MXPA03002309A - Guaniduros de acido cinamico sustituidos, metodo para su preparacion, su uso como farmaco, y farmaco que contiene dichos compuestos. - Google Patents

Guaniduros de acido cinamico sustituidos, metodo para su preparacion, su uso como farmaco, y farmaco que contiene dichos compuestos.

Info

Publication number
MXPA03002309A
MXPA03002309A MXPA03002309A MXPA03002309A MXPA03002309A MX PA03002309 A MXPA03002309 A MX PA03002309A MX PA03002309 A MXPA03002309 A MX PA03002309A MX PA03002309 A MXPA03002309 A MX PA03002309A MX PA03002309 A MXPA03002309 A MX PA03002309A
Authority
MX
Mexico
Prior art keywords
medicament
compounds
production
cinnamic acid
substituted cinnamic
Prior art date
Application number
MXPA03002309A
Other languages
English (en)
Inventor
Uwe Heinelt
Original Assignee
Aventis Pharma 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
Application filed by Aventis Pharma Gmbh filed Critical Aventis Pharma Gmbh
Publication of MXPA03002309A publication Critical patent/MXPA03002309A/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • C07D295/26—Sulfur atoms
    • 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
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
    • C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
    • C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
    • C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/41—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/52—Y being a hetero atom
    • C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
    • C07C311/57—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/58—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings having nitrogen atoms of the sulfonylurea groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 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
    • C07D207/14—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrrole Compounds (AREA)
MXPA03002309A 2000-09-22 2001-09-08 Guaniduros de acido cinamico sustituidos, metodo para su preparacion, su uso como farmaco, y farmaco que contiene dichos compuestos. MXPA03002309A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10046993A DE10046993A1 (de) 2000-09-22 2000-09-22 Substituierte Zimtsäureguanidide, Verfahren zur ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltendes Medikament
PCT/EP2001/010375 WO2002024637A1 (de) 2000-09-22 2001-09-08 Substituierte zimtsäureguanidide, verfahren zu ihrer herstellung, ihre verwendung als medikament sowie sie enthaltendes medikament

Publications (1)

Publication Number Publication Date
MXPA03002309A true MXPA03002309A (es) 2003-06-06

Family

ID=7657232

Family Applications (1)

Application Number Title Priority Date Filing Date
MXPA03002309A MXPA03002309A (es) 2000-09-22 2001-09-08 Guaniduros de acido cinamico sustituidos, metodo para su preparacion, su uso como farmaco, y farmaco que contiene dichos compuestos.

Country Status (21)

Country Link
US (1) US6399824B1 (es)
EP (1) EP1322602A1 (es)
JP (1) JP2004509163A (es)
KR (1) KR20030094210A (es)
CN (1) CN1462268A (es)
AR (1) AR030947A1 (es)
AU (1) AU2001293802A1 (es)
BR (1) BR0114092A (es)
CA (1) CA2422709A1 (es)
CZ (1) CZ2003815A3 (es)
DE (1) DE10046993A1 (es)
EE (1) EE200300110A (es)
HU (1) HUP0303699A3 (es)
IL (1) IL154953A0 (es)
MX (1) MXPA03002309A (es)
NO (1) NO20031273L (es)
PL (1) PL360993A1 (es)
RU (1) RU2003111462A (es)
SK (1) SK3542003A3 (es)
WO (1) WO2002024637A1 (es)
ZA (1) ZA200301778B (es)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2271574T3 (es) 2002-04-15 2007-04-16 Janssen Pharmaceutica N.V. Derivados triciclicos de quinazolina inhibidores de la farnesiltransferasa, sustituidos con imidazoles o triazoles enlazados al carbono.
FR2840302B1 (fr) * 2002-06-03 2004-07-16 Aventis Pharma Sa Derives d'isoindolones, procede de preparation et intermediaire de ce procede a titre de medicaments et compositions pharmaceutiques les renfermant
PE20060459A1 (es) * 2004-06-16 2006-05-30 Wyeth Corp DERIVADOS DE AMINO-5,5-DIFENILIMIDAZOLONA COMO INHIBIDORES DE LA ß-SECRETASA
AU2005264917A1 (en) * 2004-06-16 2006-01-26 Wyeth Diphenylimidazopyrimidine and -imidazole amines as inhibitors of B-secretase
CN101103034A (zh) * 2005-01-14 2008-01-09 惠氏公司 抑制β-分泌酶的氨基-咪唑酮
WO2006083760A1 (en) * 2005-02-01 2006-08-10 Wyeth AMINO-PYRIDINES AS INHIBITORS OF β-SECRETASE
CN101146769A (zh) * 2005-02-14 2008-03-19 惠氏公司 作为β-分泌酶抑制剂的唑基酰基胍
WO2006088705A1 (en) * 2005-02-14 2006-08-24 Wyeth Terphenyl guanidines as [beta symbol] -secretase inhibitors
TW200738683A (en) * 2005-06-30 2007-10-16 Wyeth Corp Amino-5-(5-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation
WO2007005404A1 (en) * 2005-06-30 2007-01-11 Wyeth AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION
TW200730523A (en) * 2005-07-29 2007-08-16 Wyeth Corp Cycloalkyl amino-hydantoin compounds and use thereof for β-secretase modulation
EP2256107A1 (en) * 2005-09-26 2010-12-01 Wyeth LLC Amino-5-[4-(difluoromethoxy)phenyl]-5-phenylimidazolone compounds as inhibitors of the beta-secretase (BACE)
CN101360737A (zh) * 2005-12-19 2009-02-04 惠氏公司 2-氨基-5-哌啶咪唑酮化合物和其用于β分泌酶调节的用途
WO2007100536A1 (en) * 2006-02-24 2007-09-07 Wyeth DIHYDROSPIRO[DIBENZO[A,D][7]ANNULENE-5,4'-IMIDAZOL] COMPOUNDS FOR THE INHIBITION OF β-SECRETASE
US7700606B2 (en) * 2006-08-17 2010-04-20 Wyeth Llc Imidazole amines as inhibitors of β-secretase
JP2010504326A (ja) * 2006-09-21 2010-02-12 ワイス エルエルシー β−セクレターゼを阻害するためのインドリルアルキルピリジン−２−アミン
PE20090160A1 (es) * 2007-03-20 2009-02-11 Wyeth Corp COMPUESTOS AMINO-5-[4-(DIFLUOROMETOXI)FENIL SUSTITUIDO]-5-FENILIMIDAZOLONA COMO INHIBIDORES DE ß-SECRETASA
PE20090617A1 (es) * 2007-03-23 2009-05-08 Wyeth Corp Compuestos amino-5-[-4-(difluorometoxi)fenil]-5-fenilimidazolona para la inhibicion de -secretasa
WO2018129556A1 (en) 2017-01-09 2018-07-12 Ardelyx, Inc. Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
MX345283B (es) 2008-12-31 2017-01-24 Ardelyx Inc Compuestos y metodos para inhibir el antiporte mediado por intercambiador de iones de sodio/iones de hidrogeno (nhe) en el tratamiento de trastornos asociados con retencion de fluido o sobrecarga de sal y trastornos del tracto gastrointestinal.
US20100119499A1 (en) * 2009-09-17 2010-05-13 Kneller Bruce W Stilbene-based compositions and methods of use therefor
US20120088737A2 (en) * 2009-10-02 2012-04-12 Ajinomoto Co., Inc Novel acyl guanidine derivatives
MX366293B (es) 2012-08-21 2019-07-04 Ardelyx Inc Compuestos y metodos para inhibir al antipuerto mediado por nhe en el tratamiento de trastornos asociados con la retencion de fluidos o la sobrecarga de sal y trastornos del tracto gastrointestinal.
US10376481B2 (en) 2012-08-21 2019-08-13 Ardelyx, Inc. Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
JP6377132B2 (ja) 2013-04-12 2018-08-22 アーデリクス，インコーポレーテッド Ｎｈｅ３結合化合物およびリン酸輸送の阻害方法
EP3565808A1 (en) 2017-01-09 2019-11-13 Ardelyx, Inc. Compounds useful for treating gastrointestinal tract disorders
EA201991676A1 (ru) 2017-01-09 2020-01-30 Арделикс, Инк. Ингибиторы nhe-опосредованного антипорта
AU2018335130B2 (en) 2017-08-04 2023-02-16 Ardelyx, Inc. Glycyrrhetinic acid derivatives for treating hyperkalemia
EP3921327B1 (en) 2019-02-07 2023-04-05 Ardelyx, Inc. Glycyrrhetinic acid derivatives for use in treating hyperkalemia
US20200368223A1 (en) 2019-05-21 2020-11-26 Ardelyx, Inc. Methods for inhibiting phosphate transport

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0723956B1 (de) * 1995-01-30 1999-10-13 Hoechst Aktiengesellschaft Basisch-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
DE19502795A1 (de) * 1995-01-30 1996-08-01 Hoechst Ag Benzolsulfonamid-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
US6057322A (en) 1995-01-30 2000-05-02 Hoechst Aktiengesellschaft Basically-substituted benzoylguanidines, a process for preparing them, their use as a medicament or diagnostic agent, and a medicament containing them
DE19518796A1 (de) 1995-05-22 1996-11-28 Hoechst Ag Fluorphenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
DE19527305A1 (de) 1995-07-26 1997-01-30 Hoechst Ag Substituierte Zimtsäureguanidide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
DE19633966A1 (de) * 1996-08-22 1998-02-26 Hoechst Ag Phenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament

Also Published As

Publication number Publication date
WO2002024637A1 (de) 2002-03-28
CZ2003815A3 (cs) 2003-06-18
EE200300110A (et) 2005-04-15
IL154953A0 (en) 2003-10-31
BR0114092A (pt) 2003-09-09
HUP0303699A2 (hu) 2004-04-28
RU2003111462A (ru) 2004-11-10
US6399824B1 (en) 2002-06-04
KR20030094210A (ko) 2003-12-11
NO20031273D0 (no) 2003-03-19
US20020058710A1 (en) 2002-05-16
HUP0303699A3 (en) 2006-02-28
NO20031273L (no) 2003-05-14
JP2004509163A (ja) 2004-03-25
PL360993A1 (en) 2004-09-20
AR030947A1 (es) 2003-09-03
SK3542003A3 (en) 2003-09-11
ZA200301778B (en) 2004-04-16
CN1462268A (zh) 2003-12-17
DE10046993A1 (de) 2002-04-11
EP1322602A1 (de) 2003-07-02
AU2001293802A1 (en) 2002-04-02
CA2422709A1 (en) 2003-03-18

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