WO2004050627A1 - Derives d'amide quinoleique utilises comme agents contre des troubles du snc - Google Patents

Derives d'amide quinoleique utilises comme agents contre des troubles du snc Download PDF

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Publication number
WO2004050627A1
WO2004050627A1 PCT/EP2003/013796 EP0313796W WO2004050627A1 WO 2004050627 A1 WO2004050627 A1 WO 2004050627A1 EP 0313796 W EP0313796 W EP 0313796W WO 2004050627 A1 WO2004050627 A1 WO 2004050627A1
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WIPO (PCT)
Prior art keywords
compound
formula
disorders
pharmaceutically acceptable
solvate
Prior art date
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PCT/EP2003/013796
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English (en)
Inventor
Peter John Lovell
Halina Teresa Serafinowska
Paul William Smith
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Smithkline Beecham Corporation
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Publication date
Application filed by Smithkline Beecham Corporation filed Critical Smithkline Beecham Corporation
Priority to AU2003292196A priority Critical patent/AU2003292196A1/en
Publication of WO2004050627A1 publication Critical patent/WO2004050627A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/50—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4
    • C07D215/52—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4 with aryl radicals attached in position 2
    • 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

Definitions

  • the present invention relates to a novel quinoline derivative, processes for its preparation, pharmaceutical compositions containing it, and its use in medicine.
  • the mammalian peptide Neurokinin B belongs to the Tachykinin (TK) peptide family which also include Substance P (SP) and Neurokinin A (NKA).
  • TK Tachykinin
  • SP Substance P
  • NKB Neurokinin A
  • NK- receptor antagonists are known (Drapeau, 1990 Regul. Pept, 31, 125-135), and findings with peptidic NK 3 receptor agonists suggest that NKB, by activating the NK 3 receptor, has a key role in the modulation of neural input in airways, skin, spinal cord and nigro-striatal pathways (Myers and Undem, 1993, J.Phisiol., 470, 665-679; Counture et al., 1993, Regul. Peptides, 46, 426-429; Mccarson and Krause, 1994, J. Neurosci., 14 (2), 712-720; Arenas et al. 1991, J.NeuroscL, 11, 2332-8).
  • WO-A-95/32948 discloses certain selective, non- peptide NK 3 antagonists of formula (A) or salts or solvates thereof
  • X, R, Ar, and Ri to R 5 are as defined therein, which are of potential therapeutic utility in treating various disorders, including pulmonary disorders, skin disorders and itch, neurogenic inflammation and CNS disorders, and convulsive disorders, renal disorders, urinary incontinence, ocular inflammation, inflammatory pain, eating disorders, allergic rhinitis, neurodegenerative disorders, psoriasis, Huntington's disease and depression.
  • X may represent oxygen
  • Ar may represent an optionally substituted phenyl group
  • R may represent a linear or branched Ci-salkyl group
  • R-i may represent hydrogen
  • R 2 may represent hydrogen
  • R3 may represent hydrogen
  • R4 may represent amino
  • R5 may represent an optionally substituted aryl group.
  • a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof together with one or more pharmaceutically acceptable carrier(s), diluent(s) and/or excipient(s);
  • a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof for use in therapy is a pharmaceutically acceptable salt or solvate thereof for use in therapy
  • a method of treating a patient suffering from certain CNS or CNS-mediated disorders as hereinafter described comprising administering a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof.
  • the compound of formula (I) has S stereochemistry at the chiral centre, as depicted above.
  • the invention also extends to any tautomeric forms and mixtures thereof.
  • the compound of the present invention shows advantageous properties.
  • it possesses one or more of the following characteristics as compared to prior art compounds, including those compounds specifically disclosed in WO 95/32948: (i) it provides a higher in vivo brain concentration of pharmacologically active compound after appropriate dosing;
  • the term "pharmaceutically acceptable” means a compound which is suitable for pharmaceutical use.
  • the compound of formula (I) or salt or solvate thereof is preferably in pharmaceutically acceptable or substantially pure form.
  • pharmaceutically acceptable form is also meant, inter alia, of a pharmaceutically acceptable level of purity excluding normal pharmaceutical additives such as diluents and carriers, and including no material considered toxic at normal dosage levels.
  • a substantially pure form will generally contain at least 50% (excluding normal pharmaceutical additives), preferably 75%, more preferably 90% and still more preferably 95% of the compound of formula (I) or a salt or solvate thereof.
  • the compounds of formula (I) may be prepared in crystalline or non-crystalline form.
  • a preferred pharmaceutically acceptable form is a crystalline form.
  • the compound of formula (I) can form acid addition salts thereof. It will be appreciated that for use in therapy the salts of the compound of formula (I) should be pharmaceutically acceptable. Suitable pharmaceutically acceptable salts will be apparent to those skilled in the art and include those described in J. Pharm. Sci., 1977, 66, 1-19, such as acid addition salts formed with inorganic acids e.g. hydrochloric, hydrobromic, sulfuric, nitric or phosphoric acid; and organic acids e.g.
  • the compound of formula (I) may form acid addition salts with one or more equivalents of the acid.
  • the present invention includes within its scope all possible stoichiometric and non-stoichiometric forms.
  • the compound of formula (I) can be converted into a pharmaceutically acceptable addition salt by reaction with the appropriate organic or mineral acid.
  • Solvates of the compound of formula (I), including hydrates, are included within the scope of the invention.
  • Solvates of the compound of formula (I) may be formed by crystallization or recrystallization from the appropriate solvent.
  • hydrates may be formed by crystallization or recrystallization from aqueous solutions, or from aqueous organic solvents, i.e. organic solvents containing water.
  • This invention includes within its scope stoichiometric hydrates or solvates as well as compounds containing variable amounts of water and/or solvent.
  • Solvates of a compound of formula (I) which are suitable for use in therapy are those wherein the associated solvent is pharmaceutically acceptable.
  • Salts and solvates having non-pharmaceutically acceptable counterions or associated solvents are within the scope of the present invention, for example, for use as intermediates in the preparation of the compound of formula (I) and its pharmaceutically acceptable salts and solvates.
  • the compound of formula (I) has been shown to have NK 3 antagonistic activity and NK 3 selectivity. Such activity and selectivity may be demonstrated by the measurement of NK binding affinity via a scintillation proximity assay (SPA) as described in the experimental section below, or by published methods (as described or referenced in H. M. Sarau et al, J. Pharmacol. Experimental Therapeutics 1997, 281(3), 1303-1311; H. M. Sarau et al, J. Pharmacol. Experimental Therapeutics 2000, 295(1), 373-381 ; G. A. M. Giardina et al J.Med.Chem 1999, 42, 1053-1065).
  • SPA scintillation proximity assay
  • the invention therefore provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for use in therapy, in particular in human medicine.
  • the compound of formula (I) and salts and solvates thereof may be useful in the treatment of CNS disorders such as depression (which term includes bipolar (manic) depression (including type I and type II), unipolar depression, single or recurrent major depressive episodes with or without psychotic features, catatonic features, melancholic features, atypical features (e.g.
  • a general medical condition including, but not limited to, myocardial infarction, diabetes, miscarriage or abortion); anxiety disorders (including generalised anxiety disorder (GAD), social anxiety disorder (SAD), agitation, tension, social or emotional withdrawal in psychotic patients, panic disorder, and obsessive compulsive disorder); phobias (including agoraphobia and social phobia); psychosis and psychotic disorders (including schizophrenia,, schizo-affective disorder, schizophreniform-diseases,- acute psychosis, alcohol psychosis, autism, delerium, mania (including acute mania), manic depressive psychosis, hallucination, endogenous psychosis, organic psychosyndrome, paranoid and delusional disorders, puerperal psychosis, and psychosis associated with a general medical condition including, but not limited to, myocardial infarction, diabetes, miscarriage or abortion); anxiety disorders (including generalised anxiety disorder (GAD), social anxiety disorder (SAD), agitation, tension
  • cognitivosive disorders such as epilepsy (which includes simple partial seizures, complex partial seizures, secondary generalised seizures, generalised seizures including absence seizures, myoclonic seizures, clonic seizures, tonic seizures, tonic clonic seizures and atonic seizures); psychosexual dysfunction (including inhibited sexual desire (low libido), inhibited sexual arousal or excitement, orgasm dysfunction, inhibited female orgasm and inhibited male orgasm, hypoactive sexual desire disorder (HSDD), female sexual desire disorder (FSDD), and sexual dysfunction side-effects induced by treatment with a ⁇ tidepressants of the SSRI- class
  • musculoskeletal pain, post operative pain and surgical pain inflammatory pain and chronic pain
  • pain associated with normally non-painful sensations such as "pins and needles" (paraesthesias and dysesthesias), increased sensitivity to touch (hyperesthesia), painful sensation following innocuous stimulation (dynamic, static or thermal allodynia), increased, sensitivity, to noxious stimuli (thermal, cold, mechanical hyperalgesia), continuing pain sensation after removal of the stimulation (hyperpathia) or an absence of or deficit in selective sensory pathways (hypoalgesia), pain associated with migrane, and non-cardiac chest pain); and certain CNS-mediated disorders such as emesis, irritable bowel syndrome, and non-ulcer dyspepsia.
  • the compounds of the invention are useful for the treatment of depression; anxiety disorders; phobias; psychosis and psychotic disorders; post-traumatic stress disorder; attention deficit hyperactive disorder (ADHD); withdrawal from abuse of drugs including smoking cessation or reduction in level or frequency of such activities; and irritable bowel syndrome.
  • depression anxiety disorders; phobias; psychosis and psychotic disorders; post-traumatic stress disorder; attention deficit hyperactive disorder (ADHD); withdrawal from abuse of drugs including smoking cessation or reduction in level or frequency of such activities; and irritable bowel syndrome.
  • ADHD attention deficit hyperactive disorder
  • the compounds of the invention are useful for the treatment of depression; anxiety disorders; phobias; and psychosis and psychotic disorders (especially schizophrenia, schizo-affective disorder, and schizophreniform diseases.
  • a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the preparation of a medicament for use in the treatment of depression; anxiety disorders; phobias; psychosis and psychotic disorders; post-traumatic stress disorder; attention deficit hyperactive disorder (ADHD); cognitive impairment; convulsive disorders; psychosexual dysfunction; sleep disorders; disorders of eating behaviours; neurodegenerative diseases; withdrawal from abuse of drugs including smoking cessation or reduction in level or frequency of such activities; pain; emesis; irritable bowel syndrome; and non-ulcer dyspepsia.
  • ADHD attention deficit hyperactive disorder
  • a method for the treatment of a mammal comprising administration of an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in particular in the treatment of depression; anxiety,disorders;. phobias; psychosis and psychotic disorders; post-traumatic stress disorder; attention deficit hyperactive disorder (ADHD); cognitive impairment; convulsive disorders; psychosexual dysfunction; sleep disorders; disorders of eating behaviours; neurodegenerative diseases; withdrawal from abuse of drugs including smoking cessation or reduction in level or frequency of such activities; pain; emesis; irritable bowel syndrome; and non-ulcer dyspepsia.
  • a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in particular in the treatment of depression; anxiety,disorders;. phobias; psychosis and psychotic disorders; post-traumatic stress disorder; attention deficit hyperactive disorder (ADHD); cognitive impairment; convulsive disorders; psychosexual dysfunction; sleep disorders; disorders of eating behaviours; neurodegenerative diseases; withdrawal from abuse of drugs including
  • references herein to "treatment” extend to prophylaxis, prevention of recurrence and suppression or amelioration of symptoms (whether mild, moderate or severe) as well as the treatment of established conditions.
  • the compound of formula (I) may be administered as the raw chemical but the active ingredient is preferably presented as a pharmaceutical formulation.
  • the present invention further provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, in association with one or more pharmaceutically acceptable carrier(s), diluents(s) and/or excipient(s).
  • the carrier, diluent and/or excipient must be "acceptable” in the sense of being compatible with the other ingredients of the composition and not deletrious to the receipient thereof.
  • a process of preparing a pharmaceutical composition comprises mixing a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, together with a pharmaceutically acceptable carrier, diluent and/or excipient.
  • a compound of formula (I) or pharmeceutically acceptable salt or solvate thereof may be formulated for oral, buccal, parenteral, transdermal; topical (including ophthalmic and nasal), depot or rectal administration or in a form suitable for administration by inhalation or insufflation (either through the mouth or nose).
  • the pharmaceutical compositions may take the form of, for example, tablets, capsules, lozenges, sachets, vials, granules, powders or reconstituted powders, prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g. pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g. lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g. magnesium stearate, talc or silica); disintegrants (e.g. potato starch or sodium starch glycollate); or wetting agents (e.g. sodium lauryl sulphate).
  • binding agents e.g. pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose
  • fillers e.g. lactose, microcrystalline cellulose or calcium hydrogen phosphate
  • lubricants e.g. magnesium stea
  • the tablets may be coated by methods well known.
  • the ar Liquid preparations for oral administration may take the form of, for example, solutions, suspensions, syrups or suspensions or they may be presented as a dry product for constitution with water or other suitable vehicles before use.
  • Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g. lecithin or acacia); non-aqueous vehicles (e.g. almond oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g. methyl or propyl-p-hydroxybenzoates or sorbic acid).
  • the preparations may also contain buffer salts, flavouring, colouring and sweetening agents as appropriate.
  • Preparations for oral administration may be suitably formulated to give controlled release of the active compound.
  • compositions may take the form of tablets or lozenges formulated in a conventional manner.
  • the compound according to the present invention may be formulated for parenteral administration by injection, e.g. by bolus injection or continuous infusion.
  • Formulations for injection may be presented in unit dosage form, e.g. in ampoules or in multi-dose containers, with an added preservative.
  • the compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilising and/or dispersing agents.
  • the active ingredient may be in powder form for constitution with a suitable vehicle, e.g. sterile pyrogen-free water, before use.
  • the compound according to the present invention may be formulated for topical administration by insufflation and inhalation.
  • examples of types of preparation for topical administration include sprays and aerosols for use in an inhaler or insufflator.
  • Powders for external application may be formed with the aid of any suitable powder base, for example, lactose, talc or starch.
  • Spray compositions may be formulated as aqueous solutions or suspensions or as aerosols delivered from pressurised packs, such as metered dose inhalers, with the use of a suitable propellant.
  • the compound according to the present invention may also be formulated in rectal compositions such as suppositories or retention enemas, e.g. containing conventional suppository bases such as cocoa butter or other glycerides.
  • the compound may also be formulated as a depot preparation.
  • Such long acting formulations may be administered by implantation (for example subcutaneously, transcutaneously or intramuscularly) or by intramuscular injection.
  • the compound according to the present invention may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
  • a pharmaceutical composition of the invention is in unit dosage form and in a form adapted for use in the medical or veterinarial fields.
  • preparations may be in a pack form accompanied by written or printed instructions for use as an agent in the treatment of the conditions.
  • the daily dose of the compound of formula (I) or of a pharmaceutically acceptable salt or solvate thereof will depend on several factors such as the seriousness of the disease, the individual response of the patient, the kind of formulation or the route of admninstration, but it is usually comprised between 0.05mg and 10 mg per kg of body weight divided into a single dose or into more daily doses, e.g. 2, 3 or 4 times daily.
  • the total daily dose will normally be in the range of 5 to 500 mg, more preferred 5 to 200mg.
  • the unit dose may contain from 1 to 500 mg, in particular 2.5, 5, 7.5, 10, 15, 20, 50, 100, 150, or 200, 250, 300, 350, 400, 450 or 500 mg, more preferred being those dosages less than or equal to 200mg.
  • the compound of formula (I) and pharmaceutically acceptable salts or solvates thereof may be prepared by the processes described hereinafter, said processes constituting a further aspect of the invention.
  • a process (A) for preparing a compound of formula (I) as defined above or a salt or solvate thereof comprises reacting a compound of formula (II) or an activated derivative thereof with a compound of formula (III) (of S-stereochemistry at the chiral centre illustrated (*) or a racemate):
  • the compound of formula (II) is present as an activated derivative.
  • a suitable activated derivative is a transient activated form of a compound of formula (II) where the carboxylic acid group has been replaced by e.g. an acyl halide (preferably chloride) or a mixed anhydride.
  • a compound of formula (II) can be:
  • protecting groups used in the preparation of the compound of formula (I) may be used in a conventional manner. See for example Protective Groups in Organic Chemistry, Ed. J.F.W. McOmie, Plenum Press, London (1973) or Protective Groups in Organic Synthesis, Theodora Green, John Wiley and Sons, New York (1981).
  • suitable amino protecting groups include acyl type protecting groups (e.g. formyl, trifluoroacetyl, acetyl), aromatic urethane type protecting groups (e.g.
  • suitable oxygen protecting groups may include for example alky silyl groups, e.g. trimethylsilyl or tert-butyldimethylsilyl; alkyl ethers e.g. tetrahydropyranyl or tert-butyl; or esters e.g. acetate.
  • the therapeutic potential of the compounds of the present invention in treating the conditions can be assessed, for example, by measurement of brain penetration and ex vivo NK-3 receptor occupancy, or by measurement of the reversal of NK-3 agonist driven behaviours (e.g. contralateral turning in gerbils as described in Life Sciences 1995, 56, PL27-PL32 and Can. J. Physiol. Pharmacol. 2002, 80, 482-488; or guinea pig wet dog shakes as described in Br. J. Pharmacol. 1997, 122, 715-725) or by mechanistic correlates (e.g. electrophysiology of the dopamine cell firing as described in Gueudet et al., Synapse, 1999, 33, 71-79).
  • mechanistic correlates e.g. electrophysiology of the dopamine cell firing as described in Gueudet et al., Synapse, 1999, 33, 71-79.
  • NK binding affinity 125 l Substance P, 125 l NKA and 125 l [MePhe7]-NKB were used in the binding scintillation proximity assay (SPA) of NK1 , NK2 and NK3 receptor, respectively.
  • Polystrene Leadseeker WGA-SPA beads (Amersham Biosciences) were mixed with plasma membrane prepared from CHO cell lines expressing NK-1 , NK-2 or NK-3 in a bead/membrane ratio of 20:1 (w/w) in assay buffer (75mM Tris pH 7.8, 75mM NaCI, 4mM MnCI 2 , 1mM EDTA, 0.05% Chaps, 1mM PMSF).
  • the compound of formula (I) has been shown to have the following advantageous properties, by reference to various of the assay/studies described above:
  • Example The following non-limiting example illustrates aspects of the present invention.
  • M molar
  • M millimolar
  • i. v. intravenous
  • Hz Hertz
  • T r retention time
  • RP reverse phase
  • TEA triethylamine
  • TFA trifluoroacetic acid
  • TFAA trifluoroacetic anhydride
  • THF tetrahydrofuran
  • DCE dichloroethane
  • DMF ⁇ /, ⁇ /-dimethylformamide
  • IBCF isobutyl chloroformate
  • HOAc acetic acid
  • HOSu ⁇ iydroxysuccinimide
  • HOBT 1-hydroxybenzotriazole
  • mCPBA metal-chloroperbenzoic acid
  • EDC ethylcarbodiimide hydrochloride
  • DCC (dicyclohexylcarbodiimide); CBZ (benzyloxycarbonyl);
  • TIPS triisopropylsilyl
  • TBS f-butyldimethylsilyl
  • Example 1 3-Amino-2-(4-fluoro-phenyl)-guinoline-4-carboxylic acid ((S)-l-phenyl-propyl)- amide

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

Abstract

L'invention concerne un composé de formule (I) ou un sel pharmaceutiquement acceptable ou un solvate dudit composé. Elle concerne également des méthodes de préparation et d'utilisation dudit composé à des fins thérapeutiques, notamment pour le traitement du SNC ou de troubles induits par le SNC.
PCT/EP2003/013796 2002-12-04 2003-12-02 Derives d'amide quinoleique utilises comme agents contre des troubles du snc WO2004050627A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003292196A AU2003292196A1 (en) 2002-12-04 2003-12-02 A quinoline amide derivative as agent against disorders of the cns

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0228288.7 2002-12-04
GBGB0228288.7A GB0228288D0 (en) 2002-12-04 2002-12-04 Chemical compounds

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WO2004050627A1 true WO2004050627A1 (fr) 2004-06-17

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006013394A1 (fr) * 2004-08-06 2006-02-09 Merck Sharp & Dohme Limited Dérivés de quinoleine tels que les antagonistes du récepteur de la neurokinine
WO2007012900A1 (fr) 2005-07-29 2007-02-01 Merck Sharp & Dohme Limited Dérivés de la quinoline en tant qu’antagonistes des récepteurs de la neurokinine
US7608628B2 (en) 2005-12-12 2009-10-27 Astrazeneca Ab Alkylsulphonamide quinolines
US9475773B2 (en) 2013-04-19 2016-10-25 Astrazeneca Ab NK3 receptor antagonist compound (NK3RA) for use in a method for the treatment of polycystic ovary syndrome (PCOS)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995032948A1 (fr) * 1994-05-27 1995-12-07 Smithkline Beecham Farmaceutici S.P.A. Derives de quinoline utilises comme antagonistes du recepteur nk3 de la tachykinine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995032948A1 (fr) * 1994-05-27 1995-12-07 Smithkline Beecham Farmaceutici S.P.A. Derives de quinoline utilises comme antagonistes du recepteur nk3 de la tachykinine

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006013394A1 (fr) * 2004-08-06 2006-02-09 Merck Sharp & Dohme Limited Dérivés de quinoleine tels que les antagonistes du récepteur de la neurokinine
WO2007012900A1 (fr) 2005-07-29 2007-02-01 Merck Sharp & Dohme Limited Dérivés de la quinoline en tant qu’antagonistes des récepteurs de la neurokinine
US7608628B2 (en) 2005-12-12 2009-10-27 Astrazeneca Ab Alkylsulphonamide quinolines
US8071621B2 (en) 2005-12-12 2011-12-06 Astrazeneca Ab Alkylsulphonamide quinolines
US9475773B2 (en) 2013-04-19 2016-10-25 Astrazeneca Ab NK3 receptor antagonist compound (NK3RA) for use in a method for the treatment of polycystic ovary syndrome (PCOS)

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AU2003292196A1 (en) 2004-06-23

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