EP0876378A1 - DERIVES DE 3,4-DIHYDRO 1,2,4]THIADIAZINO 3,4-b]BENZOTHIAZOLE, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANT - Google Patents
DERIVES DE 3,4-DIHYDRO 1,2,4]THIADIAZINO 3,4-b]BENZOTHIAZOLE, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANTInfo
- Publication number
- EP0876378A1 EP0876378A1 EP96939978A EP96939978A EP0876378A1 EP 0876378 A1 EP0876378 A1 EP 0876378A1 EP 96939978 A EP96939978 A EP 96939978A EP 96939978 A EP96939978 A EP 96939978A EP 0876378 A1 EP0876378 A1 EP 0876378A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formula
- compounds
- preparation
- ethyl
- radical
- 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.)
- Withdrawn
Links
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).
Landscapes
- 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)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9514241 | 1995-12-01 | ||
FR9514241 | 1995-12-01 | ||
PCT/FR1996/001868 WO1997020850A1 (fr) | 1995-12-01 | 1996-11-26 | DERIVES DE 3,4-DIHYDRO[1,2,4]THIADIAZINO[3,4-b]BENZOTHIAZOLE, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANT |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0876378A1 true EP0876378A1 (fr) | 1998-11-11 |
Family
ID=9485070
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP96939978A Withdrawn EP0876378A1 (fr) | 1995-12-01 | 1996-11-26 | DERIVES DE 3,4-DIHYDRO 1,2,4]THIADIAZINO 3,4-b]BENZOTHIAZOLE, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANT |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0876378A1 (ja) |
JP (1) | JP2000501407A (ja) |
AU (1) | AU7699596A (ja) |
WO (1) | WO1997020850A1 (ja) |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2678619B1 (fr) * | 1991-07-04 | 1993-09-17 | Rhone Poulenc Rorer Sa | Derives de 1,2,4-thiadiazolo[3,4-b]benzothiazole, leur preparation et les medicaments les contenant. |
-
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)
Title |
---|
See references of WO9720850A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO1997020850A1 (fr) | 1997-06-12 |
AU7699596A (en) | 1997-06-27 |
JP2000501407A (ja) | 2000-02-08 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19980514 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU NL PT SE |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19990601 |
|
RTI1 | Title (correction) |
Free format text: 3,4-DIHYDRO 1,2,4 THIADIAZINO 3,4-B BENZOTHIAZOLE DERIVATIVES, PREPARATION THEREOF AND DRUGS CONTAINING SAME |