SI1476438T1 - Oksa- in tiadiazoli in njihova uporaba kot inhibitorji metaloproteinaze - Google Patents

Oksa- in tiadiazoli in njihova uporaba kot inhibitorji metaloproteinaze

Info

Publication number
SI1476438T1
SI1476438T1 SI200330870T SI200330870T SI1476438T1 SI 1476438 T1 SI1476438 T1 SI 1476438T1 SI 200330870 T SI200330870 T SI 200330870T SI 200330870 T SI200330870 T SI 200330870T SI 1476438 T1 SI1476438 T1 SI 1476438T1
Authority
SI
Slovenia
Prior art keywords
thiadiazoles
oxa
metalloproteinase inhibitors
inhibitors
oproteinases
Prior art date
Application number
SI200330870T
Other languages
English (en)
Inventor
A P British Biotech P Ayscough
S J British Biotech Pha Davies
Gilles British Biotech Ph Pain
Jean-Yves Gillon
Original Assignee
Serono Lab
Vernalis R&D Ltd
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 Serono Lab, Vernalis R&D Ltd filed Critical Serono Lab
Publication of SI1476438T1 publication Critical patent/SI1476438T1/sl

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D271/00Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/061,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/08Bronchodilators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/02Drugs for disorders of the nervous system for peripheral neuropathies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D285/00Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01Five-membered rings
    • C07D285/02Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/081,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/06Heterocyclic 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Virology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Communicable Diseases (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Vascular Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Transplantation (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
SI200330870T 2002-02-22 2003-02-20 Oksa- in tiadiazoli in njihova uporaba kot inhibitorji metaloproteinaze SI1476438T1 (sl)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0204159.8A GB0204159D0 (en) 2002-02-22 2002-02-22 Metalloproteinase inhibitors
PCT/GB2003/000741 WO2003070711A1 (en) 2002-02-22 2003-02-20 Oxa- and thiadiazoles and their use as metalloproteinase inhibitors

Publications (1)

Publication Number Publication Date
SI1476438T1 true SI1476438T1 (sl) 2007-10-31

Family

ID=9931543

Family Applications (1)

Application Number Title Priority Date Filing Date
SI200330870T SI1476438T1 (sl) 2002-02-22 2003-02-20 Oksa- in tiadiazoli in njihova uporaba kot inhibitorji metaloproteinaze

Country Status (27)

Country Link
US (4) US7358265B2 (sl)
EP (1) EP1476438B1 (sl)
JP (1) JP4615864B2 (sl)
KR (1) KR101098614B1 (sl)
CN (1) CN100351245C (sl)
AT (1) ATE360007T1 (sl)
AU (1) AU2003205910B2 (sl)
BR (1) BR0307899A (sl)
CA (1) CA2475867C (sl)
CY (1) CY1106730T1 (sl)
DE (1) DE60313292T2 (sl)
DK (1) DK1476438T3 (sl)
EA (1) EA007609B1 (sl)
ES (1) ES2286404T3 (sl)
GB (1) GB0204159D0 (sl)
HK (1) HK1078583A1 (sl)
HR (1) HRP20040725A2 (sl)
IL (1) IL163413A (sl)
MX (1) MXPA04008132A (sl)
NO (1) NO330772B1 (sl)
PL (1) PL210773B1 (sl)
PT (1) PT1476438E (sl)
RS (1) RS51354B (sl)
SI (1) SI1476438T1 (sl)
UA (1) UA78275C2 (sl)
WO (1) WO2003070711A1 (sl)
ZA (1) ZA200406755B (sl)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004101537A1 (en) * 2003-05-17 2004-11-25 British Biotech Pharmaceuticals Ltd Metalloproteinase inhibitors
DE602004032548D1 (de) * 2003-08-23 2011-06-16 Merck Serono Sa Derivate von hydroxamsäure als metalloproteinaseinhibitoren
US7838522B2 (en) 2004-11-17 2010-11-23 Ares Trading S.A. Benzothiazole formulations and use thereof
JP5021488B2 (ja) 2004-12-21 2012-09-05 メルク セローノ ソシエテ アノニム スルホニルアミノ環式誘導体及びその使用
DK1844032T3 (da) 2005-01-31 2011-10-24 Merck Serono Sa N-hydroxyamid-derivater og deres anvendelse
KR20080044836A (ko) 2005-07-15 2008-05-21 라보라뚜와르 세로노 에스. 에이. 자궁내막증 치료용 jnk 억제제
BRPI0613042A2 (pt) 2005-07-15 2010-12-14 Serono Lab inibidores de jnk para o tratamento de endometriose
CA2616479A1 (en) 2005-09-01 2007-03-08 Ares Trading S.A. Treatment of optic neuritis
US8153166B2 (en) * 2006-06-08 2012-04-10 Chih-Hsiung Lin Composition for prophylaxis or treatment of urinary system infection and method thereof
SG11201601682RA (en) 2013-09-06 2016-04-28 Aurigene Discovery Tech Ltd 1,2,4-oxadiazole derivatives as immunomodulators
AU2016230759A1 (en) * 2015-03-10 2017-09-07 Aurigene Discovery Technologies Limited 3-substituted-1,2,4-oxadiazole and thiadiazole compounds as immunomodulators
MY196130A (en) 2015-03-10 2023-03-16 Aurigene Discovery Tech Ltd 1,2,4-Oxadiazole and Thiadiazole Compounds as Immunomodulators
CN105384736B (zh) * 2015-10-28 2018-11-02 南昌大学 一种ⅳ型胶原酶抑制剂及合成方法
WO2019061324A1 (en) 2017-09-29 2019-04-04 Curis Inc. CRYSTALLINE FORMS OF IMMUNOMODULATORS
KR20200068659A (ko) 2017-10-11 2020-06-15 오리진 디스커버리 테크놀로지스 리미티드 3-치환된 1,2,4-옥사다이아졸의 결정질 형태
JP7378394B2 (ja) 2017-11-03 2023-11-13 オーリジーン オンコロジー リミテッド Tim-3およびpd-1経路の二重阻害剤
EP3706798A1 (en) 2017-11-06 2020-09-16 Aurigene Discovery Technologies Limited Conjoint therapies for immunomodulation
CN108530378B (zh) * 2018-05-29 2021-09-14 济南大学 一类含有噁二唑结构的氮原子双取代异羟肟酸类化合物、用途及其制备方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9404046D0 (en) * 1994-03-03 1994-04-20 Smithkline Beecham Corp Novel compounds
US5665753A (en) * 1994-03-03 1997-09-09 Smithkline Beecham Corporation Cytokine inhibiting imidazole substituted hydroxamic acid derivatives
US5703092A (en) 1995-04-18 1997-12-30 The Dupont Merck Pharmaceutical Company Hydroxamic acid compounds as metalloprotease and TNF inhibitors
PT946166E (pt) * 1996-12-17 2004-06-30 Warner Lambert Co Utilizacao de inibidores das metaloproteinases da matriz para tratar disturbios neurologicos e promover a cicatrizacao de feridas
CA2319493A1 (en) * 1998-03-18 1999-09-23 Regine Bohacek Heterocyclic signal transduction inhibitors, compositions containing them
JP2001031637A (ja) * 1999-05-17 2001-02-06 Fuji Chemical Industries Ltd 新規なヒドロキサム酸誘導体
GB9930570D0 (en) * 1999-12-23 2000-02-16 Pfizer Ltd Therapy
US6448278B2 (en) 1999-12-23 2002-09-10 Pfizer Inc. Procollagen C-proteinase inhibitors

Also Published As

Publication number Publication date
DE60313292D1 (de) 2007-05-31
BR0307899A (pt) 2004-12-07
ZA200406755B (en) 2006-07-26
US20110086893A1 (en) 2011-04-14
IL163413A (en) 2010-11-30
CN100351245C (zh) 2007-11-28
WO2003070711A1 (en) 2003-08-28
EP1476438A1 (en) 2004-11-17
US7358265B2 (en) 2008-04-15
AU2003205910B2 (en) 2008-12-04
NO330772B1 (no) 2011-07-11
EA200401095A1 (ru) 2005-02-24
US20050222189A1 (en) 2005-10-06
KR101098614B1 (ko) 2011-12-23
CA2475867A1 (en) 2003-08-28
UA78275C2 (en) 2007-03-15
CN1646505A (zh) 2005-07-27
JP2005522455A (ja) 2005-07-28
US20100035943A1 (en) 2010-02-11
RS51354B (sr) 2011-02-28
AU2003205910A1 (en) 2003-09-09
JP4615864B2 (ja) 2011-01-19
DE60313292T2 (de) 2007-12-27
MXPA04008132A (es) 2005-06-17
EA007609B1 (ru) 2006-12-29
GB0204159D0 (en) 2002-04-10
EP1476438B1 (en) 2007-04-18
PL210773B1 (pl) 2012-02-29
HK1078583A1 (en) 2006-03-17
NO20043846L (no) 2004-09-14
US20080227833A1 (en) 2008-09-18
CY1106730T1 (el) 2012-10-24
KR20040101232A (ko) 2004-12-02
DK1476438T3 (da) 2007-08-20
ATE360007T1 (de) 2007-05-15
CA2475867C (en) 2011-07-05
PL372268A1 (en) 2005-07-11
HRP20040725A2 (en) 2005-04-30
ES2286404T3 (es) 2007-12-01
YU71604A (sh) 2006-08-17
PT1476438E (pt) 2007-07-25

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