis steroidal and non-steroidal anti-inflammatory and anticoagulant drugs are used in certain types of nephritis, but no drug has been found that has a definite therapeutic effect on nephritis. Rest and diet are the mainstays of treatment, and the emergence of truly effective therapeutic agents is desired.
• the present inventors previously synthesized various novel funil derivatives and studied their pharmacological actions. As a result, they found that they had an excellent inhibitory effect on platelet aggregation, and filed a patent application (Japanese Patent Application No. 61-2682). 61-6091). As a result of further research, the present inventors have found that the below-mentioned funyl derivative has an effect of remarkably suppressing chronic nephritis in rats due to administration of bovine serum albumin (BSA), and completed the present invention. Disclosure of the invention
• the following therapeutic agents for nephritis are provided.
• R 1 and R 2 are the same or different and each represent a hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy lower alkyl group or a protecting group for a hydroxyl group; and R 3 represents a hydrogen atom or a lower alkoxy group.
• m represents an integer of 1 or 2
• Y represents an alkyl group, an aralkyl group, an alkoxy group, an aralkyloxy group, or a compound represented by the formula ( ⁇ )
• R 2 is a hydrogen atom or a lower alkoxycarbonyl group.
• Y is an alkyl or alkoxy group having 1 to 20 carbon atoms.
• lower alkyl group means a linear or branched alkyl group having 1 to 4 carbon atoms, preferably methyl or ethyl. , Isopropyl, n-propyl and the like;
• lower alkoxy is a straight or branched alkoxy having 1 to 4 carbon atoms, preferably methoxy, ethoxy, isopropoxy, n-means propoxy and the like.
• hydroxyl protecting group means a group usually used for protecting a hydroxyl group in the field of synthetic organic chemistry.
• alkyl group or “alkoxy group” means a straight-chain or branched alkyl group or alkoxy group having preferably 1 to 20 carbon atoms, more preferably 7 to 15 carbon atoms.
• alkyl preferably means a phenylalkyl group having 1 to 5 carbon atoms in the alkyl moiety.
• the phenyl derivative having the above formula (I) used in the present invention is a novel compound. It is produced by the following method according to the type of the substitution component.
• the above reaction is produced by reacting with an alcohol or amine derivative represented by It is preferably carried out in a suitable solvent in the presence of a condensing agent such as ethyl carbonate chloride or N, If-dicyclohexylcarpoimide.
• a condensing agent such as ethyl carbonate chloride or N, If-dicyclohexylcarpoimide.
• the phenyl derivative (I) of the present invention is effectively used for the treatment of nephritis, particularly chronic nephritis, and the dose varies depending on the symptoms.
• the daily dose for adults 1 to: LOO Omg, preferably 10 to 500 It is recommended to be administered in 1 to 3 divided doses as needed, depending on the symptoms.
• the administration method can be in any form suitable for administration. In particular, oral administration is desirable, but intravenous injection is also possible.
• the compound of the present invention is used alone or as an active ingredient, alone or mixed with a pharmaceutical carrier or excipient in a usual manner, to prepare tablets, dragees, powders, capsules, granules, suspensions, It can be applied in various forms formulated into emulsions and injection solutions.
• carriers or excipients include calcium carbonate, calcium phosphate, starch, glucose, lactose, dextrin, alginic acid, mannitol, talc, magnesium stearate and the like.
• reaction solution was returned to room temperature, stirred overnight, added with a saturated aqueous ammonium chloride solution, added with water, and extracted with ethyl acetate.
• the ethyl acetate layer was washed with INH CJ TM and saturated saline, dried over sodium sulfate, and concentrated under reduced pressure.
• the obtained residue was recrystallized from 100 ml of ethanol to give 5-(3-methoxy-4-ethoxycarbonyloxyphenyl)-2,4-pentagenone. 50 g (59%) of the ethyl ester were obtained.
• Lactose 700 mg Corn starch 100 mg Production method: Compound VII powder passed through a 60-mesh screen, lactose passed through a 50-mesh screen, and corn starch passed through a 120-mesh screen are mixed with a V-type mixer to form a powder.
• Lactose 684 mg Maize starch 100 mg Hydroxypropyl cellulose 16 mg Formulation Compound VI powder passed through a 60 mesh sieve and lactose passed through a 50 mesh sieve and corn starch passed through a 120 mesh sieve After mixing with a V-type mixer, an aqueous solution of hydroxypropylcellulose was added, mixed with a twin-screw kneader, extruded and granulated, dried at 60 ° C, sized with an oscillator, and sized at 12 cm. Granules are those that pass through the mesh and do not pass through the 60 mesh.
• magnesium stearate 0.1% magnesium stearate is added to the granules of Example 2, mixed, and filled into No. 4 capsule.
• Raw material Prescription amount Compound 1 1 g Butyl paraoxybenzoate 0.05 g Propylene glycol 2.5 gr Polysorbate 80 2.5 g White petrolatum 93.45 s: Production method: Dissolve components other than white petrolatum at 60 ° C. Separately, dissolve white petrolatum at 70 ° C and cool both dissolving solutions while mixing them gradually to obtain an ointment.
• Raw material Prescription amount Compound W 50mg Witepsol 1650mg Production method-Melt at 60 C, stir with cooling, fill into aluminum foil using servac to make suppositories.
• Raw material Prescription amount Compound IX 5 mg Polysorbate 80 50 mg Water for injection 1 ml Production method Compound X is dissolved in Polysorbate 80, and then distilled water for injection is added to dissolve and disinfect. Aseptically fill the sample into an injection.
• a physiological saline containing bovine serum albumin (BSA) 2ing is administered subcutaneously to the neck of a 3-week-old male Fisher rat.
• BSA bovine serum albumin
• intravenous administration of saline containing BSA 2ing After collecting urine excreted on a single day and removing insoluble matter by centrifugation, the amount of urine and the amount of protein in the urine are measured with an absorptiometer using a urine protein measurement kit. The results are shown in Table 1.
• the Fuunil derivative (I) of the present invention showed a marked inhibitory effect on proteinuria, and an inhibitory effect on nephritis was also observed in pathological specimens. Further, it was confirmed that the Fuunyl derivative (I) according to the present invention, which is not shown in Table 1, also has a similar nephritis inhibitory effect.
• Fuyuniru derivative (I) of the present invention is any even lOOOfflg / kg or more, high safety in comparison with effective amount was confirmed.
• the phenyl derivative of the present invention is effectively used as a therapeutic agent for nephritis and used in the pharmaceutical industry.

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• Health & Medical Sciences (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Veterinary Medicine (AREA)
• Chemical & Material Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Epidemiology (AREA)
• Emergency Medicine (AREA)
• Bioinformatics & Cheminformatics (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Reproductive Health (AREA)
• Endocrinology (AREA)
• Urology & Nephrology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Hydrogenated Pyridines (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Applications Claiming Priority (2)

Publications (1)

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Cited By (4)

Citations (8)

• 1986
  • 1986-12-01 JP JP61284169A patent/JPS63139124A/ja active Granted
• 1987
  • 1987-12-01 WO PCT/JP1987/000932 patent/WO1988004169A1/ja unknown

Patent Citations (8)

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