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EP1076557A1 - Antagonistes du recepteur ccr-3 - Google Patents

Antagonistes du recepteur ccr-3

Info

Publication number
EP1076557A1
EP1076557A1 EP99920102A EP99920102A EP1076557A1 EP 1076557 A1 EP1076557 A1 EP 1076557A1 EP 99920102 A EP99920102 A EP 99920102A EP 99920102 A EP99920102 A EP 99920102A EP 1076557 A1 EP1076557 A1 EP 1076557A1
Authority
EP
European Patent Office
Prior art keywords
propionate
ethyl
hydroxyphenyl
sulfonylamino
group
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Withdrawn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
EP99920102A
Other languages
German (de)
English (en)
Inventor
Dashyant Dhanak
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.)
SmithKline Beecham Corp
Original Assignee
SmithKline Beecham Corp
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 SmithKline Beecham Corp filed Critical SmithKline Beecham Corp
Publication of EP1076557A1 publication Critical patent/EP1076557A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • 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
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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

Definitions

  • the present invention relates to the use of phenylalanine sulfonamide derivatives, and pharmaceutical compositions containing these compounds as Chemok ⁇ ne/CCR-3 receptor antagonists
  • Chemokines are a superfamily of small secreted proteins There are approximately 30 distinct chemokines known with many others being characte ⁇ zed See Oppenheim et al , Properties of the Novel Promflammatory Supergene "Interc ⁇ ne” Cytokine Family. Ann Rev Immun , 9, 617- 648 (1991), and Baggiolini, et al , Interleuk ⁇ n-8 and Related Chemotactic Cytokmes-CXC and CC Chemokines, Ad ⁇ Immun .
  • Eosinophils are promflammatory granulocytes that play a major role in allergic diseases, such as bronchial asthma, allergic rhinitis, pru ⁇ tis and atopic dermatitis Upon activation, eosinophils release hpid mediators, cytotoxic proteins, oxygen metabolites and cytokines, all of which have the potential to produce pathophysiology Numerous studies have demonstrated the presence of eosinophils or eosmophil-specific products in inflamed tissues in human diseases
  • Eotaxm a CC chemokine
  • T e human homologue of Guinea-pig eotaxm has been expressed and has been shown to induce eosmophil infiltration when injected into the skin of the rhesus monkey See Ponath, et al , Cloning of the Human Eosmophil Chemoattractant, Eotaxin Expression, Receptor Binding, and Functional Properties Suggest a Mechanism for Selective Recruitment of Eosinophils, J_ Chn Invest . 97, 604-612 (1996)
  • CCR-3 receptor is expressed at high levels on eosinophils; typically 40,000- 400,000 receptors per cell are present. This is 10-100 fold more than the other chemokine receptor (CCR-1) expressed in eosinophils.
  • CCR-1 chemokine receptor
  • Monoclonal antibodies raised to the CCR-3 receptor demonstrate that the receptor is primarily restricted to eosinophils and a subset of Th2 T-cells. This restricted expression on eosinophils and T-cells may be responsible for the selective recruitment of eosinophils and Th2 T- cells in allergic inflammation. Additionally, CCR-3 is potently activated by eotaxin 1, eotaxin and MCP-4.
  • chemokines appear to activate more than one chemokine receptor, e.g. RANTES binds to CCR- 1 , CCR-3, CCR-4 and CCR-5 receptors.
  • CCR-3 receptor antagonists thus offer a unique approach toward decreasing the pathophysiology associated with allergic diseases.
  • Antagonism of this receptor may be useful in the treatment of allergic disorders, including but not limited to bronchial asthma, allergic rhinitis, eczema, nasal polyposis, conjunctivitis, atopic dermatitis, inflammatory bowel disorder and pruritis.
  • the present invention involves phenylalanine sulfonamide derivatives represented by
  • Formula (I) hereinbelow and their use as CCR-3 receptor antagonists which is useful in the treatment of a variety of diseases associated with allergic disorders, including but not limited to bronchial asthma, eczema, allergic rhinitis, conjunctivitis, nasal polyposis, atopic dermatitis, pruritis and inflammatory bowel disease.
  • the present invention further provides methods for antagonizing CCR-3 receptors in an animal, including humans, which comprises administering to a subject in need of treatment an effective amount of a compound of Formula (I) as indicated hereinbelow.
  • R j represents substituted or unsubstituted alkyl, aryl or heteroaryl; and R2 is selected from the group consisting of 4-OH, 4-(2,5-Cl2-Ph)0, and 4-(2.4-F 2 -Ph)0.
  • Preferred alkyl moieties are C1.4 alkyl. most preferably methyl.
  • Preferred aryl moieties are phenyl or naphthyl, unsubstituted, monosubstituted, disubstituted or trisubstituted.
  • Preferred heteroaryl moieties are selected from the group consisting of unsubstituted. monosubstituted, disubstituted or trisubstituted thienyl, quinolinyl, and pyrazolyl.
  • alkyl substituents are methyl. More preferably, halo substituents are chloro or bromo.
  • Preferred compounds useful in the present invention are selected from the group consisting of:
  • More preferred compounds useful in the present invention include:
  • the most preferred compounds useful in the present invention include:
  • compositions of the present invention are pharmaceutically acceptable salt complexes.
  • Preferred are the ethylene diamine, sodium, potassium, calcium and ethanolamine salts.
  • the compounds of the present invention may contain one or more
  • compounds of the present invention are represented by the following structure:
  • the present compounds can be prepared by the using the overall strategies provided hereinbelow. Such strategies are readily found in the art. See e.g. Comprehensive Organic Transformations. R.C. Larock, VCH Publishers, 1989, 772 (and references therein); and Organic chemistry, Vol. 1 : 1. L. Finar, Longman Group, 1973, 406.
  • treatment includes, but is not limited to prevention, retardation and prophylaxis of the disease.
  • the present compounds are useful for the treatment of diseases including but not limited to bronchial asthma, eczema, allergic rhinitis, conjunctivitis, nasal polyposis, atopic dermatitis, pruritis and inflammatory bowel disease.
  • Compounds of Formula (I) and their pharmaceutically acceptable salts may be administered in a standard manner for the treatment of the indicated diseases, for example orally, parenterally, sub-lingually, dermally, transdermally, rectally, via inhalation or via buccal administration.
  • Composition of Formula (I) and their pharmaceutically acceptable salts which are active when given orally can be formulated as syrups, tablets, capsules, creams and lozenges.
  • a syrup formulation will generally consist of a suspension or solution of the compound or salt in a liquid carrier for example, ethanol, peanut oil. olive oil, glycerine or water with a flavoring or coloring agent. Where the composition is in the form of a tablet, any pharmaceutical carrier routinely used for preparing solid formulations may be used.
  • any routine encapsulation is suitable, for example using the aforementioned carriers in a hard gelatin capsule shell.
  • any pharmaceutical carrier routinely used for preparing dispersions or suspensions may be considered, for example aqueous gums, celluloses, silicates or oils, and are incorporated in a soft gelatin capsule shell.
  • Typical parenteral compositions consist of a solution or suspension of a compound or salt in a sterile aqueous or non-aqueous carrier optionally containing a parenterally acceptable oil, for example polyethylene glycol, polyvinylpyrrolidone, lecithin, arachis oil or sesame oil.
  • a parenterally acceptable oil for example polyethylene glycol, polyvinylpyrrolidone, lecithin, arachis oil or sesame oil.
  • compositions for inhalation are in the form of a solution, suspension or emulsion that may be administered as a dry powder or in the form of an aerosol using a conventional propellant such as dichlorodifluoromethane or trichlorofluoromethane.
  • a typical suppository formulation comprises a compound of Formula (I) or a pharmaceutically acceptable salt thereof which is active when administered in this way, with a binding and/or lubricating agent, for example polymeric glycols, gelatins, cocoa-butter or other low melting vegetable waxes or fats or their synthetic analogs.
  • Typical dermal and transdermal formulations comprise a conventional aqueous or non-aqueous vehicle, for example a cream, ointment, lotion or paste or are in the form of a medicated plaster, patch or membrane.
  • the composition is in unit dosage form, for example a tablet, capsule or metered aerosol dose, so that the patient may administer a single dose.
  • Each dosage unit for oral administration contains suitably from 0.1 mg to 500 mg/Kg, and preferably from 1 mg to 100 mg/Kg, and each dosage unit for parenteral administration contains suitably from 0 1 mg to 100 mg/Kg, of a compound of Formula(I) or a pharmaceutically acceptable salt thereof calculated as the free acid
  • Each dosage unit for mtranasal administration contains suitably 1-400 mg and preferably 10 to 200 mg per person
  • a topical formulation contains suitably 0.01 to 5.0% of a compound of Formula (I)
  • the daily dosage regimen for oral administration is suitably about 0 01 mg/Kg to 40 mg/Kg, of a compound of Formula(I) or a pharmaceutically acceptable salt thereof calculated as the free acid
  • the daily dosage regimen for parenteral administration is suitably about 0.001 mg/Kg to 40 mg/Kg, of a compound of Formula (I) or a pharmaceutically acceptable salt thereof calculated as the free acid
  • the daily dosage regimen for mtranasal administration and oral inhalation is suitably about 10 to about 500 mg/person
  • the active ingredient may be administered from 1 to 6 times a day, sufficient to exhibit the desired activity
  • Eosinophils Human eosinophils were pu ⁇ fied by standard CD 16 cell depletion using a Miltenyi cell separation column and a magnetic Super Macs magnet. Eosinophils which were >95% pure as assessed by DiffQuick staining and light microscopy were washed in PBS and resuspended m binding buffer (RPMI-1640 + 25mM Hepes + 0 1% Gelatin + 0 1% sodium azide + 00087c CHAPS) Into a 96 well plate (Dynatek) 200,000 eosinophils, 0.25 nM 1251-Eotax ⁇ n (Amersham Pic), and compound of interest ( 1 nM to 100 uM) was added.
  • RPMI-1640 + 25mM Hepes + 0 1% Gelatin + 0 1% sodium azide + 00087c CHAPS Into a 96 well plate (Dynatek) 200,000 eosinophils, 0.25 nM 1251
  • Bound from free 1251-eotaxm was separated using a Packard Filtermate 196, 96- well plate harvester To determine total and non-specific binding (NSB) three wells for each condition were set aside. For total binding and NSB, wells received all additions except compound. In addition NSB wells received 200 nM cold eotaxin (PeproTech, Rocky Hill, NJ). Radioactivity associated with the filter was assessed in a Packard Top-count Microplate Scintillation Counter model number 49872V Percent control binding was assessed by first subtracting the NSB from each well and then expressing
  • BALs were obtained from Guinea Pigs (+ compound) 24 h after ovalbumin (OA) exposure to eotaxin administered via inhalation.
  • the animals were euthanized by cervical dislocation and exsanguinated.
  • the lungs were lavaged with 50 ml of DulBecco's PBS (5x1 Occ), which was aspirated after a gentle chest massage.
  • the BAL fluid was spun down and the pellet was resuspended in 0.25% NaCl to lyse residual erythrocytes. After centrifugation, the pellet was resuspended again in 0.9% NaCl. After a total cell count, slides were prepared and stained.
  • the cells were differentiated into eosinophils, neutrophils and monocytes by counting a minimum of 200 cells and expressing the results as a percentage of total cells.
  • OA sensitized Guinea Pigs (+ compound) were exposed to OA via inhalation
  • EXAMPLE 2 Inhalant Formulation A compound of Formula I, (1 mg to 100 mg) is aerosolized from a metered dose inhaler to deliver the desired amount of drug per use.
  • a pharmaceutical composition for parenteral administration is prepared by dissolving an appropriate amount of a compound of Formula I in polyethylene glycol with heating. This solution is then diluted with water for injections Ph Eur. (to 100 ml). The solution is then rendered sterile by filtration through a 0.22 micron membrane filter and sealed in sterile containers.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Immunology (AREA)
  • Emergency Medicine (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des antagonistes du récepteur CCR-3, ainsi que de nouveaux procédés permettant d'utiliser ces antagonistes.
EP99920102A 1998-04-27 1999-04-27 Antagonistes du recepteur ccr-3 Withdrawn EP1076557A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US8322898P 1998-04-27 1998-04-27
US83228P 1998-04-27
PCT/US1999/009182 WO1999055324A1 (fr) 1998-04-27 1999-04-27 Antagonistes du recepteur ccr-3

Publications (1)

Publication Number Publication Date
EP1076557A1 true EP1076557A1 (fr) 2001-02-21

Family

ID=22177004

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99920102A Withdrawn EP1076557A1 (fr) 1998-04-27 1999-04-27 Antagonistes du recepteur ccr-3

Country Status (4)

Country Link
EP (1) EP1076557A1 (fr)
JP (1) JP2002512957A (fr)
CA (1) CA2329777A1 (fr)
WO (1) WO1999055324A1 (fr)

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WO2000041685A1 (fr) * 1999-01-19 2000-07-20 Smithkline Beecham Corporation Antagonistes des recepteurs ccr-3
CA2423251A1 (fr) 2000-09-29 2002-04-04 Glaxo Group Limited Derives de morpholine-acetamide permettant de traiter les maladies inflammatoires
US7115635B2 (en) 2001-04-27 2006-10-03 Mitsubishi Pharma Corporation Benzylpiperidine compound
JP2003081937A (ja) * 2001-09-07 2003-03-19 Bayer Ag ベンゼンスルホンアミド誘導体
EP1481967B1 (fr) * 2002-03-05 2011-05-04 Sumitomo Chemical Company, Limited Procede de preparation de composes biaryle
SE0200843D0 (sv) 2002-03-19 2002-03-19 Astrazeneca Ab Chemical compounds
NZ566263A (en) 2002-05-24 2009-09-25 Millennium Pharm Inc CCR9 inhibitors and methods of use thereof
ATE363470T1 (de) 2002-11-18 2007-06-15 Chemocentryx Inc Arylsulfonamide
US7741519B2 (en) 2007-04-23 2010-06-22 Chemocentryx, Inc. Bis-aryl sulfonamides
US7227035B2 (en) 2002-11-18 2007-06-05 Chemocentryx Bis-aryl sulfonamides
US7420055B2 (en) 2002-11-18 2008-09-02 Chemocentryx, Inc. Aryl sulfonamides
EP2385040A1 (fr) 2003-03-14 2011-11-09 ONO Pharmaceutical Co., Ltd. Dérivés hétérocycliques renfermant de l'azote et médicaments contenant ces dérivés comme principe actif
ATE413178T1 (de) 2003-03-24 2008-11-15 Actimis Pharmaceuticals Inc 2-phenoxy- und 2-phenylsulfanyl-benzenesulfonamid derivate mit ccr3 antagonistischer aktivität zur behandlung von asthma und anderen entzündlichen oder immunologischen erkrankungen
SE0300957D0 (sv) 2003-04-01 2003-04-01 Astrazeneca Ab Chemical compounds
US7498323B2 (en) 2003-04-18 2009-03-03 Ono Pharmaceuticals Co., Ltd. Spiro-piperidine compounds and medicinal use thereof
KR101011848B1 (ko) 2004-09-08 2011-02-01 미쓰비시 타나베 파마 코퍼레이션 모르폴린 화합물
WO2006030925A1 (fr) 2004-09-13 2006-03-23 Ono Pharmaceutical Co., Ltd. Derive heterocyclique azote et medicament le contenant en tant que principe actif
EP1889622A4 (fr) 2005-05-31 2009-12-23 Ono Pharmaceutical Co Compose de spiropiperidine et son utilisation medicinale
JP2009501793A (ja) 2005-07-21 2009-01-22 アストラゼネカ・アクチエボラーグ 新規ピペリジン誘導体
JP5251127B2 (ja) 2005-10-28 2013-07-31 小野薬品工業株式会社 塩基性基を含有する化合物およびその用途
PL1961744T3 (pl) 2005-11-18 2013-09-30 Ono Pharmaceutical Co Związek zawierający grupę zasadową oraz jego zastosowanie
US8003642B2 (en) 2006-03-10 2011-08-23 Ono Pharmaceutical Co., Ltd. Nitrogenated heterocyclic derivative, and pharmaceutical agent comprising the derivative as active ingredient
EP2042503B1 (fr) 2006-05-16 2013-01-30 Ono Pharmaceutical Co., Ltd. Composé ayant un groupe acide qui peut être protégé et utilisation dudit composé
EP2055705A4 (fr) 2006-07-31 2014-08-20 Ono Pharmaceutical Co Composé auquel un groupe cyclique est lié par une liaison spiro et son utilisation
WO2010129351A1 (fr) 2009-04-28 2010-11-11 Schepens Eye Research Institute Procédé pour identifier et pour traiter une dégénérescence maculaire liée à l'âge
US8741894B2 (en) 2010-03-17 2014-06-03 Axikin Pharmaceuticals, Inc. Arylsulfonamide CCR3 antagonists

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JPH09255572A (ja) * 1996-03-26 1997-09-30 Takeda Chem Ind Ltd ケモカイン受容体拮抗剤

Non-Patent Citations (1)

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Also Published As

Publication number Publication date
JP2002512957A (ja) 2002-05-08
WO1999055324A1 (fr) 1999-11-04
CA2329777A1 (fr) 1999-11-04

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