DE69331171T2 - Chinolin und Chinazolin Derivate zur Behandlung von Arthritis - Google Patents

Chinolin und Chinazolin Derivate zur Behandlung von Arthritis

Info

Publication number
DE69331171T2
DE69331171T2 DE69331171T DE69331171T DE69331171T2 DE 69331171 T2 DE69331171 T2 DE 69331171T2 DE 69331171 T DE69331171 T DE 69331171T DE 69331171 T DE69331171 T DE 69331171T DE 69331171 T2 DE69331171 T2 DE 69331171T2
Authority
DE
Germany
Prior art keywords
group
ring
alkyl
substituted
quinoline
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
DE69331171T
Other languages
German (de)
English (en)
Other versions
DE69331171D1 (de
Inventor
Atsuo Baba
Haruhiko Makino
Takashi Sohda
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.)
Takeda Pharmaceutical Co Ltd
Original Assignee
Takeda Chemical Industries 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 Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd
Application granted granted Critical
Publication of DE69331171D1 publication Critical patent/DE69331171D1/de
Publication of DE69331171T2 publication Critical patent/DE69331171T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/74Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
    • C07D239/76N-oxides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/47Quinolines; Isoquinolines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61P25/00Drugs for disorders of the nervous system
    • 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]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic 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
    • C07D215/16Heterocyclic 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
    • C07D215/48Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/74Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/14Heterocyclic 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 three or more hetero rings
    • 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
    • C07D413/10Heterocyclic 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 aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
DE69331171T 1992-04-24 1993-04-22 Chinolin und Chinazolin Derivate zur Behandlung von Arthritis Expired - Fee Related DE69331171T2 (de)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP10642492 1992-04-24
JP12188792 1992-05-14
JP28586592 1992-10-23
JP3795293 1993-02-26

Publications (2)

Publication Number Publication Date
DE69331171D1 DE69331171D1 (de) 2002-01-03
DE69331171T2 true DE69331171T2 (de) 2002-07-11

Family

ID=27460501

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69331171T Expired - Fee Related DE69331171T2 (de) 1992-04-24 1993-04-22 Chinolin und Chinazolin Derivate zur Behandlung von Arthritis

Country Status (14)

Country Link
US (1) US5948782A (enExample)
EP (1) EP0567107B1 (enExample)
KR (1) KR940005273A (enExample)
CN (1) CN1079222A (enExample)
AT (1) ATE209199T1 (enExample)
AU (1) AU656069B2 (enExample)
CA (1) CA2094774A1 (enExample)
DE (1) DE69331171T2 (enExample)
FI (1) FI931855A7 (enExample)
HU (2) HUT64322A (enExample)
NO (1) NO305973B1 (enExample)
NZ (1) NZ247477A (enExample)
RU (1) RU2130934C1 (enExample)
TW (1) TW232013B (enExample)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5455253A (en) * 1992-10-20 1995-10-03 Zeneca Limited Heterocyclic derivatives
KR100224135B1 (ko) * 1993-01-28 1999-10-15 다께다 구니오 퀴놀린 또는 퀴나졸린 유도체, 그 제조 및 용도
EP0625522B1 (en) * 1993-05-18 1998-08-19 Takeda Chemical Industries, Ltd. Benzopyran derivatives and their use
DE69422450T2 (de) * 1993-06-29 2000-06-08 Takeda Chemical Industries, Ltd. Chinoline oder Chinazolin-Derivate und deren Verwendung zur Herstellung eines Medikaments für die Behandlung von Osteoporose
CN1046270C (zh) * 1993-11-12 1999-11-10 法玛西雅厄普约翰美国公司 嘧啶-硫烷基或烷基醚化合物
AU1860995A (en) * 1994-03-08 1995-09-25 Takeda Chemical Industries Ltd. Quinoline or quinazoline derivatives as anti-inflammatory agents, in particular for treating arthritis
US5641788A (en) 1994-06-07 1997-06-24 Takeda Chemical Industries, Ltd. Quinoline derivatives and pharmaceutical composition containing them
HUP9801628A2 (hu) * 1995-04-28 1999-01-28 Takeda Chemical Industries, Ltd. Artritisz elleni gyógyászati készítmények
BR9610314A (pt) * 1995-09-13 1999-07-06 Takeda Chemical Industries Ltd Imunossupressor processos para prevenir ou tratar doenças autoimunes em mamíferos e prevenir rejeição de enxerto uso de um composto composição farmacêutica e uso da mesma
JP2002505288A (ja) 1998-03-02 2002-02-19 コセンシス,インコーポレイテッド 置換キナゾリンおよびアナログならびにそれらの使用
US6184226B1 (en) 1998-08-28 2001-02-06 Scios Inc. Quinazoline derivatives as inhibitors of P-38 α
WO2001042218A1 (en) * 1999-12-13 2001-06-14 Kabushiki Kaisha Toyota Chuo Kenkyusho Quinoline derivatives and organic electroluminescent devices
AR038658A1 (es) 2001-06-15 2005-01-26 Novartis Ag Derivados de 4-aril-2(1h) quinazolinona y 4-aril-quinazolina 2-sustituidas, un proceso para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la preparacion de un medicamento
US6620939B2 (en) 2001-09-18 2003-09-16 General Electric Company Method for producing bisphenol catalysts and bisphenols
CN100551532C (zh) * 2003-03-03 2009-10-21 沙伯基础创新塑料知识产权有限公司 制备双酚催化剂和双酚的方法
AU2005257483B2 (en) * 2004-06-25 2011-02-03 Sumitomo Chemical Company, Limited Method for producing (Z)-1-phenyl-1-diethylaminocarbonyl-2-hydroxymethyl cyclopropane
TW201111362A (en) 2009-06-25 2011-04-01 Amgen Inc Heterocyclic compounds and their uses
KR20130095772A (ko) 2010-10-05 2013-08-28 퍼듀 퍼머 엘피 나트륨 채널 차단제로서 퀴나졸린 화합물
US8765768B2 (en) * 2010-11-17 2014-07-01 Amgen Inc. Heterocyclic compounds and their uses
BR112015002950A2 (pt) * 2012-08-24 2017-08-08 Hoffmann La Roche novos derivados de bicíclico-piridina
US9815797B2 (en) 2013-12-09 2017-11-14 Ucb Biopharma Sprl Fused bicyclic heteroaromatic derivatives as modulators of TNF activity

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2134169A1 (en) * 1971-04-23 1972-12-08 Clin Byla Ets 3-acyl-4-substd - quinoline derivs - analgesics, antiinflammatories, diuretics
JPS5671074A (en) * 1979-11-12 1981-06-13 Takeda Chem Ind Ltd 1,2-disubstituted-4-halogenoimidazole-5-acetic acid derivative
JPS6165869A (ja) * 1984-09-07 1986-04-04 Kyowa Hakko Kogyo Co Ltd キノリン−n−オキシド誘導体
NO174506B (no) * 1984-10-30 1994-02-07 Usv Pharma Corp Analogifremgangsmaate ved fremstilling av terapeutisk aktive forbindelser
ES2028834T3 (es) * 1986-09-12 1992-07-16 American Cyanamid Company Metodo para la preparacion de accidos piridin-2,3-dicarboxilico.
GB8716971D0 (en) * 1987-07-17 1987-08-26 Pfizer Ltd Therapeutic agents
CA1336714C (en) * 1987-08-20 1995-08-15 Yoshihiro Fujikawa Quinoline type mevalonolactone inhibitors of cholesterol biosynthesis
US4968701A (en) * 1988-04-26 1990-11-06 E. I. Du Pont De Nemours And Company 4-Quinoline carboxylic acid derivatives useful as immunosuppressive agents
IE892088L (en) * 1988-07-12 1990-01-12 William Henry Deryk Morris Quinoline derivatives, their production and use
US4968702A (en) * 1989-01-17 1990-11-06 American Cyanamid Company Substituted quinolinecarboxylic acids
US5124325A (en) * 1989-06-13 1992-06-23 Kyorin Pharmaceutical Co., Ltd. Therapeutic agents of metabolic bone disease
DE3935491A1 (de) * 1989-10-25 1991-05-02 Bayer Ag Substituierte (chinolin-2-yl-methoxy)phenyl-carbonylharnstoffe
EP0524974A1 (de) * 1990-04-10 1993-02-03 Byk Gulden Lomberg Chemische Fabrik Gmbh Pyridine als arzneimittel
DE4105551A1 (de) * 1991-02-22 1992-08-27 Bayer Ag 2-substituierte chinoline, verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln
DE4129500A1 (de) * 1991-09-05 1993-03-11 Basf Ag Hochschlagzaehe, flammgeschuetzte polyphenylenether/polyamidformmassen
KR100224135B1 (ko) * 1993-01-28 1999-10-15 다께다 구니오 퀴놀린 또는 퀴나졸린 유도체, 그 제조 및 용도

Also Published As

Publication number Publication date
EP0567107A1 (en) 1993-10-27
AU3699193A (en) 1993-10-28
HU211852A9 (en) 1995-12-28
HUT64322A (en) 1993-12-28
US5948782A (en) 1999-09-07
RU2130934C1 (ru) 1999-05-27
FI931855L (fi) 1993-10-25
NO931482L (no) 1993-10-25
ATE209199T1 (de) 2001-12-15
DE69331171D1 (de) 2002-01-03
CA2094774A1 (en) 1993-10-25
AU656069B2 (en) 1995-01-19
CN1079222A (zh) 1993-12-08
EP0567107B1 (en) 2001-11-21
NO305973B1 (no) 1999-08-30
NO931482D0 (no) 1993-04-22
KR940005273A (ko) 1994-03-21
FI931855A0 (fi) 1993-04-23
NZ247477A (en) 1995-07-26
TW232013B (enExample) 1994-10-11
HU9301197D0 (en) 1993-07-28
FI931855A7 (fi) 1993-10-25

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