EP2408778A1 - Derives de n-[(6-aza-bicyclo[3.2.1]oct-5-yl)-aryl-methyl]-heterobenzamide, leur preparation et leur application en therapeutique - Google Patents

Derives de n-[(6-aza-bicyclo[3.2.1]oct-5-yl)-aryl-methyl]-heterobenzamide, leur preparation et leur application en therapeutique

Info

Publication number
EP2408778A1
EP2408778A1 EP10715933A EP10715933A EP2408778A1 EP 2408778 A1 EP2408778 A1 EP 2408778A1 EP 10715933 A EP10715933 A EP 10715933A EP 10715933 A EP10715933 A EP 10715933A EP 2408778 A1 EP2408778 A1 EP 2408778A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
compound
phenyl
treatment
methyl
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Withdrawn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
EP10715933A
Other languages
German (de)
English (en)
French (fr)
Inventor
Geneviève ESTENNE-BOUHTOU
Florence Medaisko
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 SA
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
Application filed by Sanofi SA filed Critical Sanofi SA
Publication of EP2408778A1 publication Critical patent/EP2408778A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
    • 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
    • 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
    • A61P25/18—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

Definitions

  • dC 6 alkyl group represents a carbon chain of 1 to 6 carbon atoms, linear or branched, for example methyl, ethyl, propyl, isopropyl, butyl, te / f-butyl, pentyl, hexyl; alkenyl, a linear or branched, mono- or poly-unsaturated aliphatic group, for example comprising one or two ethylenic unsaturations, -alkoxy, a -O-alkyl group; hydroxy, -OH, alkyl-thio, alkyl-substituted sulfur; halogen atom, fluorine, chlorine, bromine or iodine, haloalkyl, alkyl group of which one or more hydrogen atoms have been substituted by halogen.
  • the compounds of the invention exhibit particular activity as inhibitors of Glyti glycine transporters, including an improved activity and safety profile.
  • the chiral compounds of general formula (I) can be obtained by separation of the racemic compounds by high performance liquid chromatography (HPLC) on a chiral column, or by separation by chromatography on silica gel of the chiral diastereoisomers of the amine of formula general (IIa) then debenzylation, as described in Scheme 2.
  • HPLC high performance liquid chromatography
  • the efficacy of the compound is determined by the IC 5 O, concentration of the compound which reduces by 50% the specific capture of glycine, defined by the difference in radioactivity incorporated by the control batch and the batch which received the glycine at 10 mM.
  • the compounds of the invention, in this test, have an Cl 50 of the order of 0.1 to 10 ⁇ M.
  • the compounds according to the invention can therefore be used for the preparation of medicaments, in particular inhibitory drugs of the glycine glycine transporter.
  • the tablets may be bare, sugar-coated, for example with sucrose, or coated with various polymers or other suitable materials. They can be designed to allow rapid, delayed or prolonged release of the active ingredient through polymer matrices or specific polymers used in the coating.
  • the capsules may be hard or soft, film-coated or not, so as to have a rapid, prolonged or delayed activity (for example for an enteric form).

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Neurology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Neurosurgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Addiction (AREA)
  • Hospice & Palliative Care (AREA)
  • Anesthesiology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
EP10715933A 2009-03-16 2010-03-15 Derives de n-[(6-aza-bicyclo[3.2.1]oct-5-yl)-aryl-methyl]-heterobenzamide, leur preparation et leur application en therapeutique Withdrawn EP2408778A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0901220A FR2943059A1 (fr) 2009-03-16 2009-03-16 Derives de n-°6-aza-bicyclo°3.2.1!oct-5-yl)-aryl-methyl!- heterobenzamide,leur preparation et leur application en therapeutique
PCT/FR2010/050448 WO2010106270A1 (fr) 2009-03-16 2010-03-15 Derives de n-[(6-aza-bicyclo[3.2.1]oct-5-yl)-aryl-methyl]-heterobenzamide, leur preparation et leur application en therapeutique

Publications (1)

Publication Number Publication Date
EP2408778A1 true EP2408778A1 (fr) 2012-01-25

Family

ID=40720092

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10715933A Withdrawn EP2408778A1 (fr) 2009-03-16 2010-03-15 Derives de n-[(6-aza-bicyclo[3.2.1]oct-5-yl)-aryl-methyl]-heterobenzamide, leur preparation et leur application en therapeutique

Country Status (17)

Country Link
US (1) US20120029027A1 (es)
EP (1) EP2408778A1 (es)
JP (1) JP2012520346A (es)
KR (1) KR20120013325A (es)
CN (1) CN102356084A (es)
AR (1) AR075838A1 (es)
AU (1) AU2010224721A1 (es)
BR (1) BRPI1009497A2 (es)
CA (1) CA2755528A1 (es)
FR (1) FR2943059A1 (es)
IL (1) IL215103A0 (es)
MX (1) MX2011009746A (es)
RU (1) RU2011141760A (es)
SG (1) SG174432A1 (es)
TW (1) TW201100431A (es)
UY (1) UY32496A (es)
WO (1) WO2010106270A1 (es)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2545964A1 (en) 2011-07-13 2013-01-16 Phenex Pharmaceuticals AG Novel FXR (NR1H4) binding and activity modulating compounds
ES2921432T3 (es) 2016-06-13 2022-08-25 Gilead Sciences Inc Derivados de azetidina como moduladores de FXR (NR1H4)
CA2968836A1 (en) 2016-06-13 2017-12-13 Gilead Sciences, Inc. Fxr (nr1h4) modulating compounds
ES2927019T3 (es) 2017-03-28 2022-11-02 Gilead Sciences Inc Combinaciones terapéuticas para el tratamiento de enfermedades hepáticas
DK3911647T3 (da) 2019-01-15 2024-02-26 Gilead Sciences Inc Isoxazol-forbindelse som FXR-agonist og farmaceutiske sammensætninger, der omfatter en sådan
CN113439078B (zh) 2019-02-19 2024-04-23 吉利德科学公司 Fxr激动剂的固体形式

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2861076B1 (fr) * 2003-10-17 2006-01-06 Sanofi Synthelabo Derives de n-heterocyclymethylbenzamide, leur preparation et leur application en therapeutique
TW200911808A (en) * 2007-07-23 2009-03-16 Astrazeneca Ab Novel compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2010106270A1 *

Also Published As

Publication number Publication date
BRPI1009497A2 (pt) 2018-03-13
FR2943059A1 (fr) 2010-09-17
CA2755528A1 (fr) 2010-09-23
JP2012520346A (ja) 2012-09-06
TW201100431A (en) 2011-01-01
AU2010224721A1 (en) 2011-10-06
UY32496A (es) 2010-10-29
SG174432A1 (en) 2011-10-28
US20120029027A1 (en) 2012-02-02
MX2011009746A (es) 2011-09-29
AR075838A1 (es) 2011-04-27
RU2011141760A (ru) 2013-04-27
WO2010106270A1 (fr) 2010-09-23
KR20120013325A (ko) 2012-02-14
IL215103A0 (en) 2011-12-29
CN102356084A (zh) 2012-02-15

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