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ES2160525B1 - Derivados de la 4-aroilpiperidina antagonistas de los receptores ccr-3 - Google Patents

Derivados de la 4-aroilpiperidina antagonistas de los receptores ccr-3

Info

Publication number
ES2160525B1
ES2160525B1 ES009902495A ES9902495A ES2160525B1 ES 2160525 B1 ES2160525 B1 ES 2160525B1 ES 009902495 A ES009902495 A ES 009902495A ES 9902495 A ES9902495 A ES 9902495A ES 2160525 B1 ES2160525 B1 ES 2160525B1
Authority
ES
Spain
Prior art keywords
ccr
derivatives
receptors
antagonists
aroilpiperidine
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.)
Expired - Fee Related
Application number
ES009902495A
Other languages
English (en)
Other versions
ES2160525A1 (es
Inventor
Leyi Gong
Denis John Kertesz
David Bernard Smith
Robert Stephen Wilhelm
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.)
HOFFMANN LA ROCHE
F Hoffmann La Roche AG
Original Assignee
HOFFMANN LA ROCHE
F Hoffmann La Roche AG
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 HOFFMANN LA ROCHE, F Hoffmann La Roche AG filed Critical HOFFMANN LA ROCHE
Publication of ES2160525A1 publication Critical patent/ES2160525A1/es
Application granted granted Critical
Publication of ES2160525B1 publication Critical patent/ES2160525B1/es
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/08—Antiseborrheics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • 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
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Derivados de la 4-aroilpiperidina antagonistas de los receptores CCR-3 que están formados por ciertos derivados de la 4- aloilpiperidina, de fórmula (I), en donde Ar{sup,1} y Ar{sup,2} son, independientemente entre sí, arilo o heteroarilo, y R{sub,1}, R{sub,2}, X e Y se corresponden con lo descrito en las reivindicaciones y en la memoria descriptiva. La invención se refiere también a un procedimiento para la preparación de estos compuestos, a composiciones farmacéuticas que los contienen y a métodos para su empleo. Estos productos se usan para el tratamiento de enfermedades en mamíferos que responden a la administración de un antagonista del receptor CCR-3, tales como enfermedades respiratorias, por ejemplo el asma.
ES009902495A 1998-11-17 1999-11-16 Derivados de la 4-aroilpiperidina antagonistas de los receptores ccr-3 Expired - Fee Related ES2160525B1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US10879698P 1998-11-17 1998-11-17

Publications (2)

Publication Number Publication Date
ES2160525A1 ES2160525A1 (es) 2001-11-01
ES2160525B1 true ES2160525B1 (es) 2002-06-16

Family

ID=22324087

Family Applications (2)

Application Number Title Priority Date Filing Date
ES99953974T Expired - Lifetime ES2230899T3 (es) 1998-11-17 1999-11-08 Antagonistas iii receptores de 4-aroil-piperidin-ccr-3.
ES009902495A Expired - Fee Related ES2160525B1 (es) 1998-11-17 1999-11-16 Derivados de la 4-aroilpiperidina antagonistas de los receptores ccr-3

Family Applications Before (1)

Application Number Title Priority Date Filing Date
ES99953974T Expired - Lifetime ES2230899T3 (es) 1998-11-17 1999-11-08 Antagonistas iii receptores de 4-aroil-piperidin-ccr-3.

Country Status (22)

Country Link
US (1) US6140344A (es)
EP (1) EP1131291B1 (es)
JP (1) JP3475177B2 (es)
KR (1) KR20010087395A (es)
CN (1) CN1163484C (es)
AR (1) AR029150A1 (es)
AT (1) ATE280157T1 (es)
AU (1) AU757747B2 (es)
BR (1) BR9915403A (es)
CA (1) CA2350722A1 (es)
CO (1) CO5150176A1 (es)
DE (2) DE69921351T2 (es)
ES (2) ES2230899T3 (es)
FR (1) FR2785902B1 (es)
GB (1) GB2343891B (es)
IT (1) IT1307062B1 (es)
PE (1) PE20001303A1 (es)
PT (1) PT1131291E (es)
TR (1) TR200101155T2 (es)
UY (1) UY25804A1 (es)
WO (1) WO2000029377A1 (es)
ZA (1) ZA200103249B (es)

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AU2057200A (en) * 1998-12-18 2000-07-03 Du Pont Pharmaceuticals Company N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
CA2346933A1 (en) * 1998-12-18 2000-06-22 Dupont Pharmaceuticals Company N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
US6605623B1 (en) 1998-12-18 2003-08-12 Bristol-Myers Squibb Pharma Co. N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
WO2000035453A1 (en) 1998-12-18 2000-06-22 Du Pont Pharmaceuticals Company N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
SK11822001A3 (sk) 1999-03-26 2002-09-10 Astrazeneca Ab Modulátory chemokínovej aktivity, spôsoby ich prípravy, farmaceutické kompozície s ich obsahom a ich použitie v terapii
GB0013060D0 (en) 2000-05-31 2000-07-19 Astrazeneca Ab Chemical compounds
TWI227231B (en) * 2000-07-12 2005-02-01 Novartis Ag 4-benzoyl-piperidine derivatives for treating conditions mediated by CCR-3
GB0021670D0 (en) 2000-09-04 2000-10-18 Astrazeneca Ab Chemical compounds
CN1678594A (zh) 2000-09-29 2005-10-05 葛兰素集团有限公司 用于治疗炎性疾病的吗啉－乙酰胺衍生物
FR2821356A1 (fr) 2001-02-23 2002-08-30 Cerep Nouveaux derives d'arylcarbamates et d'arylurees, preparations et utilisations
GB0114699D0 (en) 2001-06-15 2001-08-08 Novartis Ag Organic compounds
GB0117899D0 (en) 2001-07-23 2001-09-12 Astrazeneca Ab Chemical compounds
SE0102809D0 (sv) * 2001-08-22 2001-08-22 Astrazeneca Ab Novel compounds
TW200303304A (en) * 2002-02-18 2003-09-01 Astrazeneca Ab Chemical compounds
AU2004215679A1 (en) * 2003-02-27 2004-09-10 F. Hoffmann-La Roche Ag CCR-3 receptor antagonists
MXPA05009771A (es) 2003-03-14 2005-10-26 Ono Pharmaceutical Co Derivados heterociclicos que contienen nitrogeno y medicamentos que los contienen como el ingrediente activo.
WO2004092169A1 (ja) 2003-04-18 2004-10-28 Ono Pharmaceutical Co., Ltd. スピロピペリジン化合物およびその医薬用途
CA2543419A1 (en) * 2003-10-24 2005-05-06 Leyi Gong Ccr3 receptor antagonists
SE0400208D0 (sv) 2004-02-02 2004-02-02 Astrazeneca Ab Chemical compounds
CN101775013A (zh) 2004-09-13 2010-07-14 小野药品工业株式会社 含氮杂环衍生物及含有其作为活性成分的药物
EP1889622A4 (en) 2005-05-31 2009-12-23 Ono Pharmaceutical Co SPIROPIPERIDINE COMPOUND AND MEDICINAL USE THEREOF
US8318931B2 (en) 2005-10-28 2012-11-27 Ono Pharmaceutical Co., Ltd. Chemokine receptor antagonists and use thereof
PT1961744E (pt) 2005-11-18 2013-05-15 Ono Pharmaceutical Co Composto que contém um grupo básico e sua utilização
EP1995246A4 (en) 2006-03-10 2010-11-17 Ono Pharmaceutical Co NITROGENATED HETEROCYCLIC DERIVATIVE AND MEDICAMENT WITH DERIVATIVE ACTIVE SUBSTANCE
WO2007132846A1 (ja) 2006-05-16 2007-11-22 Ono Pharmaceutical Co., Ltd. 保護されていてもよい酸性基を含有する化合物およびその用途
WO2008016006A1 (en) 2006-07-31 2008-02-07 Ono Pharmaceutical Co., Ltd. Compound having cyclic group bound thereto through spiro binding and use thereof
WO2010129351A1 (en) 2009-04-28 2010-11-11 Schepens Eye Research Institute Method to identify and treat age-related macular degeneration
JP5924502B2 (ja) 2011-11-28 2016-05-25 国立大学法人名古屋大学 リンパ球性漏斗下垂体後葉炎のバイオマーカー及びその用途
US11185074B2 (en) 2017-09-13 2021-11-30 Syngenta Participations Ag Microbiocidal quinoline (thio)carboxamide derivatives
WO2019053015A1 (en) * 2017-09-13 2019-03-21 Syngenta Participations Ag MICROBIOCIDE DERIVATIVES OF QUINOLINE (THIO) CARBOXAMIDE
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Also Published As

Publication number Publication date
EP1131291A1 (en) 2001-09-12
GB9926969D0 (en) 2000-01-12
ES2160525A1 (es) 2001-11-01
KR20010087395A (ko) 2001-09-15
AU757747B2 (en) 2003-03-06
ES2230899T3 (es) 2005-05-01
EP1131291B1 (en) 2004-10-20
GB2343891A (en) 2000-05-24
UY25804A1 (es) 2001-07-31
TR200101155T2 (tr) 2001-09-21
US6140344A (en) 2000-10-31
ZA200103249B (en) 2002-07-22
DE19955340A1 (de) 2000-05-31
BR9915403A (pt) 2001-08-14
ATE280157T1 (de) 2004-11-15
PE20001303A1 (es) 2000-11-30
IT1307062B1 (it) 2001-10-23
AU1045900A (en) 2000-06-05
WO2000029377A1 (en) 2000-05-25
CN1163484C (zh) 2004-08-25
FR2785902A1 (fr) 2000-05-19
DE69921351D1 (de) 2004-11-25
JP3475177B2 (ja) 2003-12-08
DE69921351T2 (de) 2006-03-09
CA2350722A1 (en) 2000-05-25
GB2343891B (en) 2001-05-30
AR029150A1 (es) 2003-06-18
CN1326441A (zh) 2001-12-12
PT1131291E (pt) 2005-01-31
ITTO990990A0 (it) 1999-11-16
FR2785902B1 (fr) 2003-09-26
ITTO990990A1 (it) 2001-05-16
JP2002529531A (ja) 2002-09-10
CO5150176A1 (es) 2002-04-29

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