HUT72448A - O-, n- ors-containing heterobicyclic compounds, pharmaceutical compositions comprising them and process for their preparation - Google Patents

O-, n- ors-containing heterobicyclic compounds, pharmaceutical compositions comprising them and process for their preparation

Info

Publication number
HUT72448A
HUT72448A HU9402443A HU9402443A HUT72448A HU T72448 A HUT72448 A HU T72448A HU 9402443 A HU9402443 A HU 9402443A HU 9402443 A HU9402443 A HU 9402443A HU T72448 A HUT72448 A HU T72448A
Authority
HU
Hungary
Prior art keywords
ors
preparation
pharmaceutical compositions
heterobicyclic compounds
containing heterobicyclic
Prior art date
Application number
HU9402443A
Other languages
English (en)
Other versions
HU9402443D0 (en
Inventor
Amedeo Leonardi
Gianni Motta
Carlo Riva
Rodolfo Testa
Original Assignee
Recordati Chem Pharm
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 ITMI920408A external-priority patent/IT1254469B/it
Application filed by Recordati Chem Pharm filed Critical Recordati Chem Pharm
Publication of HU9402443D0 publication Critical patent/HU9402443D0/hu
Publication of HUT72448A publication Critical patent/HUT72448A/hu

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/80Radicals substituted by oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D311/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D311/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D311/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/322,3-Dihydro derivatives, e.g. flavanones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D311/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/60Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D335/00Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/06Benzothiopyrans; Hydrogenated benzothiopyrans
    • 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D407/00Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Furan Compounds (AREA)
  • Pyrane Compounds (AREA)
HU9402443A 1992-02-25 1993-02-23 O-, n- ors-containing heterobicyclic compounds, pharmaceutical compositions comprising them and process for their preparation HUT72448A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI920408A IT1254469B (it) 1992-02-25 1992-02-25 Derivati benzopiranici e benzotiopiranici
US07/888,775 US5403842A (en) 1992-02-25 1992-05-26 Benzopyran and benzothiopyran derivatives

Publications (2)

Publication Number Publication Date
HU9402443D0 HU9402443D0 (en) 1994-10-28
HUT72448A true HUT72448A (en) 1996-04-29

Family

ID=26330842

Family Applications (1)

Application Number Title Priority Date Filing Date
HU9402443A HUT72448A (en) 1992-02-25 1993-02-23 O-, n- ors-containing heterobicyclic compounds, pharmaceutical compositions comprising them and process for their preparation

Country Status (25)

Country Link
EP (1) EP0558245A1 (hu)
JP (1) JPH069606A (hu)
AU (2) AU3629693A (hu)
BG (1) BG61946B1 (hu)
CA (1) CA2090156A1 (hu)
CZ (1) CZ205994A3 (hu)
DZ (1) DZ1666A1 (hu)
EE (1) EE03177B1 (hu)
EG (1) EG20333A (hu)
FI (1) FI943876A (hu)
HR (1) HRP930210A2 (hu)
HU (1) HUT72448A (hu)
IL (1) IL104824A (hu)
LT (1) LT3038B (hu)
LV (1) LV10099B (hu)
MX (1) MX9300977A (hu)
NO (1) NO943140D0 (hu)
NZ (1) NZ245995A (hu)
PL (1) PL175556B1 (hu)
SG (1) SG65570A1 (hu)
SI (1) SI9300094A (hu)
SK (1) SK280143B6 (hu)
TW (1) TW382628B (hu)
WO (1) WO1993017007A1 (hu)
ZA (1) ZA931278B (hu)

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MX9300312A (es) * 1992-01-23 1993-07-31 Pfizer Antagonistas benzopiranicos y relacionado de ltb.
FR2689127B1 (fr) * 1992-03-31 1994-05-06 Adir Cie Nouvelles 3', 5' -ditertbutyl-4'-hydroxy flavones, leur procede de preparation et les compositions pharmaceutiques les renfermant.
IT1266582B1 (it) * 1993-07-30 1997-01-09 Recordati Chem Pharm Derivati (di)azacicloesanici e diazacicloeptanici
GB9317071D0 (en) * 1993-08-17 1993-09-29 Univ Strathclyde Flavonoids
ES2159622T3 (es) * 1994-01-14 2001-10-16 Azwell Inc Derivado del diazacicloalcanoalquilsulfonamida.
FR2717175B1 (fr) * 1994-03-11 1996-06-14 Adir Nouveaux composés alkylaminoindanes, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent.
ES2101620B1 (es) * 1994-03-18 1998-04-01 Ferrer Int Nuevo compuesto derivado del cromeno.
IL112764A0 (en) * 1994-03-18 1995-05-26 Ferrer Int New chromene derivatives
US5760040A (en) * 1994-03-30 1998-06-02 Zeria Pharmaceutical Co., Ltd. Indole derivative for treating overproduction of dihydrotestosterone
US5503843A (en) * 1994-04-22 1996-04-02 Flora Inc. Transdermal delivery of alpha adrenoceptor blocking agents
DE4425146A1 (de) * 1994-07-15 1996-01-18 Basf Ag Verwendung heterocyclischer Verbindungen
GB9417135D0 (en) * 1994-08-23 1994-10-12 Medinnova S F Method
CA2188924C (en) * 1995-02-28 2008-04-08 Hirokazu Annoura Arylpiperidine and arylpiperazine derivatives and drugs containing the same
GB9507288D0 (en) * 1995-04-07 1995-05-31 Sod Conseils Rech Applic Phenoxyethylamine derivatives with high affinity for 5-HT1A receptors
US5859014A (en) * 1995-06-09 1999-01-12 Syntex (U.S.A.) Inc. Pyrimidinedione, pyrimidinetrione, triazinedione and tetrahydroquinazolinedione derivatives as α1 -adrenergic receptor antagonists
ES2157366T3 (es) * 1995-06-09 2001-08-16 Hoffmann La Roche Derivados de pirimidindiona, pirimidintriona, triacindiona como antagonistas de receptores alfa-1-adrenergicos.
JPH0967367A (ja) * 1995-06-23 1997-03-11 Suntory Ltd チオピラン誘導体
AU4153496A (en) * 1995-10-20 1997-05-07 Flora Inc. Transdermal delivery of alpha adrenoceptor blocking agents
IT1282705B1 (it) * 1996-02-28 1998-03-31 Recordati Chem Pharm Uso di antagonisti del recettore serotoninergico 5-ht|a per il trattamento dell'incontinenza urinaria
US5990114A (en) * 1996-02-28 1999-11-23 Recordati, S.A., Chemical And Pharmaceutical Company Use of 5-HT1A receptor antagonists for the treatment of urinary incontinence
JP2000506157A (ja) * 1996-03-08 2000-05-23 サンテラボ (2―アミノエチル)ベンゾフラン誘導体、その製造およびその治療的使用
FR2745815B1 (fr) * 1996-03-08 1998-06-26 Synthelabo Derives de benzofurane, leur preparations et compositions pharmaceutiques les comprenant
AU3817197A (en) * 1996-08-22 1998-03-06 Hoechst Marion Roussel, Inc. Troponyl piperazines as selective dopamine d4 receptor ligands
AU2002300904B2 (en) * 1997-05-12 2004-12-23 Ortho-Mcneil Pharmaceutical, Inc. Arylsubstituted piperazines useful in the treatment of benign prostatic hyperplasia
EP0984777B1 (en) 1997-05-12 2003-09-17 Ortho-Mcneil Pharmaceutical, Inc. Arylsubstituted piperazines useful in the treatement of benign prostatic hyperlasia
AU7455798A (en) 1997-06-04 1998-12-21 Nippon Shoji Kaisha, Ltd. Process for producing piperazinesulfonamide derivatives and salts thereof
WO1999003833A1 (en) * 1997-07-15 1999-01-28 Sankyo Company, Limited Piperazine derivatives
US6387909B1 (en) 1999-07-30 2002-05-14 Recordati S.A. Chemical And Pharmaceutical Company Thienopyranecarboxamide derivatives
US6306861B1 (en) 1999-07-30 2001-10-23 Recordati S.A. Chemical And Pharmaceutical Company Thienopyrancecarboxamide derivatives
IT1313581B1 (it) * 1999-07-30 2002-09-09 Recordati Chem Pharm Derivati tienopirancarbossamidici.
DE19941657A1 (de) * 1999-09-01 2001-03-08 Schwabe Willmar Gmbh & Co Zimtsäurenitrile, Verfahren zu ihrer Herstellung und Verwendung
US6403594B1 (en) 1999-10-18 2002-06-11 Recordati, S.A. Chemical And Pharmaceutical Company Benzopyran derivatives
IT1314192B1 (it) * 1999-10-18 2002-12-06 Recordati Chem Pharm Derivati benzopiranici
JP2002113006A (ja) 2000-10-10 2002-04-16 Toshiba Medical System Co Ltd 診断機器設定方法および診断装置
CN1150176C (zh) 2002-05-22 2004-05-19 上海医药工业研究院 芳烷酮哌嗪衍生物及其应用
US7247725B2 (en) * 2002-10-30 2007-07-24 Merck & Co., Inc. Gamma-aminoamide modulators of chemokine receptor activity
BRPI0511834A (pt) 2004-07-14 2008-01-08 Ptc Therapeutics Inc métodos por tratar hepatite c
US7781478B2 (en) 2004-07-14 2010-08-24 Ptc Therapeutics, Inc. Methods for treating hepatitis C
US7772271B2 (en) 2004-07-14 2010-08-10 Ptc Therapeutics, Inc. Methods for treating hepatitis C
US7868037B2 (en) 2004-07-14 2011-01-11 Ptc Therapeutics, Inc. Methods for treating hepatitis C
WO2006019832A1 (en) 2004-07-22 2006-02-23 Ptc Therapeutics, Inc. Thienopyridines for treating hepatitis c
BRPI0608353A2 (pt) 2005-02-17 2009-12-01 Wyeth Corp derivados de indol, benzotiofeno, benzofurano e indeno cicloalquilfundidos
CN102227417B (zh) * 2008-09-29 2015-09-16 西特里斯药业公司 作为沉默调节蛋白调节剂的色烯酮类似物
CZ304045B6 (cs) 2012-04-10 2013-09-04 Univerzita Palackého Pouzití komplexu medi obsahujících 2-fenyl-3-hydroxychinolin-4(1H)-on a deriváty 1,10-fenanthrolinu pro prípravu léciv pro lécbu nádorových onemocnení
CN108884049A (zh) 2016-02-09 2018-11-23 法玛克亚公司 喹啉酮赖氨酰氧化酶样2抑制剂及其用途
TW202031644A (zh) * 2018-11-06 2020-09-01 日商第一三共股份有限公司 苯并咪唑衍生物
CA3160428A1 (en) 2019-11-11 2021-05-20 Southwest Research Institute Recrystallized hi-6 dimethylsulfate
US11834441B2 (en) 2019-12-06 2023-12-05 Vertex Pharmaceuticals Incorporated Substituted tetrahydrofurans as modulators of sodium channels
EP4347031A1 (en) 2021-06-04 2024-04-10 Vertex Pharmaceuticals Incorporated N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamides as modulators of sodium channels
TW202334089A (zh) 2021-11-02 2023-09-01 美商夫雷爾醫療公司 Pparg反向激動劑及其用途
CN115160279B (zh) * 2022-07-27 2023-11-24 中国药科大学 苯并吡喃酮类化合物、药物组合物和应用

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GB1156973A (en) 1965-07-06 1969-07-02 Quinazoline Derivatives
DE2123923A1 (de) * 1971-05-14 1972-11-23 Boehringer Mannheim Gmbh, 6800 Mannheim 4-eckige Klammer auf omega- (Flavon-7yl-oxy) -alkyl eckige Klammer zu -pigerazin-Derivate und Verfahren zu ihrer Herstellung
NZ200981A (en) 1981-07-17 1984-10-19 Recordati Chem Pharm 3-methylflavone-8-carboxylic acid derivatives and pharmaceutical compositions
JPS60202872A (ja) * 1984-03-27 1985-10-14 Kaken Pharmaceut Co Ltd ベンゾフラン誘導体、その製法およびそれを有効成分とする降圧剤
US4678787A (en) * 1985-01-30 1987-07-07 Warner-Lambert Company 4H-1-benzopyran-4-ones and their sulfur containing analogs
JPS63139180A (ja) * 1986-12-02 1988-06-10 Tanabe Seiyaku Co Ltd カルボン酸誘導体
IL87451A0 (en) * 1987-09-04 1989-01-31 Tanabe Seiyaku Co Benzofuran derivatives,their preparation and pharmaceutical compositions containing them
US5278174A (en) * 1990-06-04 1994-01-11 Scios Nova, Inc. Sigma binding site agents

Also Published As

Publication number Publication date
AU3377393A (en) 1993-08-26
AU3629693A (en) 1993-09-13
EE03177B1 (et) 1999-04-15
LT3038B (en) 1994-09-25
JPH069606A (ja) 1994-01-18
AU660067B2 (en) 1995-06-08
MX9300977A (es) 1993-12-01
HU9402443D0 (en) 1994-10-28
IL104824A0 (en) 1993-06-10
SK100794A3 (en) 1995-04-12
ZA931278B (en) 1993-11-18
PL175556B1 (pl) 1999-01-29
EP0558245A1 (en) 1993-09-01
EG20333A (en) 1998-10-31
FI943876A0 (fi) 1994-08-23
FI943876A (fi) 1994-08-23
IL104824A (en) 1999-12-22
SG65570A1 (en) 1999-06-22
NO943140L (no) 1994-08-25
BG61946B1 (bg) 1998-10-30
HRP930210A2 (en) 1995-06-30
NZ245995A (en) 1994-09-27
NO943140D0 (no) 1994-08-25
LTIP354A (lt) 1994-04-25
DZ1666A1 (fr) 2002-02-17
SK280143B6 (sk) 1999-09-10
CA2090156A1 (en) 1993-08-26
LV10099B (en) 1995-02-20
LV10099A (lv) 1994-05-10
CZ205994A3 (en) 1995-02-15
WO1993017007A1 (en) 1993-09-02
BG98990A (bg) 1995-05-31
SI9300094A (en) 1993-09-30
TW382628B (en) 2000-02-21

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Legal Events

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DFD9 Temporary protection cancelled due to non-payment of fee