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AR029229A1 - SUBSTITUTED PIPERAZINE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THAT INCLUDE THEM AND THE USE OF THEM FOR THE MANUFACTURE OF A MEDICINAL PRODUCT - Google Patents

SUBSTITUTED PIPERAZINE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THAT INCLUDE THEM AND THE USE OF THEM FOR THE MANUFACTURE OF A MEDICINAL PRODUCT

Info

Publication number
AR029229A1
AR029229A1 ARP010100804A ARP010100804A AR029229A1 AR 029229 A1 AR029229 A1 AR 029229A1 AR P010100804 A ARP010100804 A AR P010100804A AR P010100804 A ARP010100804 A AR P010100804A AR 029229 A1 AR029229 A1 AR 029229A1
Authority
AR
Argentina
Prior art keywords
compounds
manufacture
pharmaceutical compositions
angina
substituted piperazine
Prior art date
Application number
ARP010100804A
Other languages
Spanish (es)
Original Assignee
Cv Therapeutics Inc
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 Cv Therapeutics Inc filed Critical Cv Therapeutics Inc
Publication of AR029229A1 publication Critical patent/AR029229A1/en

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
    • C07D295/04—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
    • C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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
    • 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
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
    • C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • 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
    • C07D295/08—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 bound oxygen or sulfur atoms
    • C07D295/084—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 bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—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 bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • 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
    • C07D317/44—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 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—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 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/54—Radicals substituted by oxygen atoms
    • 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
    • C07D317/44—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 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—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 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/58—Radicals substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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
    • C07D405/06—Heterocyclic 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 carbon chain containing only aliphatic carbon atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Neurology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pyridine Compounds (AREA)

Abstract

Compuestos de piperazina sustituidos de la formula general (1) en donde R1 a R16, R24 y X tienen los significados dados en la memoria descriptiva y sus sales de adicion de ácido farmacéuticamente aceptables, en donde los compuestos son utiles en terapia para proteger a la musculatura esquelética contra el dano como resultado del trauma o para proteger a la musculatura esquelética luego de enfermedades de la musculatura o sistémicas como ser cojera recurrente, para tratar condiciones de choque, para preservar el tejido de donante y organos utilizados en transplantes, composiciones farmacéuticas que los comprenden y el uso de dichos compuestos para la manufactura de medicamentos para el tratamiento de enfermedades cardiovasculares que incluyen arritmias atriales y ventriculares, angina Prinzmetal's (variante), angina estable, y angina inducida por el ejercicio, enfermedad cardíaca congestiva e infarto de miocardio.Substituted piperazine compounds of the general formula (1) wherein R1 to R16, R24 and X have the meanings given in the specification and their pharmaceutically acceptable acid addition salts, wherein the compounds are useful in therapy to protect the skeletal musculature against damage as a result of trauma or to protect skeletal musculature after musculature or systemic diseases such as being lame recurrent, to treat shock conditions, to preserve donor tissue and organs used in transplants, pharmaceutical compositions that they comprise and use of said compounds for the manufacture of medicaments for the treatment of cardiovascular diseases that include atrial and ventricular arrhythmias, Prinzmetal's angina (variant), stable angina, and exercise-induced angina, congestive heart disease and myocardial infarction.

ARP010100804A 2000-02-22 2001-02-22 SUBSTITUTED PIPERAZINE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THAT INCLUDE THEM AND THE USE OF THEM FOR THE MANUFACTURE OF A MEDICINAL PRODUCT AR029229A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US18418200P 2000-02-22 2000-02-22
US18430600P 2000-02-22 2000-02-22
US18445700P 2000-02-22 2000-02-22
US20639600P 2000-05-23 2000-05-23
US20926200P 2000-06-05 2000-06-05

Publications (1)

Publication Number Publication Date
AR029229A1 true AR029229A1 (en) 2003-06-18

Family

ID=27539118

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP010100804A AR029229A1 (en) 2000-02-22 2001-02-22 SUBSTITUTED PIPERAZINE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THAT INCLUDE THEM AND THE USE OF THEM FOR THE MANUFACTURE OF A MEDICINAL PRODUCT

Country Status (14)

Country Link
EP (1) EP1259493A2 (en)
JP (2) JP3980885B2 (en)
KR (1) KR100595942B1 (en)
CN (1) CN1404471A (en)
AR (1) AR029229A1 (en)
AU (2) AU3862301A (en)
BR (1) BR0108592A (en)
CA (2) CA2400176C (en)
IL (1) IL151178A0 (en)
MX (1) MXPA02008213A (en)
NO (1) NO324837B1 (en)
NZ (1) NZ520782A (en)
TW (1) TWI236471B (en)
WO (1) WO2001062744A2 (en)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2398691A1 (en) * 2000-02-18 2001-08-23 Cv Therapeutics, Inc. Partial fatty acid oxidation inhibitors in the treatment of congestive heart failure
US7001909B2 (en) 2001-07-19 2006-02-21 Cv Therapeutics, Inc. Substituted heterocyclic compounds
MXPA04000565A (en) 2001-07-19 2005-06-17 Cv Therapeutics Inc Substituted piperazine compounds and their use as fatty acid oxidation inhibitors.
ES2287574T3 (en) * 2002-12-05 2007-12-16 Cv Therapeutics, Inc. SUBSTITUTED PIPERACINE COMPOUNDS AND ITS USE AS INHIBITORS OF OXIDATION OF FATTY ACIDS.
EP1806346B1 (en) * 2002-12-05 2009-07-22 Cv Therapeutics, Inc. Substituted piperazine compounds and their use as fatty acid oxidation inhibitors
KR20050086956A (en) 2003-01-03 2005-08-30 씨브이 쎄러퓨틱스, 인코포레이티드 Substituted heterocyclic compounds
WO2005000826A1 (en) * 2003-06-23 2005-01-06 Cv Therapeutics, Inc. Urea derivatives of piperazines and piperidines as fatty acid oxidation inhibitors
CA2550257A1 (en) * 2003-12-18 2005-07-07 Cv Therapeutics, Inc. 1-akan-2-ol substituted piperazine and piperidine compounds
AU2005282492A1 (en) * 2004-09-08 2006-03-16 Gilead Palo Alto, Inc. Substituted piperazine compounds and their use as fatty acid oxidation inhibitors
CN102875490A (en) * 2012-10-19 2013-01-16 四川大学 Synthetic method used for preparing ranolazine
CN107043361B (en) * 2017-05-25 2019-07-02 合肥医工医药股份有限公司 Treat anginal compound, Preparation method and use

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4766125A (en) * 1981-06-23 1988-08-23 Janssen Pharmaceutica N.V. N-aryl-piperazinealkanamides useful for protecting hearts from myocardial injury caused by ischaemia, anoxia or hypoxia
JPS584774A (en) * 1981-06-23 1983-01-11 ジヤンセン・フア−マシユ−チカ・ナ−ムロ−ゼ・フエンノ−トシヤツプ N-aryl-piperadine alkane amides
US4567264A (en) * 1983-05-18 1986-01-28 Syntex (U.S.A.) Inc. Cardioselective aryloxy- and arylthio- hydroxypropylene-piperazinyl acetanilides which affect calcium entry
US4558129A (en) * 1983-05-18 1985-12-10 Syntex (U.S.A.) Inc. Benzodioxanyl-hydroxyethylene-piperazinyl acetanilides which effect calcium entry and β-blockade
FR2552083B1 (en) * 1983-09-15 1986-05-09 Cerm Cent Europ Rech Mauvernay (ALKYNYLOXY-3 HYDROXY-2-PROPYL) -4 PIPERAZINYL-1 N-PHENYL ACETAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
NZ247044A (en) * 1989-06-23 1997-04-24 Syntex Usa Inc Substituted For Use of ranolazine and related piperazine derivatives to treat tissue affected by muscle and neuronal damage, including transplant tissue
JPH03141258A (en) * 1989-10-25 1991-06-17 Kowa Co Novel piperazine derivative
HU209723B (en) * 1990-10-31 1994-10-28 Richter Gedeon Vegyeszet Process for producing of piperazine derivatives

Also Published As

Publication number Publication date
WO2001062744A3 (en) 2002-02-07
JP2003531116A (en) 2003-10-21
BR0108592A (en) 2004-06-29
CN1404471A (en) 2003-03-19
KR20020079893A (en) 2002-10-19
CA2657986A1 (en) 2001-08-30
AU2001238623B2 (en) 2004-09-23
NO20023954D0 (en) 2002-08-20
JP2007211009A (en) 2007-08-23
NO324837B1 (en) 2007-12-17
KR100595942B1 (en) 2006-07-03
CA2400176A1 (en) 2001-08-30
AU3862301A (en) 2001-09-03
NO20023954L (en) 2002-09-30
TWI236471B (en) 2005-07-21
IL151178A0 (en) 2003-04-10
MXPA02008213A (en) 2004-04-05
CA2400176C (en) 2009-04-28
EP1259493A2 (en) 2002-11-27
JP3980885B2 (en) 2007-09-26
WO2001062744A2 (en) 2001-08-30
NZ520782A (en) 2004-03-26

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