EP1853595A1 - Derives de (1,5-diphenyl-1h-pyrazol-3-yl)oxadiazole, leur preparation et leur application en therapeutique - Google Patents

Derives de (1,5-diphenyl-1h-pyrazol-3-yl)oxadiazole, leur preparation et leur application en therapeutique

Info

Publication number
EP1853595A1
EP1853595A1 EP06709338A EP06709338A EP1853595A1 EP 1853595 A1 EP1853595 A1 EP 1853595A1 EP 06709338 A EP06709338 A EP 06709338A EP 06709338 A EP06709338 A EP 06709338A EP 1853595 A1 EP1853595 A1 EP 1853595A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
radical
compound
dichlorophenyl
formula
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Withdrawn
Application number
EP06709338A
Other languages
German (de)
English (en)
French (fr)
Inventor
Francis Barth
Christian Congy
Patrick Gueule
Murielle Rinaldi-Carmona
Didier Van Broeck
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi SA
Original Assignee
Sanofi Aventis France
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=35079215&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP1853595(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Sanofi Aventis France filed Critical Sanofi Aventis France
Publication of EP1853595A1 publication Critical patent/EP1853595A1/fr
Withdrawn legal-status Critical Current

Links

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
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • 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
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • 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
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/06—Antimigraine agents
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/32—Alcohol-abuse
    • 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
    • A61P25/34—Tobacco-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Definitions

  • the present invention relates to (1,5-diphenyl-1H-pyrazol-3-yl) oxadiazole derivatives, their preparation and their therapeutic application.
  • Diphenylpyrazole derivatives having an affinity for CB 1 receptors cannabinoids have been described in particular in the patents EP 0 576 357, EP 0 656 354 and US 5 624 941 and in the application WO 2005/000 820.
  • R 1 represents a heterocyclic radical chosen from:
  • a (C1-C7) alkyl unsubstituted or substituted with: a) one or more halogen atoms; b) a (C 1 -C 4) alkoxy, a trifluoromethoxy, or a phenoxy; c) an unsubstituted or mono-, di- or tri-substituted phenyl with substituents independently selected from a halogen atom, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical, a radical trifluoromethoxy d) an aromatic heterocyclic radical selected from thienyl, pyrrolyl, imidazolyl, furyl, pyrazolyl;
  • a non-aromatic carbocyclic radical C3-C12 or substituted or unsubstituted one or more times with a (C j-C4) alkyl; . unsubstituted or mono-, di- or trisubstituted phenyl with substituents independently selected from halogen, (C1-C4) alkyl, (C1-C4) alkoxy, trifluoromethyl or trifluoromethoxy;
  • a (C1-C7) alkyl unsubstituted or substituted with: a) one or more halogen atoms; b) a (C1-C4) alkoxy, trifluoromethoxy, or phenoxy; c) unsubstituted phenyl or mono-, di- or tri-substituted with substituents independently selected from a halogen atom, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical, a trifluoromethoxy radical; d) an aromatic heterocyclic radical selected from thienyl, pyrrolyl, imidazolyl, furyl, pyrazolyl; . a non-aromatic (C 3 -C 12) carbocyclic radical which is unsubstituted or substituted one or more times with a (C 1 -C 4) alkyl;
  • Ri c represents:
  • a (C1-C7) alkyl unsubstituted or substituted with: a) one or more halogen atoms; b) a (C1-C4) alkoxy, trifluoromethoxy, or phenoxy; c) unsubstituted or mono-, di- or tri-substituted phenyl with substituents independently selected from halogen, (C1-C4) alkyl, (C1-C4) alkoxy, trifluoromethyl, trifluoromethoxy; d) an aromatic heterocyclic radical selected from thienyl, pyrrolyl, imidazolyl, furyl, pyrazolyl; .
  • R 2 represents a (C 1 -C 5) alkyl or a cyano
  • R 3 represents an unsubstituted or mono-, di- or trisubstituted phenyl by substituents independently selected from a halogen atom, a
  • R 4 represents an unsubstituted or mono-, di- or trisubstituted phenyl with substituents independently selected from a halogen atom, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical, a trifluoromethoxy radical; or a group S (O) n AIk;
  • R5 and R ⁇ each independently represent a hydrogen atom or a (C1-C4) alkyl
  • R5 and R5 together with the nitrogen atom to which they are bonded constitute a heterocyclic radical chosen from azetidine, pyrrolidine, piperidine or morpholine;
  • R7 represents a hydrogen atom or a (C1-C3) alkyl
  • Rg represents a (C1-C4) alkyl
  • R 9 represents a (C 1 -C 4) alkyl
  • Rjo and Ri 1 each independently represent a hydrogen atom, a
  • R 2 represents a hydrogen atom, a (C 1 -C 7) alkyl, a (C 3 -C 7) cycloalkyl, a (C 3 -C 7) cycloalkylmethyl, a benzyl, a phenethyl;
  • R 13 represents a (C 1 -C 7) alkyl, a (C 3 -C 7) cycloalkyl, a (C 3 -C 7) cycloalkylmethyl, a benzyl, a phenethyl;
  • R 1 represents a (C 1 -C 7) alkyl, an unsubstituted phenyl or mono-, di- or trisubstituted by substituents independently selected from an atom halogen, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical or a trifluoromethoxy radical;
  • R 5 and R 1 are each independently hydrogen or (C 1 -C 4) alkyl; n represents 0, 1 or 2;
  • Alk represents a (C 1 -C 4) alkyl.
  • the compounds of formula (I) may comprise one or more asymmetric carbon atoms. They can therefore exist as enantiomers or diastereoisomers. These enantiomers, diastereoisomers and mixtures thereof, including racemic mixtures, form part of the invention.
  • the compounds of formula (I) may exist in the form of hydrates or solvates, namely in the form of associations or combinations with one or more molecules of water or with a solvent. Such hydrates and solvates are also part of the invention.
  • halogen atom is meant a bromine, chlorine, fluorine or iodine atom.
  • (C 1 -C 3) alkyl or (C 1 -C 4) alkyl, (C 1 -C 5) alkyl or (C 1 -C 7) alkyl it is meant a linear or branched alkyl radical of one to three carbon atoms or respectively of one with four carbon atoms, from one to five carbon atoms or from one to seven carbon atoms, such as the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyh, tert-butyl, pentyl and isopentyl radicals, hexyl, isohexyl, heptyl.
  • alkoxy is meant a linear or branched alkoxy radical of one to four carbon atoms such as the methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy radical.
  • cycloalkyl is meant a cyclic alkyl group of 3 to 7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl.
  • C3-C12 non-aromatic carbocyclic radicals include mono or polycyclic radicals, fused, bridged or spiranic.
  • Monocyclic radicals include cycloalkyls for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl.
  • the fused, bridged or spiro di- or tricyclic radicals include, for example, norbornyl, bornyl, isobornyl, noradamantyl, adamantyl, spiro [5.5] undecyl, bicyclo [2.2.1] heptyl, bicyclo [3.2.1] octyl radicals; bicyclo [3.1.1] heptyl.
  • R 1 represents a radical
  • R 21 , R 2, R 3, and R 4 are as defined for compounds of formula (I); compounds of formula (IB) in which R 1 represents a radical:
  • a non-aromatic (C 3 -C 12) carbocyclic radical which is unsubstituted or substituted one or more times with a (C 1 -C 4) alkyl; 0. unsubstituted or mono-, di- or trisubstituted phenyl with substituents independently selected from halogen, (C1-C4) alkyl, (C1-C4) alkoxy, trifluoromethyl or trifluoromethoxy; . a group -NR5R5; .
  • R2 is (C1-C5) alkyl or cyano
  • R 3 represents an unsubstituted or mono-, di- or trisubstituted phenyl by substituents independently selected from a halogen atom, a (C 1 -C 6 ) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical, a trifluoromethoxy radical or a group S (O) n Alk;
  • R4 represents unsubstituted or mono-, di- or tri-substituted phenyl by substituents independently selected from halogen, (C1-C4) alkyl, (C1-C4) alkoxy, trifluoromethyl, radical; trifluoromethoxy or a group S (O) n AIk;
  • R5 and R5 each independently represent a hydrogen atom or a (C 0 -C 4) alkyl
  • R5 and Rg together with the nitrogen atom to which they are bonded constitute a heterocyclic radical chosen from azetidine, pyrrolidine, piperidine or morpholine;
  • R7 represents a hydrogen atom or a (C 1 -C 3) alkyl;
  • R6 is (C1-C4) alkyl;
  • n O 5 1 or 2;
  • - Alk represents a (C1-C4) alkyl; in the basic state and in the state of hydrate or solvate.
  • a first group of 0 compounds consists of the compounds for which:
  • Ri represents a heterocyclic radical chosen from:
  • - R.2 represents a methyl, an ethyl, a cyano
  • R3 represents a 4-bromophenyl, a 4-chlorophenyl
  • R 4 represents a 2-chlorophenyl, a 2,4-dichlorophenyl; as well as their hydrates or their solvates.
  • tert-butylaminocarbonyl diethylaminocarbonyl, benzylamino carbonyl, piperid-1-ylcarbonyl; . mercapto, isopropylthio, isobutylthio, (1-ethylpropyl) thio, (cyclopropylmethyl) thio, benzylthio, 2-phenylethylthio;
  • R2 represents a methyl, an ethyl, a cyano
  • R3 represents a 4-bromophenyl, a 4-chloro ⁇ henyl
  • R 4 represents a 2-chlorophenyl, a 2,4-dichlorophenyl; as well as their hydrates or their solvates.
  • Another group of compounds consists of the compounds for which:
  • R3 represents a 4-chloro ⁇ henyl
  • R4 represents 2,4-dichlorophenyl
  • R3 represents a 4-chlorophenyl
  • R4 represents 2,4-dichlorophenyl; as well as their hydrates or their solvates.
  • R2 represents a methyl, an ethyl or a cyano
  • R3 represents a 4-bromophenyl or a 4-chlorophenyl
  • R 4 represents a 2-chlorophenyl or a 2,4-dichlorophenyl; as well as their hydrates or their solvates.
  • compounds of formula (I) that are subjects of the invention, mention may be made especially of the following compounds:
  • a protective group Pg is understood to mean a group that makes it possible, on the one hand, to protect a reactive function such as a hydroxyl or an amine during a synthesis and, on the other hand, to regenerate the intact reactive function. at the end of synthesis. Examples of protecting groups and methods of protection and deprotection are given in "Protective Group in Organic Synthesis", Green et al., 2nd Edition (John Wiley & Sons, Inc., New York), 1991.
  • leaving group is meant, in what follows, a group that can be easily cleaved from a molecule by breaking a heterolytic bond, with departure from an electronic pair. This group can thus be easily replaced by another group during a substitution reaction, for example.
  • Such leaving groups are, for example, halogens or an activated hydroxy group such as methanesulfonate, benzenesulfonate, p-toluenesulfonate, triflate, acetate, etc. Examples of starting groups and references for their preparation are given in Advances in
  • the compounds of formula (I) can be prepared according to the following methods.
  • the compounds of formula (I) in which R 1 can be prepared by a process which is characterized in that:
  • R 1 a , R 2, R 3 and R 4 are as defined for a compound of formula (I).
  • the cyclization reaction is generally carried out in the presence of a catalytic amount of an acid such as toluene-4-sulphonic acid, in a solvent such as toluene, at a temperature between room temperature and room temperature. reflux temperature of the solvent and removing water formed by azeotropy.
  • an acid such as toluene-4-sulphonic acid
  • the cyclization is carried out by reaction of the compound of formula (II) with toluene-4-sulphonyl chloride, in the presence of a base such as triethylamine, in a solvent such as dichloromethane and at a temperature of temperature between room temperature and the reflux temperature of the solvent.
  • the cyclization is carried out in the presence of phosphorus oxychloride according to the method described in J. Org. Chem. USSR, 1989, 25 (5), 935-940.
  • R a -NH 2 by reacting a compound of formula:
  • R2, R3 and R4 are as defined for a compound of formula (I), with cyanogen bromide in a solvent such as ethanol, at a temperature between room temperature and the reflux temperature of the solvent, monitoring • "• a hydrolysis in basic medium.
  • R5 and R5 are as defined for a compound of formula (I) and HaI represents a halogen atom, in the presence of a base such as triethylamine, in a solvent such as dichloromethane, at a temperature of between the ambient temperature and the reflux temperature of the solvent.
  • the reaction is carried out in the presence of a coupling agent used in peptide chemistry such as 1,3-dicyclohexylcarbodiimide or benzotriazol-1-yloxytris hexafluorophosphate ( dimethylamino) phosphonium or benzotriazol-1-yloxytris (pyrrolidino) phosphonium hexafluorophosphate or 2- (lY-benzotriazol) tetrafluoroborate yl) -l, l 5 3,3-tetramethyl Ur0 nium 5 in the presence of a base such as triethylamine, N, N-diisopropylethyl amine or 4-dimethylaminopyridine, in a solvent such as dichloromethane, dichloroethane, NN-dimethylformamide or tetrahydrofuran at a temperature between -10 ° C and the reflux temperature of the
  • the acid chloride As the functional derivative of the acid (V), it is possible to use the acid chloride, the anhydride, a mixed anhydride, a C 1 -C 4 alkyl ester in which the alkyl is straight or branched, an activated ester, for example the p-nitrophenyl ester.
  • N-methylmorpholine or pyridine N-methylmorpholine or pyridine.
  • R 1 according to a process which is characterized in that:
  • R1] 3 , R2, R3 and R4 are as defined for a compound of formula (I).
  • the cyclization reaction is generally carried out in a solvent such as n-butanol and at a temperature between room temperature and the reflux temperature of the solvent.
  • a base such as sodium hydride
  • the cyclization reaction is generally carried out in a solvent such as n-butanol at a temperature between room temperature and the reflux temperature of the solvent.
  • the compounds of formula (I) thus obtained may be subsequently separated from the reaction medium Q and purified according to conventional methods, for example by crystallization or chromatography.
  • R2, R3 and R4 are as defined for a compound of formula (I) 5 with an acid o ⁇ a functional derivative of this acid of formula:
  • the compounds of formula (III) are prepared from compounds of formula: wherein R2, R3 and R4 are as defined for a compound of formula (I) and Z is hydroxy or (C1-C2) alkoxy.
  • the compounds of formula (IV) are commercially available or described in the literature or can be prepared according to methods described therein or its t known to those skilled in the art such as reaction of phosgene with the corresponding amine.
  • the compounds of formula (VII) are known and are prepared according to known methods such as those described in EP 0 656 354, EP 0 576 357, WO 00/46209 and WO 2005/000820.
  • R 1 is as defined for a compound of formula (I), under the operating conditions as defined above for the reaction of a compound of formula (V).
  • the compounds of formula (XII) are prepared by reaction of a compound of formula:
  • R2, R3, and R4 are as defined for a compound of formula (I), with 0 an acid or a functional derivative of this acid of formula:
  • HOOC-R 10 in which R 1 c is as defined for a compound of formula (I), under the operating conditions as defined above for the reaction of a compound of formula (V).
  • the compounds of formula (XIH) are known or are prepared according to known methods such as the reaction of hydroxylamine with a compound of formula
  • the compounds of formula (XIV) are prepared by reacting hydroxylamine with a compound of formula:
  • R2, R3, and R4 are as defined for a compound of formula (I).
  • the compounds of formula (XVH) are prepared according to the processes described in EP 0 576 357.
  • the invention according to another of its aspects, also relates to certain novel compounds of formula ( ⁇ ), (XI), and XS). These compounds are useful as synthesis intermediates for the compounds of formula (I).
  • - R ⁇ a represents:. a (C 1 -C 7) alkyl unsubstituted or substituted with: a) one or more halogen atoms; b) a (C1-C4) alkoxy or phenoxy; c) an unsubstituted or mono-, di- or tri-substituted phenyl with substituents independently chosen from a halogen atom, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical or a trifluoromethoxy radical; ; d) an aromatic heterocyclic radical selected from thienyl, pyrrolyl, imidazolyl, furyl, pyrazolyl;
  • a non-aromatic carbocyclic radical (C3-C12) unsubstituted or substituted one or more times by (Ci-C4) alkyl; . unsubstituted or mono-, di- or trisubstituted phenyl with substituents independently selected from halogen, (C1-C4) alkyl, (C1-C4) alkoxy, trifluoromethyl or trifluoromethoxy; . a group -NR5R6; . a group -COOR9; R2 represents a (C1-C5) alkyl, a cyano;
  • R3 represents a phenyl which is unsubstituted or mono-, di- or trisubstituted by substituents independently selected from a halogen atom, a (C C4) alkyl, (C j-C4) alkoxy, a trifluoromethyl radical, a radical trifluoromethoxy or a group S (O) n AIk;
  • R 4 represents an unsubstituted or mono-, di- or trisubstituted phenyl by substituents independently selected from a halogen atom, a
  • R5 and R5 each independently represent a hydrogen atom or a (C -C 4) alkyl; or else R5 and Rg together with the nitrogen atom to which they are bonded constitute a heterocyclic radical chosen from azetidine, pyrrolidine, piperidine or morpholine; .
  • Rg represents a (C 1 -C 4) alkyl; N is 0, 1 or 2;
  • Alk represents a (C 1 -C 4) alkyl.
  • R2 represents a methyl, an ethyl, a cyano
  • R3 represents a 4-bromophenyl, a 4-chlorophenyl
  • R4 is 2-chlorophenyl, 2,4-dichlorophenyl.
  • R2 represents a (C1-C5) alkyl or a cyano
  • J - R 3 is phenyl unsubstituted or mono-, di- or trisubstituted by substituents independently selected from a halogen atom, a (C C4) alkyl, (C1-C4) alkoxy, trifluoromethyl, trifluoromethoxy or S (O) n Alk;
  • R 4 represents an unsubstituted or mono-, di- or trisubstituted phenyl with substituents independently selected from a halogen atom, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical, a trifluoromethoxy radical; or a group S (O) n AIk;
  • R 1 and R 1 represent each independently a hydrogen atom or a
  • n 0, 1 or 2;
  • Alk represents a (C 1 -C 4) alkyl.
  • R3 represents a 4-chlorophenyl
  • a (C1-C7) alkyl unsubstituted or substituted with: a) one or more halogen atoms; b) a (C 1 -C 4) alkoxy or phenoxy; c) unsubstituted phenyl or mono-, di- or tri-substituted with substituents independently selected from a halogen atom, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical, a trifluoromethoxy radical; d) an aromatic heterocyclic radical selected from thienyl, pyrrolyl, imidazolyl, furyl, pyrazolyl; . a non-aromatic (C 3 -C 12) carbocyclic radical which is unsubstituted or substituted one or more times with a (C 1 -C 4) alkyl;
  • R2 represents a (C1-C5) alkyl or a cyano
  • R 3 represents an unsubstituted or mono-, di- or trisubstituted phenyl by substituents independently selected from a halogen atom, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical, a trifluoromethoxy radical or a group S (O) n Alk;
  • R 4 represents an unsubstituted or mono-, di- or tri-substituted phenyl with substituents independently chosen from a halogen atom, a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy, a trifluoromethyl radical or a radical; trifluoromethoxy or a group S (O) n AIk;
  • R 1 and R 1 are each independently hydrogen or (C 1 -C 4 ) alkyl
  • n 0, 1 or 2;
  • AlIc represents a (C 1 -C 4) alkyl.
  • R3 represents a 4-chlorophenyl
  • R4 represents a 2,4-dichlorophenyl.
  • DPEA diisopropylethylamine
  • TFA trifluoroacetic acid 2N hydrochloric ether: 2N solution of hydrochloric acid in diethyl ether
  • Silica H silica gel 60 H marketed by Merck (DARMSTAD)
  • Buffer solution pH 2: solution of 16.66 g of KHSO4 and 32.32 g of K2SO4 in 1 liter of water.
  • Nuclear magnetic resonance spectra are recorded at 200 MHz in DMSO-dg.
  • s singlet
  • d doublet
  • t triplet
  • qd quadruplet
  • qt quintuplet
  • m massive
  • mt multiplet
  • se widened singlet
  • dd doublet of doublet
  • spt sepruplet.
  • the compounds according to the invention are analyzed by LC / UV / MS coupling (liquid chromatography / UV detection / mass spectrometry).
  • the molecular peak (MH) and the retention time (tr) are measured in minutes.
  • the device marketed by Agilent, consists of an HP 1100 chromatograph equipped with an Agilent diode array detector and a Quad Quadrupole MSD Quad mass spectrometer.
  • a symmetry C 18 column of 2.1 ⁇ 50 mm, 3.5 ⁇ m, is used at 30 ° C., flow rate 0.4 ml / minute.
  • the eluent is composed as follows:
  • solvent A 0.005% trifluoroacetic acid (TFA) in water at pH 3.15;
  • solvent B 0.005% of TFA in acetonitrile.
  • ESI electrospray
  • This compound is prepared according to the procedures described in WO 2005/000.
  • This compound is prepared according to the procedures described in WO 2005/000.
  • a mixture of 1.82 g of tert-butyl hydrazine carboxylate and 2.4 ml of triethylamine in 50 ml of DCM is cooled to 0 ° C., a solution of 5.24 g of the compound obtained in step A is added. in 50 ml of DCM and left stirring, allowing the temperature to rise to RT.
  • step B To a solution of 12.7 g of the compound obtained in step B in 200 ml of MeOH is added 40 ml of 2N hydrochloric ether and then heated at 40 ° C for 3 hours. The reaction mixture is concentrated under vacuum, the residue is extracted with ether, the organic phase is washed twice with 10% NaHCO 3 solution, the organic phase is dried over MgSO 4 and the solvent is evaporated under vacuum. 8.3 g of the expected compound are obtained after crystallization from the ether / pentane mixture.
  • reaction mixture is extracted with DCM, the organic phase washed with water, dried over MgSO 4 e * evaporate the solvent in vacuo. 3.7 g of the expected compound are obtained.
  • a mixture of 10 g of the compound of the compound is heated at 60 ° C. for 1 hour.
  • EXAMPLE 19 Compound No. 62 2- (benzylsulfinyl) -5- [5- (4-bromophenyl) -l- (2,4-dichlorophenyl) -4-ethyl-lH "- pyrazol-3-yl] -l, 3,4-oxadiazole.
  • the compounds of formula (I) have a very good affinity in vitro (IC5Q ⁇
  • the toxicity of the compounds of formula (I) is compatible with their use as a medicament.
  • the subject of the invention is medicaments which comprise a compound of formula (I), or a solvate or a hydrate of the compound of formula (I).
  • the compounds according to the invention can be used in humans or animals, in the treatment or prevention of diseases involving cannabinoid receptors CBj.
  • the compounds of formula (I) are useful as psychotropic drugs, especially for the treatment of psychiatric disorders including anxiety, depression, mood disorders, insomnia, delusional disorders , obsessive-compulsive disorder, psychosis in general, schizophrenia, attention deficit and hyperactivity disorder (ADHD) in hyperkinetic children (BDM), and the treatment of disorders related to the use of psychotropic substances, particularly in the case of substance abuse and / or substance dependence, including alcohol dependence and nicotine addiction.
  • psychiatric disorders including anxiety, depression, mood disorders, insomnia, delusional disorders , obsessive-compulsive disorder, psychosis in general, schizophrenia, attention deficit and hyperactivity disorder (ADHD) in hyperkinetic children (BDM), and the treatment of disorders related to the use of psychotropic substances, particularly in the case of substance abuse and / or substance dependence, including alcohol dependence and nicotine addiction.
  • the compounds of formula (I) according to the invention can be used as medicaments for the treatment of migraine, stress, psychosomatic diseases, panic attacks, epilepsy, movement disorders , especially dyskinesias or Parkinson's disease, tremors and dystonia.
  • the compounds of formula (I) according to the invention can also be used as medicaments in the treatment of memory disorders, cognitive disorders, in particular in the treatment of senile dementias, of Alzheimer's disease, as well as in the treatment of disturbances of attention or alertness.
  • the compounds of formula (I) may be useful as neuroprotective agents, in the treatment of ischemia, head trauma and the treatment of neurodegenerative diseases: including chorea, Huntington's chorea, Tourrette's syndrome.
  • the compounds of formula (I) according to the invention can be used as medicaments in the treatment of pain: neuropathic pain, acute peripheral pain, chronic pain of inflammatory origin.
  • the compounds of formula (I) according to the invention can be used as medicaments in the treatment of appetite disorders, cravings (for sugars, carbohydrates., Drugs, alcohol or any appetizing substance) and / or eating behaviors, in particular for the treatment of obesity or bulimia as well as for the treatment of type II diabetes or non-insulin-dependent diabetes and for the treatment of dyslipidemia, metabolic syndrome.
  • the compounds of formula (I) according to the invention are useful in the treatment of obesity and the risks associated with obesity, in particular cardiovascular risks.
  • the compounds of formula (I) according to the invention can be used as medicaments in the treatment of gastrointestinal disorders, diarrheal disorders, ulcers, vomiting, bladder and urinary disorders, endocrine, cardiovascular disorders, hypotension, hemorrhagic shock, septic shock, chronic cirrhosis of the liver, fatty liver, steatohepatitis, asthma, Raynaud's syndrome, glaucoma , disorders of fertility, premature termination of pregnancy, inflammatory phenomena, diseases of the immune system, in particular autoimmune and neuroinflammatory such as rheumatoid arthritis, reactive arthritis, diseases causing demyelination, multiple sclerosis in plaque, infectious and viral diseases such as encephalitis, stroke and as drugs for chemistry. anticancer therapy, for the treatment of Guillain-Barré syndrome and for the treatment of osteoporosis.
  • the compounds of formula (I) are particularly useful for the treatment of psychotic disorders, in particular schizophrenia, attention deficit and hyperactivity disorders (ADHD) in hyperkinetic children (BDM); for the treatment of appetite and obesity disorders; for the treatment of memory and cognitive deficits; for the treatment of alcohol dependence, nicotine addiction, ie for alcohol withdrawal and smoking cessation.
  • psychotic disorders in particular schizophrenia, attention deficit and hyperactivity disorders (ADHD) in hyperkinetic children (BDM); for the treatment of appetite and obesity disorders; for the treatment of memory and cognitive deficits; for the treatment of alcohol dependence, nicotine addiction, ie for alcohol withdrawal and smoking cessation.
  • the present invention relates to the use of a compound of formula (I), and their solvates or hydrates for the treatment of the disorders and diseases indicated above.
  • the present invention relates to pharmaceutical compositions comprising, as active principle, a compound according to the invention.
  • These pharmaceutical compositions contain an effective dose of at least one compound according to the invention, a solvate or hydrate of said compound, as well as at least one pharmaceutically acceptable excipient.
  • Said excipients are chosen according to the pharmaceutical form and the desired mode of administration, from the usual excipients which are known to those skilled in the art.
  • compositions according to the present invention may contain, besides a compound of formula (I), one (or more) other active ingredient useful in the treatment of the disorders and diseases indicated above.
  • an AT1 receptor antagonist of angiotensin II alone or in combination with a diuretic an AT1 receptor antagonist of angiotensin II alone or in combination with a diuretic
  • an inhibitor of the conversion enzyme alone or in combination with a diuretic or a calcium antagonist; a calcium antagonist;
  • beta-blocker alone or in combination with a diuretic or a calcium antagonist
  • an antihyperlipidemic agent or an antihypercholesterolemic agent an antihyperlipidemic agent or an antihypercholesterolemic agent
  • a nicotinic agonist another anti-obesity agent; a nicotinic agonist, a partial nicotinic agonist;
  • an antidepressant an antispychotic
  • an anticancer agent or an antiproliferative agent an anticancer agent or an antiproliferative agent
  • an opioid antagonist as well as: - an agent useful in the treatment of alcoholism or withdrawal symptoms;
  • angiotensin II AT1 receptor antagonist is meant a compound such as candesartan cilexitil, eprosartan, irbesartan, losartan potassium, olmesartan medoxomil, telmisartan, valsartan, each of these compounds may itself be associated with a diuretic such as rhydrochlorothiazide .
  • conversion enzyme inhibitor is meant a compound such as alacepril, benazepril, captopril, cilazapril, enalapril, enalaprilat, fosinopril, imidapril, lisinopril, moexipril, perindopril, quinapril, ramipril, spirapril, temocapril, trandolapril, zofenopril, each of these compounds may itself be associated with a diuretic such as rhydrochlorothiazide or rindapamide or a calcium antagonist such as amlodipine, diltiazem, felodipine or verapamil.
  • diuretic such as rhydrochlorothiazide or rindapamide
  • calcium antagonist such as amlodipine, diltiazem, felodipine or verapamil.
  • calcium antagonist is meant a compound such as amlodipine, aranidipine, benidipine, bepridil, cilnidipine, diltiazem, efonidipine hydrochloride ethanol, fasudil, felodipine, isradipine, lacidipine, lercanidipine hydrochloride, manidipine, mibefradil hydrochloride, nicardipine, nifedipine, nilvadipine, nimodipine, Nisoldipine, Nitrendipine, Terodiline, Verapamil.
  • beta-blocker is meant a compound such as acebutolol, alprenolol, amosulalol, arotinolol, atenolol, befunolol, betaxolol, bevololol, bisoprolol, bopindolol, bucumolol, bufetolol, bunitrolol, butofilolol, carazolol, cardolol, carvedilol, cloranolol, epanolol, esmolol.
  • antihyperlipidemic or antihypercholesterolaemic is meant a compound selected from febrites such as alufibrate, beclobrate, bezafibrate, ciprofibrate, clinofîbrate, clofibrate, etofibrate, fenofibrate; statins (HMG-CoA reductase inhibitors), such as atorvastatin, fluvastatin sodium, lovastatin, pravastatin, rosuvastatin, simvastatin, or a compound such as acipimox, alummum nicotinate, azacosterol, cholestyramine, dextrothyroxine, meglutol, niceritrol, nicoclonate, nicotinic acid , beta-sitosterol, tiadenol.
  • statins HMG-CoA reductase inhibitors
  • antidiabetic means a compound belonging to one of the following classes: sulfonylureas, biguanidines, alpha glucosidase inhibitors, thiazolidinedione, methaglinides, such as acarbose, acetohexamide, carbutamide, chlorpropamide, glibenclamide, glibornuride, gliclazide , glimepiride, glipizide, gliquidone, glisoxepide, glybuzole, glymidine, metahexamide, metformin, miglitol, nateglinide, pioglitazone, repaglinide, rosiglitazone, tolazamide, tolbutamide, troglitazone, voglibose, as well as insulin and insulin analogues.
  • sulfonylureas biguanidines
  • alpha glucosidase inhibitors such
  • anti-obesity agent a compound such as amfepramone, benfluorex, benzphetamine, indanorex, mazindole, mefenorex, methamphetamine, D-norpseudoephedrine, sibutramine, a lipase inhibitor (orlistat cetilistat), a PPAR agonist, a dopamine agonist, a leptin receptor agonist, a serotonin receptor inhibitor, a beta-3 agonist, a CCK-A agonist, an NPY inhibitor, an MC4 receptor agonist, a bombesin agonist.
  • opioid antagonist is meant a compound such as naltrexone, naloxone or nalmefene.
  • agent useful in the treatment of alcoholism as well as withdrawal symptoms is meant acamprosate, benzodiazepines, beta-blockers, clonidine, carbamazepine.
  • beneficial agent for treating osteoporosis, is meant, for example, bisphosphonates such as etidronate, clodronate, tiludronate, risedronate.
  • the active ingredient of formula (I) above, or its salt, solvate or hydrate may be administered in unit dosage form, in admixture with conventional pharmaceutical excipients, to animals and humans for the prophylaxis or treatment of the above disorders or diseases.
  • Suitable unit dosage forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sublingual, oral, intratracheal, intraocular, intranasal forms of administration. by inhalation, topical, transdermal, subcutaneous, intramuscular or intravenous administration forms, rectal administration forms and implants.
  • the compounds according to the invention can be used in creams, gels, ointments or lotions.
  • a unitary form of administration of a compound according to the invention in tablet form may comprise the following components: Compound according to the invention 50.0 mg
  • the dose of active ingredient administered per day can reach 0.01 to 100 mg / kg, in one or more doses, preferably 0.02 to 50 mg / kg.
  • the dosage appropriate to each patient is determined by the physician according to the mode of administration, the weight and the response of said patient.
  • the present invention also relates to a method of treatment of the pathologies indicated above which comprises the administration to a patient of an effective dose of a compound according to the invention, or one of its pharmaceutically acceptable salts or hydrates or solvates.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Addiction (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Communicable Diseases (AREA)
  • Pulmonology (AREA)
  • Oncology (AREA)
  • Reproductive Health (AREA)
  • Ophthalmology & Optometry (AREA)
  • Vascular Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Obesity (AREA)
  • Virology (AREA)
EP06709338A 2005-02-21 2006-02-17 Derives de (1,5-diphenyl-1h-pyrazol-3-yl)oxadiazole, leur preparation et leur application en therapeutique Withdrawn EP1853595A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0501860A FR2882365B1 (fr) 2005-02-21 2005-02-21 Derives de 2-(1,5-diphenyl-1h-pyrazol-3-yl)-1,3,4-oxadiazole leur preparation et leur application en therapeutique
PCT/FR2006/000368 WO2006087480A1 (fr) 2005-02-21 2006-02-17 DERIVES DE (l,5-DIPHENYL-lH-PYRAZOL-3-YL)OXADIAZOLE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE

Publications (1)

Publication Number Publication Date
EP1853595A1 true EP1853595A1 (fr) 2007-11-14

Family

ID=35079215

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06709338A Withdrawn EP1853595A1 (fr) 2005-02-21 2006-02-17 Derives de (1,5-diphenyl-1h-pyrazol-3-yl)oxadiazole, leur preparation et leur application en therapeutique

Country Status (25)

Country Link
US (1) US7632852B2 (es)
EP (1) EP1853595A1 (es)
JP (1) JP4812778B2 (es)
KR (1) KR20070107053A (es)
CN (1) CN101119990A (es)
AR (1) AR055560A1 (es)
AU (1) AU2006215443A1 (es)
BR (1) BRPI0606845A2 (es)
CA (1) CA2597359A1 (es)
DO (1) DOP2006000045A (es)
EA (1) EA200701779A1 (es)
FR (1) FR2882365B1 (es)
GT (1) GT200600082A (es)
IL (1) IL185163A0 (es)
MA (1) MA29261B1 (es)
MX (1) MX2007009994A (es)
NO (1) NO20074763L (es)
NZ (1) NZ560790A (es)
PA (1) PA8663901A1 (es)
PE (1) PE20061038A1 (es)
SV (1) SV2007002422A (es)
TW (1) TW200640916A (es)
UY (1) UY29388A1 (es)
WO (1) WO2006087480A1 (es)
ZA (1) ZA200706953B (es)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10361258A1 (de) * 2003-12-24 2005-07-28 Schwarz Pharma Ag Verwendung von substituierten 2-Aminotetralinen zur vorbeugenden Behandlung von Morbus Parkinson
WO2008017381A1 (de) 2006-08-08 2008-02-14 Sanofi-Aventis Arylaminoaryl-alkyl-substituierte imidazolidin-2,4-dione, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und ihre verwendung
US7875647B2 (en) 2006-09-29 2011-01-25 Green Cross Corporation Heteroaryl-pyrazole derivatives as cannabinoid CB1 receptor antagonists
CN101528740B (zh) * 2006-09-29 2012-09-19 株式会社绿十字 作为大麻素cb1受体拮抗剂的杂芳基-吡唑衍生物
US20080207704A1 (en) * 2007-02-27 2008-08-28 The Green Cross Corporation Heteroaryl-imidazole derivatives as cannabinoid cb1 receptor antagonists
US7705024B2 (en) 2007-04-12 2010-04-27 National Health Research Institutes Oxadiazole compounds
EP2025674A1 (de) 2007-08-15 2009-02-18 sanofi-aventis Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
WO2009078498A1 (en) * 2007-12-17 2009-06-25 Green Cross Corporation Biarylpyrazole 4-carboxamides as cannabinoid cb1 receptor ligands
TW201014822A (en) 2008-07-09 2010-04-16 Sanofi Aventis Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof
WO2010035915A1 (en) * 2008-09-25 2010-04-01 Green Cross Corporation Sulfur containing pyrazole-heterocycle derivatives as cannabinoid cb1 receptor antagonists
WO2010068601A1 (en) 2008-12-08 2010-06-17 Sanofi-Aventis A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof
SG178880A1 (en) 2009-08-26 2012-04-27 Sanofi Sa Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use
US8933024B2 (en) 2010-06-18 2015-01-13 Sanofi Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases
WO2012120054A1 (de) 2011-03-08 2012-09-13 Sanofi Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
WO2012120052A1 (de) 2011-03-08 2012-09-13 Sanofi Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung
US8828995B2 (en) 2011-03-08 2014-09-09 Sanofi Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
EP2683699B1 (de) 2011-03-08 2015-06-24 Sanofi Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
WO2012120056A1 (de) 2011-03-08 2012-09-13 Sanofi Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
CN109651350B (zh) * 2019-01-11 2022-05-24 贵州大学 一类杂环取代的1,3,4-噁(噻)二唑类化合物及其制备方法和用途
CN109942567B (zh) * 2019-04-30 2023-04-07 贵州大学 一种1,3,4-噁(噻)二唑基的咪唑类化合物及其制备方法和用途

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09124571A (ja) * 1995-11-01 1997-05-13 Japan Tobacco Inc アミド化合物及びその用途
FR2758723B1 (fr) * 1997-01-28 1999-04-23 Sanofi Sa Utilisation des antagonistes des recepteurs aux cannabinoides centraux pour la preparation de medicaments
US6825209B2 (en) * 2002-04-15 2004-11-30 Research Triangle Institute Compounds having unique CB1 receptor binding selectivity and methods for their production and use
CA2502511A1 (en) * 2002-10-18 2004-05-29 Pfizer Products Inc. Cannabinoid receptor ligands and uses thereof
CA2505945A1 (en) * 2002-12-02 2004-06-17 Fujisawa Pharmaceutical Co., Ltd. Pyrazole derivatives useful as cox-i inhibitors
FR2856683A1 (fr) * 2003-06-25 2004-12-31 Sanofi Synthelabo Derives de 4-cyanopyrazole-3-carboxamide, leur preparation et leur application en therapeutique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2006087480A1 *

Also Published As

Publication number Publication date
TW200640916A (en) 2006-12-01
JP2008530188A (ja) 2008-08-07
CA2597359A1 (fr) 2006-08-24
AU2006215443A1 (en) 2006-08-24
MX2007009994A (es) 2007-10-10
ZA200706953B (en) 2009-03-25
US7632852B2 (en) 2009-12-15
KR20070107053A (ko) 2007-11-06
UY29388A1 (es) 2006-10-02
JP4812778B2 (ja) 2011-11-09
FR2882365B1 (fr) 2007-09-07
MA29261B1 (fr) 2008-02-01
CN101119990A (zh) 2008-02-06
GT200600082A (es) 2006-10-19
NO20074763L (no) 2007-11-16
DOP2006000045A (es) 2006-11-15
AR055560A1 (es) 2007-08-22
FR2882365A1 (fr) 2006-08-25
NZ560790A (en) 2009-08-28
PA8663901A1 (es) 2006-12-07
IL185163A0 (en) 2007-12-03
EA200701779A1 (ru) 2008-02-28
BRPI0606845A2 (pt) 2009-07-21
US20080039510A1 (en) 2008-02-14
SV2007002422A (es) 2007-01-17
PE20061038A1 (es) 2006-11-24
WO2006087480A1 (fr) 2006-08-24

Similar Documents

Publication Publication Date Title
EP1853595A1 (fr) Derives de (1,5-diphenyl-1h-pyrazol-3-yl)oxadiazole, leur preparation et leur application en therapeutique
EP1853557A2 (fr) Derives de 1,5-diarylpyrrole, leur preparation et leur application en therapeutique
EP2094706B1 (fr) Derives de 2,5-dfflydro-3h-pyrazolo[4,3-c]pyridazin-3-one substitues, leur preparation et leur utilisation comme ligands des recepteurs cb1 des cannabinoides
WO2006070106A1 (fr) DERIVES DE N- [ (4 , 5-DIPHENYL-3-ALKYL-2-THIENYL) METHYL] AMINE (AMIDE, SULFONAMIDE, CARBAMATE ET UREE) COMME ANTAGONISTS DES RECEPTEURS CBl DES
FR2864958A1 (fr) Derive de n-[(1,5-diphenyl-1h-pyrazol-3-yl)methyl] sulfonamide, leur preparation et leur application en therapeutique.
EP1899298B1 (fr) Derives de 4,5-diarylpyrrole, leur preparation et leur application en therapeutique
EP2094656B1 (fr) Derives de pyrrole, leur preparation et leur utilisation en therapeutique.
WO2006042955A1 (fr) Derives de pyridine, leur preparation, leur application en therapeutique
CA2576717A1 (fr) Derives de pyrrole, leur preparation et leur utilisation en therapeutique
EP1937672B1 (fr) Derives de n-[(4,5-diphenylpyrimidin-2-yl)methyl]amine, leur preparation et leur application en therapeutique
EP2108012A2 (fr) Derives de n-(4-cyano-l h-p yrazol-3 -yl)methylamine substitues, leur preparation et leur application en therapeutique
EP2283007A2 (fr) Dérivés de 1,5-diphénylepyrrole-3-carboxamide, leur preparation et leur utilisation comme antagonistes des récepteurs cb1 des cannabinoïdes
EP2283008B1 (fr) Derives de 4,5-diphenylepyrrole-2-ylcarboxamide, leur preparation et leur utilisation comme antagonistes des recepteurs cb1 des cannabinoides
EP2411383B1 (fr) Derives de 3-alcoxy-4,5-diarylthiophene-2-carboxamide, leur preparation et leur application en therapeutique

Legal Events

Date Code Title Description
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: 20070921

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA HR MK YU

17Q First examination report despatched

Effective date: 20090415

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SANOFI

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SANOFI

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SANOFI

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: 20120417