AR037080A1 - Compuestos utiles en el tratamiento de enfermedades inflamatorias,composiciones que los contienen, su uso en terapia, metodos de tratamiento, procesos de preparacion e intermediarios - Google Patents

Compuestos utiles en el tratamiento de enfermedades inflamatorias,composiciones que los contienen, su uso en terapia, metodos de tratamiento, procesos de preparacion e intermediarios

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Publication number
AR037080A1
AR037080A1 ARP010104603A ARP010104603A AR037080A1 AR 037080 A1 AR037080 A1 AR 037080A1 AR P010104603 A ARP010104603 A AR P010104603A AR P010104603 A ARP010104603 A AR P010104603A AR 037080 A1 AR037080 A1 AR 037080A1
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AR
Argentina
Prior art keywords
alkyl
aryl
heteroaryl
group
formula
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ARP010104603A
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English (en)
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Glaxo Group Ltd
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Publication date
Priority claimed from GB0023973A external-priority patent/GB0023973D0/en
Priority claimed from GB0107643A external-priority patent/GB0107643D0/en
Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd
Publication of AR037080A1 publication Critical patent/AR037080A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
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    • 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
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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
    • A61P25/28—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
    • 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
    • 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
    • A61P3/08—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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A61P33/12—Schistosomicides
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
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    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
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    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D267/02—Seven-membered rings
    • C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
    • C07D267/10—Seven-membered rings having the hetero atoms in positions 1 and 4 not condensed with other rings
    • 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
    • C07D413/06—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 linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D413/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Neurology (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Pain & Pain Management (AREA)
  • Obesity (AREA)
  • Communicable Diseases (AREA)
  • Hospice & Palliative Care (AREA)
  • Emergency Medicine (AREA)
  • Transplantation (AREA)
  • Psychiatry (AREA)
  • Ophthalmology & Optometry (AREA)
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Abstract

Compuestos de la fórmula (1), en la que: R1 representa alquilo C1-6, alquenilo C2-6, alquinilo C2-6, aril-Y1-, heteroaril-Y1-, aril-(O)t-aril-Y1, aril-(O)t-heteroaril-Y1-, heteroaril-(O)t-aril-Y1-, heteroaril-(O)t-heteroaril-Y1-, aril-SO2-Y1-, (alquil C1-6)-G-Y1-, heteroaril-G-aril-Y1-, J1-SO2-Y1-, R17O(CO)-(alquenil C2-6)-Y1-, R17NHCO-Y1-, R17NHSO2-Y1-, (alquinil C2-6)-Y1-, (alquenil C2-6)-Y1-, aril-O-Y1-, heteroaril-O-Y1-, (alquil C1-6)-SO2-Y1-, M-Y1-, J1-Y1-, J1-CO-Y1-, aril-CO-Y1- ó (cicloalquil C3-8)-Y1- ó (cicloalquenil C3-8)-Y1-; cuyos grupos alquinilo C2-6 y (alquinil C2-6)-Y1 pueden estar opcionalmente sustituidos con un grupo -OR17, cuyo grupo alquenilo C2-6 puede estar opcionalmente sustituido con uno o más grupos -COOR17, y cuyos grupos cicloalquilo o cicloalquenilo pueden estar opcionalmente sustituidos con uno o más grupos hidroxilo o alquilo C1-6; R2 representa hidrógeno o alquilo C1-6 opcionalmente sustituido con un grupo hidroxilo; R3 representa hidrógeno o alquilo C1-6; ó R1 y R2 pueden, conjuntamente con el átomo de nitrógeno al cual están unidos, formar un grupo de la fórmula J2, en donde el átomo de nitrógeno sustituya ya sea a X1 ó X2; t representa 0 ó 1; X representa etileno o un grupo de la fórmula CReRf donde Re y Rf independientemente representan hidrógeno o alquilo C1-4, ó Re y Rf pueden, conjuntamente con el átomo de carbono al cual están unidos, formar un grupo cicloalquilo C3-8; R4 y R5 representan independientemente hidrógeno o alquilo C1-4; Z representa un enlace, CO, SO2, CR10R7(CH2)n, (CH2)nCR10R7, CHR7(CH2)nO, CHR7(CH2)nS, CHR7(CH2)nOCO, CHR7(CH2)nCO, COCHR7(CH2)n ó S2CHR7(CH2)n; R6 representa alquilo C1-6, alquenilo C2-6, aril heteroarilo, aril-(alquenilo C2-6)-, -CN ó un grupo de la fórmula -Y2-J3; R7 representa hidrógeno, alquilo C1-4, CONR8R9 ó COO (alquilo C1-8); a y b representan 1 ó 2, tal que a + b representa 2 ó 3; G representa -SO2-, -SO2NR18, -NR18SO2-, -NR18CO-, CO ó -CONR18-; n representa un número entero de 0 a 4; M representa un grupo cicloalquilo C3-8 ó cicloalquenilo C3-8 fusionado a un grupo arilo monocíclico o heteroarilo monocíclico; J1, J2 y J3 independientemente representan una porción de la fórmula (2) en donde X1 representa oxígeno, NR11 ó azufre, X2 representa CH2, oxígeno, NR12 ó azufre, m1 representa un número entero de 1 a 3 y m2 representa un número entero de 1 a 3; con la condición de que m1 + m2 esté en el intervalo de 3 a 5, también con la condición de que cuando X1 y X2 representen oxígeno, NR11, NR12 o azufre, m1 y m2 deben ambos no ser menor de 2, en donde la fórmula 2 está opcionalmente sustituida con uno o más (por ejemplo 1 ó 2) grupos -Y3-arilo, -Y3-heteroarilo, -Y3-CO-arilo, -CO(cicloalquilo C3-8), -Y3-CO-heteroarilo, -alquilo C1-6, -Y3-COO (alquilo C1-6), -Y3-CO(alquilo C1-6), -Y3-W, -Y3-CO-W-, -Y3-NR15R16, -Y3-CONR15R16, hidroxilo, oxo, -Y3-SO2NR15R16, -Y3-SO2(alquilo C1-6), -Y3-SO2-arilo, -Y3-SO2heteroarilo, -Y3-NR13 (alquilo C1-6), -Y3-NR13SO2 (alquilo C1-6), -Y3-NR13CONR15R16, -Y3-NR13COOR14 ó -Y3-OCONR15R16, y está opcionalmente fusionado a un anillo arilo o heteroarilo monocíclicos; R8, R9, R10, R11, R12, R13 y R14 independientemente representan hidrógeno o alquilo C1-6; R15 y R16 representan independientemente hidrógeno o alquilo C1-6 o R15 y R16 conjuntamente con el átomo de nitrógeno al cual están unidos pueden formar un anillo de morfolina, piperidina o pirrolidina; R17 y R18 independientemente representan hidrógeno ó alquilo C1-6; W representa un anillo saturado o insaturado, no aromático de 5 a 7 miembros, que contiene entre 1 y 3 heteroátomos seleccionados de nitrógeno, oxígeno o azufre; opcionalmente sustituidos con uno o más grupos alquilo C1-6, halógeno o hidroxilo; Y1, Y2 e Y3 representan independientemente un enlace o un grupo de la fórmula -(CH2)pCRcRd(CH2)q- en donde Rc y Rd representan independientemente hidrógeno ó alquilo C1-4, ó Rc y Rd pueden, conjuntamente con el átomo de carbono al cual están unidos, formar un grupo cicloalquilo C3-8 y p y q representan independientemente un número entero de 0 a 5 en donde p + q es un número entero de 0 a 5; con la condición de que el compuesto de la fórmula (1) no sea un compuesto de la fórmula (3), en donde R2' representa hidrógeno o alquilo C1-4; R3' representa hidrógeno; X' representa metileno o etileno; a' y b' ambos representan 1; R4' y R5' ambos representan hidrógeno; y en donde la porción -Z'-R6' representa halobencilo; y las sales y solvatos de los mismos; los procesos para la preparación de los mismos, las composiciones que los contienen, su uso en terapia para el tratamiento de enfermedades inflamatorios, métodos de tratamiento, proceso de preparación e intermediarios.
ARP010104603A 2000-09-29 2001-09-28 Compuestos utiles en el tratamiento de enfermedades inflamatorias,composiciones que los contienen, su uso en terapia, metodos de tratamiento, procesos de preparacion e intermediarios AR037080A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0023973A GB0023973D0 (en) 2000-09-29 2000-09-29 Therapeutically useful compounds
GB0107643A GB0107643D0 (en) 2001-03-27 2001-03-27 Therapeutically useful compounds

Publications (1)

Publication Number Publication Date
AR037080A1 true AR037080A1 (es) 2004-10-20

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ARP010104603A AR037080A1 (es) 2000-09-29 2001-09-28 Compuestos utiles en el tratamiento de enfermedades inflamatorias,composiciones que los contienen, su uso en terapia, metodos de tratamiento, procesos de preparacion e intermediarios

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US (1) US7157457B2 (es)
EP (2) EP1586567A1 (es)
JP (1) JP5069392B2 (es)
KR (1) KR20030040510A (es)
CN (1) CN1478084A (es)
AR (1) AR037080A1 (es)
AT (1) ATE345331T1 (es)
AU (1) AU2001290146A1 (es)
BR (1) BR0114321A (es)
CA (1) CA2423305A1 (es)
CZ (1) CZ20031194A3 (es)
DE (1) DE60124576T2 (es)
ES (1) ES2275729T3 (es)
HU (1) HUP0303107A2 (es)
IL (1) IL155092A0 (es)
MX (1) MXPA03002813A (es)
NO (1) NO20031443L (es)
NZ (1) NZ525055A (es)
PL (1) PL362984A1 (es)
WO (1) WO2002026723A1 (es)

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US6777399B2 (en) 2000-08-05 2004-08-17 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
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GB0207436D0 (en) * 2002-03-28 2002-05-08 Glaxo Group Ltd Novel compounds
TW200400035A (en) * 2002-03-28 2004-01-01 Glaxo Group Ltd Novel compounds
GB0207449D0 (en) * 2002-03-28 2002-05-08 Glaxo Group Ltd Novel compounds
GB0207432D0 (en) * 2002-03-28 2002-05-08 Glaxo Group Ltd Novel compounds
GB0207447D0 (en) * 2002-03-28 2002-05-08 Glaxo Group Ltd Novel compounds
GB0207439D0 (en) * 2002-03-28 2002-05-08 Glaxo Group Ltd Novel compounds
GB0211759D0 (en) * 2002-05-22 2002-07-03 Glaxo Group Ltd Novel compounds
GB0212357D0 (en) * 2002-05-29 2002-07-10 Glaxo Group Ltd Novel compounds
GB2389530B (en) 2002-06-14 2007-01-10 Cipla Ltd Pharmaceutical compositions
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EP1324991A1 (en) 2003-07-09
PL362984A1 (en) 2004-11-15
KR20030040510A (ko) 2003-05-22
US20040058907A1 (en) 2004-03-25
EP1586567A1 (en) 2005-10-19
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CA2423305A1 (en) 2002-04-04
IL155092A0 (en) 2003-10-31
ATE345331T1 (de) 2006-12-15
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BR0114321A (pt) 2003-07-01
CN1478084A (zh) 2004-02-25
DE60124576T2 (de) 2007-06-21
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WO2002026723A1 (en) 2002-04-04
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HUP0303107A2 (hu) 2004-03-01
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