PL361382A1 - O-podstawione pochodne 6-metylotramadolu - Google Patents

O-podstawione pochodne 6-metylotramadolu

Info

Publication number
PL361382A1
PL361382A1 PL01361382A PL36138201A PL361382A1 PL 361382 A1 PL361382 A1 PL 361382A1 PL 01361382 A PL01361382 A PL 01361382A PL 36138201 A PL36138201 A PL 36138201A PL 361382 A1 PL361382 A1 PL 361382A1
Authority
PL
Poland
Prior art keywords
substituted
methyl
tramadol derivatives
tramadol
derivatives
Prior art date
Application number
PL01361382A
Other languages
English (en)
Inventor
Helmut Buschmann
Babette-Yvonne Kögel
Elmar Friderichs
Dagmar Kaulartz
Original Assignee
Grünenthal GmbH
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=7658871&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PL361382(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Grünenthal GmbH filed Critical Grünenthal GmbH
Publication of PL361382A1 publication Critical patent/PL361382A1/pl

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
    • 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
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • 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
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/42—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • 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
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/32—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
PL01361382A 2000-09-29 2001-09-28 O-podstawione pochodne 6-metylotramadolu PL361382A1 (pl)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10049483A DE10049483A1 (de) 2000-09-29 2000-09-29 Substituierte 1-Aminobutan-3-ol-Derivate
PCT/EP2001/011276 WO2002026694A1 (de) 2000-09-29 2001-09-28 O-substituierte 6-methyl-tramadol-derivate

Publications (1)

Publication Number Publication Date
PL361382A1 true PL361382A1 (pl) 2004-10-04

Family

ID=7658871

Family Applications (2)

Application Number Title Priority Date Filing Date
PL01361382A PL361382A1 (pl) 2000-09-29 2001-09-28 O-podstawione pochodne 6-metylotramadolu
PL01361632A PL361632A1 (pl) 2000-09-29 2001-09-28 Podstawione pochodne 1-aminobutan-3-olu

Family Applications After (1)

Application Number Title Priority Date Filing Date
PL01361632A PL361632A1 (pl) 2000-09-29 2001-09-28 Podstawione pochodne 1-aminobutan-3-olu

Country Status (29)

Country Link
US (2) US7022739B2 (pl)
EP (2) EP1322592B2 (pl)
JP (2) JP2004510755A (pl)
KR (2) KR100864796B1 (pl)
CN (2) CN1478067A (pl)
AR (1) AR034158A1 (pl)
AT (2) ATE272046T1 (pl)
AU (4) AU2057802A (pl)
BR (2) BR0114381A (pl)
CA (2) CA2423860A1 (pl)
DE (3) DE10049483A1 (pl)
DK (2) DK1322592T4 (pl)
EC (2) ECSP034532A (pl)
ES (2) ES2225628T3 (pl)
HK (2) HK1052924B (pl)
HU (2) HUP0303361A3 (pl)
IL (2) IL155105A0 (pl)
MX (2) MXPA03002738A (pl)
NO (2) NO20031387L (pl)
NZ (2) NZ524976A (pl)
PE (1) PE20020413A1 (pl)
PL (2) PL361382A1 (pl)
PT (2) PT1322592E (pl)
RU (2) RU2288219C2 (pl)
SI (2) SI1322593T1 (pl)
SK (2) SK286727B6 (pl)
TR (2) TR200402030T4 (pl)
WO (2) WO2002026694A1 (pl)
ZA (2) ZA200303214B (pl)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10049483A1 (de) * 2000-09-29 2002-05-02 Gruenenthal Gmbh Substituierte 1-Aminobutan-3-ol-Derivate
ES2268095T3 (es) 2001-10-16 2007-03-16 Endo Pharmaceuticals Inc. Uso de carbinoles para el tratamiento de la disfuncion neuropatica.
CA2473461C (en) * 2002-01-11 2011-11-01 Sankyo Company, Limited Amino alcohol derivative or phosphonic acid derivative and medicinal composition containing these
US20050182056A9 (en) * 2002-02-21 2005-08-18 Seth Pawan Modified release formulations of at least one form of tramadol
US8128957B1 (en) 2002-02-21 2012-03-06 Valeant International (Barbados) Srl Modified release compositions of at least one form of tramadol
EP1685829B1 (de) 2002-11-22 2008-04-09 Grünenthal GmbH Verwendung von (1RS,3RS,6RS)-6-dimethylaminomethyl-1-(3-methoxy-phenyl)-cyclohexan-1,3-diol zur Behandlung von Entzündungsschmerz
BRPI0507944A (pt) 2004-02-24 2007-07-24 Sankyo Co composição farmacêutica
MX2009012685A (es) * 2007-05-31 2009-12-14 Sepracor Inc Cicloalquilaminas sustituidas con fenilo como inhibidores de la reabsorcion de monoamina.
JP2012511021A (ja) * 2008-12-05 2012-05-17 アークル インコーポレイテッド Ｒａｆの阻害剤およびその使用
ES2343050B1 (es) * 2008-12-16 2011-06-14 Chemo Iberica, S.A. Procedimiento para la preparacion de desvenlafaxina y sus sales de adicion de acido farmaceuticamente aceptables.
WO2012100423A1 (en) 2011-01-27 2012-08-02 Eli Lilly And Company Analgesic compounds, methods, and formulations
WO2017125351A1 (en) * 2016-01-21 2017-07-27 Laboratorios Lesvi Sl Process for preparing (( r)-3-[(-1-methylpyrrolidin-2-yl)methyl]-5-(2-phenylsulfonylethyl)-1h-indole

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3652589A (en) * 1967-07-27 1972-03-28 Gruenenthal Chemie 1-(m-substituted phenyl)-2-aminomethyl cyclohexanols
ZA732238B (en) * 1972-04-06 1974-01-30 American Home Prod Benzylamine analgesics
US4155935A (en) 1973-03-26 1979-05-22 American Home Products Corporation Benzylamine analgesics
DE19525137C2 (de) * 1995-07-11 2003-02-27 Gruenenthal Gmbh 6-Dimethylaminomethyl-1-phenyl-cyclohexanverbin -dungen als Zwischenprodukte zur Herstellung pharmazeutischer Wirkstoffe
US6017963A (en) * 1995-11-14 2000-01-25 Euro-Celtique, S.A. Formulation for intranasal administration
DE19547766A1 (de) * 1995-12-20 1997-06-26 Gruenenthal Gmbh 1-Phenyl-2-dimethylaminomethyl-cyclohexan-1-ol-verbindungen als pharmazeutische Wirkstoffe
DE19601744C2 (de) 1996-01-19 1998-04-16 Gruenenthal Gmbh Verfahren zur Herstellung der Enantiomeren von O-Demethyltramadol
DE19609847A1 (de) * 1996-03-13 1997-09-18 Gruenenthal Gmbh Dimethyl-(3-aryl-but-3-enyl)-aminverbindungen als pharmazeutische Wirkstoffe
US5919826A (en) * 1996-10-24 1999-07-06 Algos Pharmaceutical Corporation Method of alleviating pain
US6245804B1 (en) * 1997-05-30 2001-06-12 Schering Aktiengesellschaft Nonsteroidal gestagens
CN1151122C (zh) * 1997-07-15 2004-05-26 拉辛斯基有限公司 反胺苯环醇及其盐以及它们的制备方法
DK1077923T3 (da) * 1998-05-22 2004-04-13 Mallinckrodt Inc Forbedret syntese og rensning af (R*,R*)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol-hydrochlorid
ES2141688B1 (es) * 1998-11-06 2001-02-01 Vita Invest Sa Nuevos esteres derivados de compuestos fenil-ciclohexil sustituidos.
DE19915601A1 (de) * 1999-04-07 2000-10-19 Gruenenthal Gmbh 3-Amino-3-arylpropan-1-ol-Derivate, deren Herstellung und Verwendung
ES2234651T3 (es) * 1999-08-20 2005-07-01 Ortho-Mcneil Pharmaceutical, Inc. Composicion que comprende una materia de tramadol y un farmaco anticonvulsivo.
PE20010623A1 (es) * 1999-10-05 2001-07-07 Gruenenthal Chemie Uso de (+)-tramadol y/o o-demetiltramadol para tratamiento de urgencia urinaria incrementada y/o incontinencia urinaria
US6339105B1 (en) * 1999-10-12 2002-01-15 Ortho-Mcneil Pharmaceutical, Inc. Analgesic regimen
DE10000312A1 (de) * 2000-01-05 2001-07-12 Gruenenthal Gmbh Substituierte Aminomethyl-Phenyl-Cyclohexanderivate
DE10049483A1 (de) * 2000-09-29 2002-05-02 Gruenenthal Gmbh Substituierte 1-Aminobutan-3-ol-Derivate
DE10048714A1 (de) * 2000-09-30 2002-04-11 Gruenenthal Gmbh 5-Amino-1-penlen-3-ol-Derivate
US6649783B2 (en) * 2001-10-03 2003-11-18 Euro-Celtique, S.A. Synthesis of (+/-)-2-((dimethylamino)methyl)-1-(aryl)cyclohexanols
AU2002364517A1 (en) * 2001-11-30 2003-06-17 Sepracor Inc. Tramadol analogs and uses thereof

Also Published As

Publication number Publication date
EP1322592B2 (de) 2009-06-17
MXPA03002738A (es) 2004-01-26
US6828345B2 (en) 2004-12-07
ATE272045T1 (de) 2004-08-15
KR20030059160A (ko) 2003-07-07
EP1322593A1 (de) 2003-07-02
EP1322593B1 (de) 2004-07-28
CN1466567A (zh) 2004-01-07
NZ524976A (en) 2005-01-28
BR0114380A (pt) 2003-12-30
CA2423903A1 (en) 2003-03-27
SK286727B6 (sk) 2009-04-06
DE50103036D1 (de) 2004-09-02
AR034158A1 (es) 2004-02-04
IL155106A0 (en) 2003-10-31
KR20030077531A (ko) 2003-10-01
JP2004509939A (ja) 2004-04-02
ECSP034530A (es) 2003-05-26
DK1322592T4 (da) 2009-10-12
AU8993701A (en) 2002-04-15
US7022739B2 (en) 2006-04-04
US20030220389A1 (en) 2003-11-27
SI1322592T1 (en) 2005-02-28
NZ525171A (en) 2006-02-24
US20030216393A1 (en) 2003-11-20
TR200402030T4 (tr) 2004-09-21
CA2423860A1 (en) 2003-03-27
DE10049483A1 (de) 2002-05-02
WO2002026694A1 (de) 2002-04-04
SI1322593T1 (en) 2004-12-31
DE50103035D1 (de) 2004-09-02
DK1322592T3 (da) 2004-11-22
ECSP034532A (es) 2003-05-26
RU2286334C2 (ru) 2006-10-27
HK1052924A1 (en) 2003-10-03
ES2225628T3 (es) 2005-03-16
ES2225605T3 (es) 2005-03-16
NO20031387L (no) 2003-05-21
TR200402230T4 (tr) 2004-10-21
PT1322592E (pt) 2004-12-31
KR100864796B1 (ko) 2008-10-23
CN100391933C (zh) 2008-06-04
HK1052925B (zh) 2005-04-01
HUP0303195A2 (hu) 2003-12-29
DK1322593T3 (da) 2004-10-11
MXPA03002737A (es) 2004-01-26
BR0114381A (pt) 2003-12-30
HUP0303361A3 (en) 2007-03-28
HK1052924B (zh) 2005-03-24
EP1322592A1 (de) 2003-07-02
AU2001289937B2 (en) 2007-01-18
HUP0303195A3 (en) 2007-03-28
SK3382003A3 (en) 2003-08-05
AU2057802A (en) 2002-04-08
IL155105A0 (en) 2003-10-31
ZA200303214B (en) 2004-08-31
SK3402003A3 (en) 2003-09-11
JP2004510755A (ja) 2004-04-08
PT1322593E (pt) 2004-12-31
CN1478067A (zh) 2004-02-25
AU2002220578B2 (en) 2006-11-30
HUP0303361A2 (hu) 2004-03-01
NO20031387D0 (no) 2003-03-26
WO2002028817A1 (de) 2002-04-11
NO20031382L (no) 2003-05-16
PL361632A1 (pl) 2004-10-04
ATE272046T1 (de) 2004-08-15
HK1052925A1 (en) 2003-10-03
NO20031382D0 (no) 2003-03-26
ZA200303220B (en) 2004-08-19
KR100835549B1 (ko) 2008-06-09
RU2288219C2 (ru) 2006-11-27
EP1322592B1 (de) 2004-07-28
PE20020413A1 (es) 2002-05-18
ES2225605T5 (es) 2009-11-18

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Legal Events

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DISC Decisions on discontinuance of the proceedings (taken after the publication of the particulars of the applications)