Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
  • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
  • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
• • 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
• • 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
  • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• • 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
  • A61P25/22—Anxiolytics
• • 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
  • A61P25/24—Antidepressants
• • 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
  • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• • 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
  • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence

Definitions

• the subject of the present invention is compounds derived from 3- (benzofuran-5-yl) oxazolidin-2-one, their preparation process and their therapeutic application.
• R 1 represents a phenyl group, a phenylmethyl group, an alkyl group comprising 3 to 6 carbon atoms or a fluoroalkyl group comprising 1 to 6 carbon atoms
• R 2 represents a hydrogen atom or a methyl group.
• an alkyl group is an aliphatic group, saturated, linear or branched
• a fluoroalkyl group is an alkyl group as defined above, in which at least one of the carbon atoms is substituted by one or more fluorine atoms.
• a fluoroalkyl group according to the invention comprises 3 fluorine atoms substituted on the carbon atom at the end of the alkyl chain.
• the compounds of formula (I) have an asymmetric carbon atom. They can therefore exist in the form
• the invention includes pure enantiomers and mixtures thereof, including racemic mixtures.
• Preferred compounds of formula (I) are those for which (i) R 1 represents a phenyl group, a phenylmethyl group, a propyl group or a 3,3,3-trifluoropropyl group and / or (ii) R 2 represents a group methyl.
• the compounds of formula (I) can be prepared according to the process represented in scheme 1 in appendix, starting from a compound of formula (II)
• R 1 is defined as in formula (I).
• This process consists in reducing the nitro group of the compound of formula (II), in reacting the compound of formula (III))
• the compounds of formula (II) can be prepared according to the process represented in scheme 2, below: which consists in treating (2-hydroxy-5-nitrophenyl) methyltriphenylphosphonium bromide (compound described in Chem. Ber. 1986, 119, 2169), with an acid chloride of formula R 1 COCl in which R 1 is defined as in formula (I), the isomers 5 (R) and 5 (S) of the compounds of formula (I) are prepared by reaction of a compound of formula (IV)
• 4 (S) and 4 (R) isomers of 4-methoxymethyl-1,3-dioxolan-2-one respectively with the 4 (S) and 4 (R) isomers of 4-methoxymethyl-1,3-dioxolan-2-one.
• 4 (S) -methoxymethyl-1,3-dioxolan-2-one is a known compound, the preparation of which is described in patent EP-0 511 031.
• Example 1 3- [2- (3,3,3-trifluoropropyl) benzofuran-5-yl] - 5 (R) -methoxymethyloxazolidin-2-one
• Example 1 12.4 g of product are obtained.
• Example 1 16 g of product are obtained. Melting point: 164 ° C.
• the compounds of the invention are collated in the following table with their physical characteristics.
• the compounds of the invention have been the subject of pharmacological tests making it possible to determine their inhibitory power of monoamine oxidase A and of monoamine oxidase B.
• the reaction is
• the Ki (MAO-A) vary between 1.2 nM and values greater than 1000 nM and the Ki (MAO-B) between 22 nM and values greater than 1000 nM.
• Certain compounds of the invention are selective MAO-A inhibitors, the Ki (MAO-B) / Ki (MAO-A) ratio possibly being greater than 200.
• Ki (MAO-B) / Ki (MAO-A) ratio can be between 0.1 and 10.
• the invention can be used for the preparation of drugs which are selective MAO-A inhibitors or mixed inhibitors of MAO-A and MAO-B, these drugs finding their use in therapeutics in particular in the treatment of depressive states of any kind , psychoses
• senile depression hypobulia
• phobias in particular social phobias
• mood disorders cognitive deficits linked to age, dementia or cerebrovascular or traumatic accidents, in improving general cerebral performance
• neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease and all memory disorders, anxiety, panic attacks, in the treatment of dependence and withdrawal related to consumption of alcohol, tobacco and / or
• the compounds of the invention may be presented, in association with at least one excipient, in the form of pharmaceutical compositions formulated with a view, in particular, to oral, parenteral or rectal administration, for example in the form of tablets, dragees, capsules,
• the dose of active ingredient administered per day can vary between 1 and 100 mg / kg, in one or more doses.

Landscapes

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

Applications Claiming Priority (3)

Publications (1)

Family

ID=9484383

Family Applications (1)

Country Status (5)

Families Citing this family (4)

Family Cites Families (10)

• 1995
  • 1995-11-09 FR FR9513256A patent/FR2741071B1/fr not_active Expired - Fee Related
• 1996
  • 1996-11-05 EP EP96937391A patent/EP0859775A1/fr not_active Withdrawn
  • 1996-11-05 WO PCT/FR1996/001731 patent/WO1997017346A1/fr not_active Application Discontinuation
  • 1996-11-05 US US09/066,365 patent/US6143772A/en not_active Expired - Fee Related
  • 1996-11-05 JP JP9517918A patent/JP2000500126A/ja active Pending

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events