Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
  • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
  • C07D513/04—Ortho-condensed systems
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
  • A61P25/16—Anti-Parkinson drugs

Definitions

• the present invention relates to new compounds of formula:
• R represents a polyfluoroalkyl radical
• R- represents an alkyl radical
• Hal represents a halogen atom
• radicals and the alkyl portions contain 1 to 4 carbon atoms in a straight or branched chain.
• the polyfluoroalkyl radicals are preferably the trifluoromethyl, trrfluoro-2,2,2 ethyl and pentafluoroethyl radicals.
• the compounds of formula (I) can be in the form of racemics, enantiomers or diastereoisomers. These compounds are also part of the invention
• the compounds of formula (I) can be prepared by cyclization of a compound of formula.
• R and R-j have the same meanings as in formula (I).
• This cyclization is generally carried out in an oxidizing medium (bromine, iodine potassium triiodide, hydrogen peroxide for example), or in the presence of chloramine T (sodium salt of N-chloro-p.toluenesulfonamide), in an inert solvent such as an alcohol (methanol, ethanol for example), a chlorinated solvent (chloroform, methylene chloride for example), a aromatic solvent (benzene, toluene for example), a ketone (acetone for example), at a temperature between -30 ° C and the boiling temperature of the reaction medium.
• an oxidizing medium bromine, iodine potassium triiodide, hydrogen peroxide for example
• chloramine T sodium salt of N-chloro-p.toluenesulfonamide
• an inert solvent such as an alcohol (methanol, ethanol for example), a chlorinated solvent (chloroform, methylene chloride for example), a aromatic solvent
• the compounds of formula (I), their racemics, enantiomers and diastereoisomers can be purified by the usual known methods, for example by crystallization, chromatography or extraction.
• the compounds of formula (I) have interesting pharmacological properties. These compounds are useful for the treatment of PARKINSON disease and parkinsonian syndromes.
• the activity of the compounds of formula (I) has been demonstrated in mice by measuring the reduction in the dopamine level of the st ⁇ atum induced by MPTP compared with that of the control animals.
• the coefficient of efficacy of each compound is calculated by the ratio [dopamine level of the MPTP group + product to be tested] / [dopamine level of the MPTP group].
• the compounds of formula (I) have an efficiency coefficient greater than 1.80.
• the compounds of formula (I) have a low toxicity. Their LD50 is greater than 50 mg / kg by the IP route in mice.
• the medicaments consist of at least one compound of formula (I), in the pure state or in the form of a composition in which it is associated with any other pharmaceutically compatible product, which may be inert or physiologically active
• the medicaments may be used orally or parenterally.
• compositions for oral administration tablets, pills, powders (gelatin capsules, cachets) or granules can be used.
• the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, saccharose, lactose or silica, under a stream of argon.
• inert diluents such as starch, cellulose, saccharose, lactose or silica
• These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a colorant, a coating (dragees) or a varnish
• liquid compositions for oral administration it is possible to use solutions, suspensions, emulsions, syrups and pharmaceutically acceptable elixirs containing inert diluents such as water, ethanol, glycerol, 3 vegetable oils or l 'paraffin oil.
• inert diluents such as water, ethanol, glycerol, 3 vegetable oils or l 'paraffin oil.
• These compositions can include substances other than diluents, for example wetting products, sweeteners, thickeners, flavorings or stabilizers.
• the sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions.
• solvent or vehicle water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other organic solvents can be used. suitable.
• These compositions can also contain adjuvants, in particular wetting agents, iso ⁇ tonics, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating into the composition of the sterilizing agents, by irradiation or by heating.
• compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semisynthetic glycerides or polyethylene glycols.
• compositions for topical administration can be, for example, creams, lotions, mouthwashes, nasal drops or aerosols.
• the doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally between 50 and 400 mg per day orally for an adult with unit doses ranging from 25 to 200 mg of active substance.
• the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.
• Tablets containing 50 mg of active product having the following composition are prepared according to the usual technique:
• capsules containing 50 mg of active product having the following composition are prepared:
• a solution for injection containing 10 mg of active product having the following composition is prepared:
• the invention also relates to a method of treating a mammal and, in particular a man, presenting with PARKINSON disease or parkinsonian syndromes comprising the administration of an effective amount of a compound of formula (I).

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• Health & Medical Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Neurosurgery (AREA)
• Medicinal Chemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Psychology (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (3)

Publications (1)

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• 1996
  • 1996-11-26 JP JP9521026A patent/JP2000501407A/ja active Pending
  • 1996-11-26 AU AU76995/96A patent/AU7699596A/en not_active Abandoned
  • 1996-11-26 EP EP96939978A patent/EP0876378A1/fr not_active Withdrawn
  • 1996-11-26 WO PCT/FR1996/001868 patent/WO1997020850A1/fr not_active Application Discontinuation

Non-Patent Citations (1)

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