CO4990971A1 - Agentes terapeuticos selectivos de la mmp-3, especialmente con una buena selecti vidad con respecto a las mmp-1,2,9y/o 14 - Google Patents

Agentes terapeuticos selectivos de la mmp-3, especialmente con una buena selecti vidad con respecto a las mmp-1,2,9y/o 14

Info

Publication number
CO4990971A1
CO4990971A1 CO98077587A CO98077587A CO4990971A1 CO 4990971 A1 CO4990971 A1 CO 4990971A1 CO 98077587 A CO98077587 A CO 98077587A CO 98077587 A CO98077587 A CO 98077587A CO 4990971 A1 CO4990971 A1 CO 4990971A1
Authority
CO
Colombia
Prior art keywords
4alkyl
mmp
optionally substituted
alkyl
benzyl
Prior art date
Application number
CO98077587A
Other languages
English (en)
Inventor
Michael Jonathan Fray
Roger Rachid Dickinson
Kevin Neil Dack
Original Assignee
Pfizer
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
Priority claimed from GBGB9800510.1A external-priority patent/GB9800510D0/en
Priority claimed from GBGB9811843.3A external-priority patent/GB9811843D0/en
Application filed by Pfizer filed Critical Pfizer
Publication of CO4990971A1 publication Critical patent/CO4990971A1/es

Links

Classifications

    • 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
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61P17/02—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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • 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
    • 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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
    • C07C259/18—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings 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
    • C07D317/34—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Reproductive Health (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Pregnancy & Childbirth (AREA)
  • Endocrinology (AREA)
  • Pain & Pain Management (AREA)
  • Urology & Nephrology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Cardiology (AREA)
  • Oncology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Una sustancia que es un compuesto de fórmula (I):y sales farmacéuticamente aceptables del mismo, o un solvato de cualquier entidad, en la que R1 es H, OH, alquilo C1-4 , alcoxi C1-4 o alquenilo C2-4 , R2 es alquilo C1-6 opcionalmente sustituido con flúor, indolilo, imidazolilo, SO2 (alquilo C1-4 ), cicloalquilo C5-7 , o por un grupo OH, SH, CONH2 , CO2 H, NH2 , O NCH(=NH)NH2 opcionalmente protegido, cicloalquilo C5-7 opcionalmente sustituido con alquilo C1-6 , o es bencilo opcionalmente sustituido con OH opcionalmente protegido, alcoxi C1-6 , benciloxi o benciltio, donde los grupos protectores opcionales para dichos grupos OH, SH, CONH2 , NH2 y NHC (=NH) NH2 se seleccionan entre alquilo C1-6 , bencilo o alcanoilo C1-6 , y donde los grupos protectores opcionales para dicho CO2 H se seleccionan entre alquilo C1-6 o bencilo, cada uno de R3 , R5 y R6 se selecciona independientemente entre H y F, R4 es CH3 , Cl o F, X es HO o HONH, Y es un enlace directo u O, Z es un grupo de fórmula (a): en la que R10 es alquilo C1-4 , alcoximetilo C1-4 , hidroxi(alquilo C2-4 ), carboxi(alquilo C1-4 ) o (amino o dimetilamino)alquilo C2-4 , y R11 es fenilo, naftilo o piridilo opcionalmente sustituidos por hasta tres sustituyentes seleccionados independientemente entre halo y metilo; o (b) R14 es H, OH, CH3 o halo,...
CO98077587A 1998-01-09 1998-12-30 Agentes terapeuticos selectivos de la mmp-3, especialmente con una buena selecti vidad con respecto a las mmp-1,2,9y/o 14 CO4990971A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9800510.1A GB9800510D0 (en) 1998-01-09 1998-01-09 Therapeutic agents
GBGB9811843.3A GB9811843D0 (en) 1998-06-02 1998-06-02 Therapeutic agents

Publications (1)

Publication Number Publication Date
CO4990971A1 true CO4990971A1 (es) 2000-12-26

Family

ID=26312925

Family Applications (1)

Application Number Title Priority Date Filing Date
CO98077587A CO4990971A1 (es) 1998-01-09 1998-12-30 Agentes terapeuticos selectivos de la mmp-3, especialmente con una buena selecti vidad con respecto a las mmp-1,2,9y/o 14

Country Status (37)

Country Link
US (1) US6350907B1 (es)
EP (1) EP1047665B1 (es)
JP (1) JP3621884B2 (es)
KR (1) KR100385662B1 (es)
CN (1) CN1284942A (es)
AP (1) AP1059A (es)
AR (1) AR014270A1 (es)
AT (1) ATE252547T1 (es)
AU (1) AU736511B2 (es)
BG (1) BG104575A (es)
BR (1) BR9813719A (es)
CA (1) CA2317604C (es)
CO (1) CO4990971A1 (es)
CZ (1) CZ20002459A3 (es)
DE (1) DE69819206T2 (es)
DK (1) DK1047665T3 (es)
DZ (1) DZ2701A1 (es)
EA (1) EA002971B1 (es)
ES (1) ES2209244T3 (es)
HN (1) HN1998000199A (es)
HR (1) HRP20000460A2 (es)
HU (1) HUP0101300A3 (es)
IL (1) IL136889A0 (es)
IS (1) IS5531A (es)
MA (1) MA26594A1 (es)
NO (1) NO20003506D0 (es)
NZ (1) NZ504683A (es)
OA (1) OA11435A (es)
PA (1) PA8466101A1 (es)
PE (1) PE20000176A1 (es)
PL (1) PL342763A1 (es)
PT (1) PT1047665E (es)
SI (1) SI1047665T1 (es)
SK (1) SK10112000A3 (es)
TN (1) TNSN99002A1 (es)
TR (1) TR200001909T2 (es)
WO (1) WO1999035124A1 (es)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6352976B1 (en) 1998-12-31 2002-03-05 Aventis Pharmaceuticals Inc. Selective inhibitors of MMP-12
CA2356919A1 (en) * 1998-12-31 2000-07-13 Michael J. Janusz Selective inhibitors of mmp-12
JP2001055327A (ja) * 1999-06-11 2001-02-27 Fuji Chemical Industries Ltd 新規なヒドロキサム酸誘導体を含む医薬
US6452041B1 (en) 2000-10-16 2002-09-17 Pfizer Inc. Olefination process to itaconate and succinate derivatives
GB0025310D0 (en) * 2000-10-16 2000-11-29 Pfizer Ltd Process
PL365024A1 (en) * 2001-02-16 2004-12-27 Allelix Neuroscience, Inc. Thiophene substituted amine derivatives as glyt-1 inhibitors
GB0126389D0 (en) * 2001-11-02 2002-01-02 Pfizer Ltd Wafer
PA8578101A1 (es) * 2002-08-13 2004-05-07 Warner Lambert Co Derivados de heterobiarilo como inhibidores de metaloproteinasa de la matriz
US20040138103A1 (en) * 2002-11-07 2004-07-15 Procyte Corporation Compositions containing peptide copper complexes and metalloproteinase inhibitors and methods related thereto
AU2003300076C1 (en) 2002-12-30 2010-03-04 Angiotech International Ag Drug delivery from rapid gelling polymer composition
US7786121B2 (en) * 2003-08-23 2010-08-31 Vernalis (Oxford) Limited Derivatives of hydroxamic acid as metalloproteinase inhibitors
JP2010506147A (ja) * 2006-09-29 2010-02-25 エフ．ホフマン−ラ ロシュ アーゲー 関節リウマチを有する患者のための疾患進行のリスク評価
CN104788333B (zh) * 2015-03-19 2017-03-22 中国医科大学 2‑取代‑9,10‑蒽醌类化合物、制备方法及其用途

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US5892112A (en) 1990-11-21 1999-04-06 Glycomed Incorporated Process for preparing synthetic matrix metalloprotease inhibitors
GB9215665D0 (en) 1992-07-23 1992-09-09 British Bio Technology Compounds
US5672583A (en) 1992-11-25 1997-09-30 Merck & Co., Inc. Carboxy-peptidyl derivatives as antidegenerative active agents
US5714491A (en) 1993-04-27 1998-02-03 Celltech Therapeutics Limited Peptidyl derivatives as metalloproteinase inhibitors
GB9308695D0 (en) 1993-04-27 1993-06-09 Celltech Ltd Peptidyl derivatives
GB9320660D0 (en) 1993-10-07 1993-11-24 British Bio Technology Inhibition of cytokine production
UA48121C2 (uk) 1993-11-04 2002-08-15 Сінтекс (С.Ш.А.) Інк. Інгібітори матричних металопротеаз і фармацетична композиція на їх основі
US6037472A (en) * 1993-11-04 2000-03-14 Syntex (U.S.A.) Inc. Matrix metalloprotease inhibitors
DK0822186T3 (da) 1994-01-20 2000-06-26 British Biotech Pharm L-tert-leucin-2-pyridylamid
ATE185798T1 (de) 1994-01-22 1999-11-15 British Biotech Pharm Metalloproteinaseinhibitoren
ATE181055T1 (de) 1994-05-28 1999-06-15 British Biotech Pharm Succinyl hydroxamsäure-, n-formyl-n-hydroxy- aminocarbonsäure- und succinsäureamid-derivate und ihre verwendung als metalloprotease- inhibitoren
US5461746A (en) * 1995-01-17 1995-10-31 Tdw Delaware, Inc. Magnetic cleaning pig
US5691381A (en) 1995-04-18 1997-11-25 The Dupont Merck Pharmaceutical Company Hydroxamic and carbocyclic acids as metalloprotease inhibitors
GB9507799D0 (en) * 1995-04-18 1995-05-31 British Biotech Pharm Metalloproteinase inhibitors
JPH11504646A (ja) 1995-05-10 1999-04-27 カイロサイエンス・リミテッド 金属プロテアーゼとｔｎｆの放出を抑制するペプチド化合物およびその治療的使用
DE69627483T2 (de) 1995-05-10 2004-04-01 Darwin Discovery Ltd., Slough Peptidartige stoffe, die metalloproteinasen und die tnf-freisetzung hemmen, und ihre therapeutische verwendung
GB9513331D0 (en) 1995-06-30 1995-09-06 British Biotech Pharm Matrix metalloproteinase inhibitors
US5917090A (en) * 1995-06-30 1999-06-29 British Biotech Pharmaceuticals Ltd. Matrix metalloproteinase inhibitors
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Also Published As

Publication number Publication date
CA2317604A1 (en) 1999-07-15
HRP20000460A2 (en) 2001-06-30
NZ504683A (en) 2002-06-28
ES2209244T3 (es) 2004-06-16
SK10112000A3 (sk) 2002-02-05
AR014270A1 (es) 2001-02-07
DE69819206D1 (de) 2003-11-27
TR200001909T2 (tr) 2000-12-21
AP9901436A0 (en) 1999-03-31
EP1047665A1 (en) 2000-11-02
BG104575A (en) 2001-02-28
SI1047665T1 (en) 2004-02-29
NO20003506L (no) 2000-07-07
PA8466101A1 (es) 2000-05-24
CA2317604C (en) 2004-12-21
HUP0101300A2 (hu) 2001-08-28
JP3621884B2 (ja) 2005-02-16
OA11435A (en) 2004-04-28
EA002971B1 (ru) 2002-12-26
AP1059A (en) 2002-04-22
KR20010033990A (ko) 2001-04-25
WO1999035124A1 (en) 1999-07-15
DK1047665T3 (da) 2004-02-02
IS5531A (is) 2000-06-13
DZ2701A1 (fr) 2003-09-01
IL136889A0 (en) 2001-06-14
MA26594A1 (fr) 2004-12-20
EA200000628A1 (ru) 2001-02-26
ATE252547T1 (de) 2003-11-15
JP2002500215A (ja) 2002-01-08
HUP0101300A3 (en) 2002-11-28
AU2277699A (en) 1999-07-26
NO20003506D0 (no) 2000-07-07
EP1047665B1 (en) 2003-10-22
PL342763A1 (en) 2001-07-02
KR100385662B1 (ko) 2003-05-28
US6350907B1 (en) 2002-02-26
HN1998000199A (es) 2000-11-03
TNSN99002A1 (fr) 2005-11-10
CZ20002459A3 (cs) 2001-12-12
AU736511B2 (en) 2001-07-26
PT1047665E (pt) 2004-01-30
BR9813719A (pt) 2000-10-17
CN1284942A (zh) 2001-02-21
PE20000176A1 (es) 2000-03-10
DE69819206T2 (de) 2004-04-15

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