US20070191359A1 - 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof - Google Patents

3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof Download PDF

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Publication number
US20070191359A1
US20070191359A1 US11/682,991 US68299107A US2007191359A1 US 20070191359 A1 US20070191359 A1 US 20070191359A1 US 68299107 A US68299107 A US 68299107A US 2007191359 A1 US2007191359 A1 US 2007191359A1
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Prior art keywords
conditions
compound
formula
preparation
patient
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US11/682,991
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English (en)
Inventor
Denis BRASSEUR
Claudine Serradeil-Le Gal
Gareth SHACKLETON
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Sanofi Aventis France
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Sanofi Aventis France
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Assigned to SANOFI-AVENTIS reassignment SANOFI-AVENTIS ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SHACKLETON, GARETH, SERRADEIL-LE GAL, CLAUDINE, BRASSEUR, DENIS
Publication of US20070191359A1 publication Critical patent/US20070191359A1/en
Priority to US12/504,260 priority Critical patent/US7910584B2/en
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/96—Spiro-condensed ring systems
    • 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
    • A61P1/08—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
    • A61P1/16—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
    • 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
    • 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
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/12—Ophthalmic agents for cataracts
    • 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
    • A61P27/16—Otologicals
    • 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
    • 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
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • 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
    • A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
    • 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
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to 3-spiroindolin-2-one derivatives, to the process for preparing them and to the therapeutic use thereof.
  • a subject of the present invention is compounds of formula (I): in the base, hydrate or solvate state, in the form of cis/trans isomers or of mixtures thereof.
  • the compounds of formula (I) contain one or more rings. They can therefore exist in the form of cis/trans isomers. These isomers and mixtures thereof are part of the invention.
  • the compounds of formula (I) can also exist in hydrate and/or solvate form, i.e. in the form of an association or of a combination with one or more molecules of water or with a solvent. Such hydrates and solvates are also part of the invention.
  • the compounds of the invention can be prepared according to scheme 1 which follows.
  • the compound of formula (V) is obtained by means of a step consisting of displacement of the tosylate group present in the compound of formula (VI), by an ethanolamine group, in the presence of a protic solvent such as ethanol or methanol.
  • a protic solvent such as ethanol or methanol.
  • the compound of formula (V) is subsequently converted to the compound of formula (IV) by means of a reaction consisting of acylation of the amine function with 2-bromoacetyl bromide or bromoacetyl chloride, in the presence of triethylamine and of an aprotic solvent such as dichloromethane (CH 2 Cl 2 ) or tetrahydrofuran (THF).
  • the compound of formula (IV) is then converted to the compound of formula (III) by means of a cyclization reaction in a basic medium, in the presence of a polar aprotic solvent such as THF, dimethyl-formamide or dimethyl sulfoxide.
  • the compound of formula (III) thus obtained is added to the compound of formula (II), in a basic medium and in the presence of benzyltriethylammonium chloride and in an aprotic solvent such as CH 2 Cl 2 or THF, so as to obtain the compound of formula (I).
  • aprotic solvent such as CH 2 Cl 2 or THF
  • the chromatography/mass spectrometry procedures were carried out on a Micromass® “TOF” (time of flight) mass spectrometer, model LCT.
  • the melting points were measured on a Büchi melting point B-545 device.
  • the mixture is subsequently washed with water and the aqueous phase is extracted several times with dichloromethane.
  • the organic phases are combined, subsequently dried over magnesium sulfate, filtered, and concentrated.
  • the crude product (8.26 g) is purified on silica gel (320 g; 40-63 ⁇ m particles; the eluent used is a gradient: pure CH 2 Cl 2 to a 95/5 CH 2 Cl 2 /methanol mixture).
  • the fractions containing the desired derivative are combined and concentrated under vacuum.
  • the crude product (1.73 g) is purified on silica gel (110 g; 40-63 ⁇ m particles; the eluent used is a gradient: pure CH 2 Cl 2 to a 96/4 CH 2 Cl 2 /methanol mixture) .
  • the fractions containing the desired derivative are combined and concentrated under vacuum.
  • 13 C NMR (150 MHz in DMSO D 6 ): 177.5; 166.4; 165.2; 157.1; 156.3; 143.6; 134.9; 131.4; 131.3; 127.1; 119.7; 114.5; 113.8; 112.4; 110.4; 79.5; 75.5; 67.8; 65.5; 63.9; 63.8; 56.7; 51.7; 47.7; 45.4; 31.4; 28.8; 26.4; 15.1.
  • the compounds according to the invention were subjected to pharmacological assays which show their advantage as active substances in therapy.
  • the affinity of the compounds of the invention for vasopressin V 2 receptors was determined in an in vitro binding assay according to the technique described below.
  • the affinity of the compounds of the invention for vasopressin V 2 receptors was measured in in vitro binding assays, as described in J. Pharmacol. Exp. Ther. , (2002), 300, pp. 1122-1130.
  • Plasma membranes (approximately 20 ⁇ g/ml) originating from tissues or the CHO cell line expressing recombinant human vasopressin V 2 receptors are incubated for 45 minutes at 25° C. in 200 ⁇ l of TRIS-HCl buffer (50 mM; pH 8.2) containing 2 mM of MgCl 2 , 1 mM of EDTA, 0.1% of BSA, 1 mg/ml of bacitracin and 3.5 nM of [H 3 ]-AVP. The reaction is stopped by filtration and washing over GF/B filters. The nonspecific binding is determined in the presence of 1 ⁇ M of AVP.
  • the compounds of the invention dissolved beforehand at the concentration of 10 ⁇ 2 M in DMSO, are tested in a dilution range.
  • IC 50 concentration of product that inhibits 50% of the specific binding
  • IC 50 values are generally less than 10 ⁇ 8 M.
  • the compound obtained according to the previous example of the present invention has an IC 50 of approximately 7.3 ⁇ 10 ⁇ 9 M.
  • the compounds according to the invention can be used for the preparation of medicaments, in particular V 2 receptor antagonist medicaments.
  • a subject of the invention is medicaments which comprise at least one compound of formula (I).
  • vasopressin V 2 receptor antagonists exhibit aquaretic properties in animals and humans ( Cardiovascular Drug Review , (2001), 3: pp. 201-214).
  • the compounds according to the invention have a large range of therapeutic indications and can advantageously replace conventional diuretics in all pathologies where they are recommended in humans and in animals.
  • the compounds according to the invention may be of use in particular in the treatment and/or the prevention of central and peripheral nervous system conditions, cardiovascular system conditions, conditions of the endocrine and hepatic system, of the renal sphere, of the gastric, intestinal and pulmonary sphere, in ophthalmology, and in sexual behavior disorders, in humans and in animals.
  • the compounds according to the invention can be used in the treatment and/or the prevention of various vasopressin-dependent conditions and also in vasopressin secretion dysfunctions such as the syndrome of inappropriate ADH secretion (or SIADH), cardiovascular conditions, such as hypertension, pulmonary hypertension, cardiac insufficiency, circulatory insufficiency, myocardial infarction, atherosclerosis or coronary vasospasm, in particular in smokers, unstable angina and percutaneous transluminal coronary angioplasty (or PTCA), cardiac ischemia, disturbances in hemostasis, in particular hemophilia, Von Willebrand syndrome; central nervous system conditions, migraine, cerebral vasospasm, cerebral hemorrhage, cerebral edema, depression, anxiety, bulimia, psychotic states, memory disorders, for example; rinopathies and kidney dysfunction such as edema, renal vasospasm, necrosis of the renal cortex, nephrotic syndrome, polycystic kidney disease
  • the compounds according to the invention can also be used in the treatment and/or the prevention of sexual behavior disorders, in conditions of being overweight or of excess weight and obesity by advantageously replacing the conventional diuretics already used for this indication.
  • the compounds according to the invention can be used for treating dysmenorrhea or premature labor.
  • the compounds according to the invention can also be used in the treatment of small cell lung cancers, hyponatremic encephalopathies, Raynaud's disease, pulmonary syndrome and glaucoma, and in the prevention of cataracts, in post-operative treatments, in particular after abdominal, cardiac or hemorrhagic surgery, and in treatments for disorders or diseases of the inner ear, such as Méley's disease, tinnitus, dizziness, hearing difficulties, in particular in the low-pitch range, or buzzing in the ears, hydrops, and in particular endolymphatic hydrops.
  • the present invention relates to pharmaceutical compositions comprising, as active ingredient, at least one compound according to the invention.
  • These pharmaceutical compositions contain an effective dose of at least one compound of formula (I) according to the invention, and also at least one pharmaceutically acceptable excipient.
  • Said excipients are chosen, according to the pharmaceutical form and the method of administration desired, from the usual excipients that are known to those skilled in the art.
  • compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal administration the active ingredient of formula (I) above, or its possible salt, solvate or hydrate, can be administered in unit administration form, as a mixture with conventional pharmaceutical excipients, to animals and to human beings for the prophylaxis or the treatment of the disorders or of the diseases above.
  • Suitable unit administration forms include oral administration forms, such as tablets, soft or hard gelatin capsules, powders, granules and oral solutions or suspensions, sublingual, buccal, intratracheal, intraocular or intranasal administration forms, forms for administration by inhalation, topical, transdermal, subcutaneous, intramuscular or intravenous administration forms, rectal administration forms, and implants.
  • oral administration forms such as tablets, soft or hard gelatin capsules, powders, granules and oral solutions or suspensions
  • sublingual, buccal, intratracheal intraocular or intranasal administration forms, forms for 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 unit administration form of a compound according to the invention in tablet form may comprise the following components: Compound according to 50.0 mg the example of the invention Mannitol 223.75 mg Sodium croscarmellose 6.0 mg Corn starch 15.0 mg Hydroxypropylmethylcellulose 2.25 mg Magnesium stearate 3.0 mg Said unit forms contain a dose so as to allow a daily administration of from 0.5 mg to 800 mg of active ingredient per individual, more particularly from 0.5 mg to 200 mg, according to the galenic form.
  • the dosage suitable for each patient is determined by the physician according to the method of administration and the weight and response of said patient.
  • the present invention also relates to a method of treating and/or preventing the pathologies indicated above, which comprises the administration, to a patient, of an effective dose of a compound according to the invention, or of a hydrate or solvate thereof.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Reproductive Health (AREA)
  • Neurology (AREA)
  • Otolaryngology (AREA)
  • Biomedical Technology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Neurosurgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Emergency Medicine (AREA)
  • Gynecology & Obstetrics (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
US11/682,991 2004-09-09 2007-03-07 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof Abandoned US20070191359A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/504,260 US7910584B2 (en) 2004-09-09 2009-07-16 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0451997 2004-09-09
FR0451997A FR2874920B1 (fr) 2004-09-09 2004-09-09 Derives de 3-spiro-indolin-2-one comme ligand des recepteurs de la vasopressine
PCT/FR2005/002219 WO2006030105A1 (fr) 2004-09-09 2005-09-07 Derives de 3-spiro-indolin-2-one comme ligand des recepteurs de la vasopressine

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/FR2005/002219 Continuation WO2006030105A1 (fr) 2004-09-09 2005-09-07 Derives de 3-spiro-indolin-2-one comme ligand des recepteurs de la vasopressine

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/504,260 Continuation US7910584B2 (en) 2004-09-09 2009-07-16 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof

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Publication Number Publication Date
US20070191359A1 true US20070191359A1 (en) 2007-08-16

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US11/682,991 Abandoned US20070191359A1 (en) 2004-09-09 2007-03-07 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof
US12/504,260 Expired - Fee Related US7910584B2 (en) 2004-09-09 2009-07-16 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof

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US12/504,260 Expired - Fee Related US7910584B2 (en) 2004-09-09 2009-07-16 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof

Country Status (6)

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US (2) US20070191359A1 (fr)
EP (1) EP1794123B1 (fr)
JP (1) JP2008512430A (fr)
AT (1) ATE537146T1 (fr)
FR (1) FR2874920B1 (fr)
WO (1) WO2006030105A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090275580A1 (en) * 2004-09-09 2009-11-05 Sanofi-Aventis 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8921376B2 (en) * 2005-05-20 2014-12-30 Vertex Pharmaceuticals Incorporated Pyrrolopyridines useful as inhibitors of protein kinase
FR2909668B1 (fr) * 2006-12-12 2009-01-23 Sanofi Aventis Sa Derives de 5-alkyloxy-indolin-2-one,leur preparation et leurs applications en therapeutique

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5994350A (en) * 1995-10-24 1999-11-30 Sanofi-Synthelabo 3-spiro-indolin-2-one derivatives as vasopressin and/or oxytocin receptor ligands

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2874921B1 (fr) * 2004-09-09 2006-10-20 Sanofi Aventis Sa Derives de 3-spiro-indolin-2-one, leur preparation et leur application en therapeutique

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5994350A (en) * 1995-10-24 1999-11-30 Sanofi-Synthelabo 3-spiro-indolin-2-one derivatives as vasopressin and/or oxytocin receptor ligands
US6046341A (en) * 1995-10-24 2000-04-04 Sanofi-Synthelabo 3-spiro-indolin-2-one derivatives

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090275580A1 (en) * 2004-09-09 2009-11-05 Sanofi-Aventis 3-spiroindolin-2-one derivatives, preparation and therapeutic use thereof

Also Published As

Publication number Publication date
EP1794123A1 (fr) 2007-06-13
JP2008512430A (ja) 2008-04-24
FR2874920A1 (fr) 2006-03-10
EP1794123B1 (fr) 2011-12-14
ATE537146T1 (de) 2011-12-15
WO2006030105A1 (fr) 2006-03-23
FR2874920B1 (fr) 2006-10-20
US20090275579A1 (en) 2009-11-05
US7910584B2 (en) 2011-03-22

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