RU2003125647A - Способ синтеза авторвастатина и промежуточный фенилборонат (вараинты) - Google Patents

Способ синтеза авторвастатина и промежуточный фенилборонат (вараинты) Download PDF

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RU2003125647A
RU2003125647A RU2003125647/04A RU2003125647A RU2003125647A RU 2003125647 A RU2003125647 A RU 2003125647A RU 2003125647/04 A RU2003125647/04 A RU 2003125647/04A RU 2003125647 A RU2003125647 A RU 2003125647A RU 2003125647 A RU2003125647 A RU 2003125647A
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formula
acid
tert
compound
cyano
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RU2269515C2 (ru
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Джой МЕТЬЮ (IN)
Джой МЕТЬЮ
Ганеш САМБАСИВАМ (IN)
Ганеш САМБАСИВАМ
Мадхаван СРИДХАРАН (IN)
Мадхаван СРИДХАРАН
Сумитра СРИНАТ (IN)
Сумитра СРИНАТ
Сандхиа ЮДЖИРЕ (IN)
Сандхиа ЮДЖИРЕ
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Байокон Лимитид (IN)
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    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—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 two 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (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)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrrole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Claims (7)

1. Способ синтеза аторвастатина, полукальциевой соли [R-(R*,R*)]-2-(4-фторфенил)-β,δ-дигидрокси-5-(1-метилэтил)-3-фенил-4-[(фениламино)карбонил]-1Н-пиррол-1-гептановой кислоты формулы XII, отличающийся тем, что проводят взаимодействие предварительно полученного защищенного бороната (4R)-трет-бутилового эфира 7-амино-3,5-дигидроксигептановой кислоты формулы Х с 4-фтор-α-[2-метил-1-оксопропил]-γ-оксо-N-β-дифенил-бензолбутанамидом формулы IV в смеси растворителей, которые выбирают из группы, содержащей ксилол, циклогексан, метил-трет-бутиловый эфир, диизопропиловый эфир, ацетонитрил, в присутствии катализатора, выбранного из группы, содержащей пивалиновую кислоту, трифторметилсульфоновую кислоту, метансульфоновую кислоту или п-толуолсульфоновую кислоту, с образованием промежуточного соединения формулы XI, затем осуществляют гидролиз соединения формулы XI, после чего получают кальциевую соль целевого продукта.
2. Способ по п.1, отличающийся тем, что соединение формулы X, в котором защитную группу R выбирают из C6H5 или замещенных фенилов, получают взаимодействием этилового эфира 4-циано-3-гидроксимасляной кислоты формулы V с дигидропираном с образованием защищенного эфира 4-циано-3-(O-тетрагидропиранил)масляной кислоты формулы VI, взаимодействием соединения формулы VI с трет-бутилацетатом в присутствии основания при температуре от -30 до -80°С с образованием трет-бутилового эфира 6-циано-5-гидрокси-3-оксо-гексановой кислоты формулы VII, восстановлением соединения формулы VII с образованием трет-бутиловогоэфира6-циано-3,5-дигидрокси-гексановойкислотыформулы VIII, превращением соединения формулы VIII в защищенный боронат (4R)-трет-бутилового эфира 6-циано-3,5-дигидроксигексановой кислоты формулы IX и восстановлением соединения формулы IX с образованием защищенного бороната (4R)-трет-бутилового эфира 7-амино-3,5-дигидроксигептановой кислоты формулы X.
3. Способ по п.2, отличающийся тем, что восстановление проводят с использованием восстанавливающего агента, который выбирают из группы, содержащей боргидрид цинка.
4. Способ по п.2, отличающийся тем, что защитную группу для получения защищенного бороната выбирают из группы, содержащей фенилбороновую кислоту, толилбороновую кислоту или 3-нитробензолбороновую кислоту.
5. Промежуточный фенилборонат (4R)-трет-бутилового эфира 6-циано-3,5-дигидроксигексановой кислоты формулы IX
Figure 00000001
где R выбирают из C6H5 или замещенных фенилов.
6. Промежуточный фенилборонат (4R)-трет-бутилового эфира 7-амино-3,5-дигидроксигептановой кислоты формулы Х
Figure 00000002
где R выбирают из C6H5 или замещенных фенилов.
7. Промежуточное соединение формулы XI
Figure 00000003
где R выбирают из C6H5 или замещенных фенилов.
RU2003125647/04A 2001-01-19 2001-06-14 Способ синтеза аторвастатина и промежуточный фенилборонат (варианты) RU2269515C2 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PCT/IN2001/000006 WO2002057229A1 (en) 2001-01-19 2001-01-19 FORM V CRYSTALLINE [R-(R*,R*)]-2-(4-FLUOROPHENYL)-ß,$G(D)-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1- HEPTANOIC ACID HEMI CALCIUM SALT. (ATORVASTATIN)
INPCT/IN01/00006 2001-01-19

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US (1) US6867306B2 (ru)
EP (1) EP1351963B1 (ru)
JP (1) JP2004517900A (ru)
AT (1) ATE478079T1 (ru)
BR (1) BR0116785A (ru)
CA (1) CA2436122A1 (ru)
CZ (1) CZ20031946A3 (ru)
DE (1) DE60142854D1 (ru)
MX (1) MXPA03006475A (ru)
RU (1) RU2269515C2 (ru)
WO (2) WO2002057229A1 (ru)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7411075B1 (en) 2000-11-16 2008-08-12 Teva Pharmaceutical Industries Ltd. Polymorphic form of atorvastatin calcium
EP1332130A4 (en) * 2000-11-03 2004-01-21 Teva Pharma HEMICALCIC ATORVASTATIN FORM VII
US7501450B2 (en) * 2000-11-30 2009-03-10 Teva Pharaceutical Industries Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
IL156055A0 (en) 2000-11-30 2003-12-23 Teva Pharma Novel crystal forms of atorvastatin hemi calcium and processes for their preparation as well as novel processes for preparing other forms
HUP0302519A3 (en) 2000-12-27 2008-10-28 Teva Pharma Crystalline forms of atorvastatin, process for their preparation and pharmaceutical compositions containing them
UA74075C2 (en) 2001-06-29 2005-10-17 Warner Lambert Co NOVEL CRYSTALLINE FORMS [R-(R*,R*)]-2-(4-FLUOROPHENYL)-b, d-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1??-PYRROLE-1-HEPTANOIC ACID CALCIUM SALT (2:1)(ATORVASTATIN) (VARIANTS)
US7074818B2 (en) 2001-07-30 2006-07-11 Dr. Reddy's Laboratories Limited Crystalline forms VI and VII of Atorvastatin calcium
JP2005500351A (ja) * 2001-07-30 2005-01-06 ドクター・レディーズ・ラボラトリーズ・リミテッド 結晶形態ｖｉおよびｖｉｉのアトルバスタチンカルシウム
US7361772B2 (en) * 2001-08-16 2008-04-22 Biocon Limited Process for the production of atorvastatin calcium
EP1480950A4 (en) * 2002-02-15 2005-05-18 Teva Pharma NOVEL HEMI-CALCIUM CRYSTALLINE FORMS OF ATORVASTATIN AND METHODS FOR THEIR PREPARATION, AS WELL AS NEW METHODS FOR THE PREPARATION OF FORORVASTATIN HEMI-CALCIUM FORMS I, VIII AND IX
DK1478650T3 (da) * 2002-02-25 2010-01-25 Biocon Ltd Nye boronatestere
WO2004108660A1 (en) * 2003-06-09 2004-12-16 Biocon Limited Novel halo-substituted active methylene compounds
EP1424324A1 (en) * 2002-11-28 2004-06-02 Teva Pharmaceutical Industries Limited Crystalline form F of Atorvastatin hemi-calcium salt
EP1572643A2 (en) * 2002-11-28 2005-09-14 Teva Pharmaceutical Industries Ltd. Crystalline form f of atorvastatin hemi-calcium salt
EP1636183A1 (en) * 2003-05-16 2006-03-22 Ambit Biosciences Corporation Pyrrole compounds and uses thereof
US20040248972A1 (en) * 2003-05-16 2004-12-09 Ambit Biosciences Corporation Compounds and uses thereof
US20050182125A1 (en) * 2003-05-16 2005-08-18 Ambit Biosciences Corporation Pyrrole compounds and uses thereof
AU2003238683A1 (en) * 2003-05-26 2004-12-13 Biocon Limited Novel process for preparation of (6-(2-amino-ethyl)-2-aryl-(1,3,2)dioxaborinan-4-yl)- acetic esters
US7790197B2 (en) 2003-06-09 2010-09-07 Warner-Lambert Company Llc Pharmaceutical compositions of atorvastatin
US7655692B2 (en) 2003-06-12 2010-02-02 Pfizer Inc. Process for forming amorphous atorvastatin
US20050271717A1 (en) 2003-06-12 2005-12-08 Alfred Berchielli Pharmaceutical compositions of atorvastatin
ES2739493T3 (es) 2004-05-05 2020-01-31 Pfizer Prod Inc Formas de sal de de atorvastatina con benetamina
AU2005263550C1 (en) * 2004-07-16 2013-01-17 Lek Pharmaceuticals D.D. Oxidative degradation products of atorvastatin calcium
EP1771412A2 (en) 2004-07-20 2007-04-11 Warner-Lambert Company LLC Crystalline forms of [r-(r*)]-2-(4-fluorophenyl)-bet a,gamma-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-hept anoic acid calcium salt (2:1)
JP2008510798A (ja) * 2004-08-27 2008-04-10 バイオコン・リミテッド 非晶質アトルバスタチンカルシウムのための方法
CN101048141A (zh) 2004-10-28 2007-10-03 沃尼尔·朗伯有限责任公司 形成非晶形的阿托伐他汀的方法
EP1671947A1 (en) * 2004-12-20 2006-06-21 Ratiopharm GmbH Process for preparing pyrrole derivatives and intermediates
EP1705175A1 (en) * 2005-03-24 2006-09-27 ratiopharm GmbH Process for preparing C5 products and their use for Atorvastatin synthesis
CA2547216A1 (en) 2005-09-21 2007-03-21 Renuka D. Reddy Process for annealing amorphous atorvastatin
US8084488B2 (en) * 2005-11-21 2011-12-27 Pfizer Inc. Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid magnesium
TW200745026A (en) 2005-12-13 2007-12-16 Teva Pharma Crystal form of atorvastatin hemi-calcium and processes for preparation thereof
EP1810667A1 (en) 2006-01-20 2007-07-25 KRKA, tovarna zdravil, d.d., Novo mesto Pharmaceutical composition comprising amorphous atorvastatin
KR100763770B1 (ko) 2006-05-29 2007-10-08 조동옥 아토르바스타틴 합성에 유용한 광학활성 중간체의 제조방법
EP2066788B1 (en) 2006-10-02 2014-07-23 Codexis, Inc. Compositions and methods for producing stereoisomerically pure statins and synthetic intermediates therefor
KR100881617B1 (ko) * 2007-02-22 2009-02-17 (주) 성운파마코피아 아토바스타틴 제조를 위한 중간체 및 그의 제조방법
KR100933172B1 (ko) 2007-11-30 2009-12-21 씨제이제일제당 (주) 아토르바스타틴 칼슘염의 개선된 제조방법
EP2075246A1 (en) 2007-12-27 2009-07-01 M. J. Institute of Research A process for preparation of amorphous form of atorvastatin hemi-calcium salt
KR100850558B1 (ko) * 2008-01-02 2008-08-06 조동옥 아토르바스타틴의 효율적인 제조방법
KR101339648B1 (ko) * 2012-05-10 2013-12-09 (주) 에프엔지리서치 신규한 아토바스타틴 중간체 및 이를 이용한 아토바스타틴의 제조 방법
CN104983702A (zh) * 2015-07-23 2015-10-21 青岛蓝盛洋医药生物科技有限责任公司 一种治疗高胆固醇血症的药物阿托伐他汀钙组合物片剂
CN111909048B (zh) 2020-09-07 2021-03-16 浙江宏元药业股份有限公司 一种多组分一锅法合成阿托伐他汀钙中间体的方法

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US573995A (en) * 1896-12-29 Automatic vehicle-brake
US4681893A (en) * 1986-05-30 1987-07-21 Warner-Lambert Company Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
US5216174A (en) * 1988-02-22 1993-06-01 Warner-Lambert Co. Process for trans-6-[12-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
US5124482A (en) * 1988-02-22 1992-06-23 Warner-Lambert Company Process for trans-6-(2-substituted-pyrrol-1-yl)alkyl)pyran-2-one inhibitors of cholesterol synthesis
US5149837A (en) * 1988-02-22 1992-09-22 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
US5097045A (en) 1989-02-01 1992-03-17 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
US5245047A (en) * 1988-02-22 1993-09-14 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
US5003080A (en) * 1988-02-22 1991-03-26 Warner-Lambert Company Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one inhibitors of cholesterol synthesis
US5094045A (en) * 1988-07-27 1992-03-10 University Of Hawaii Termite barrier
FI94339C (fi) 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
JP2542941B2 (ja) * 1990-02-02 1996-10-09 チッソ株式会社 光学活性ヒドロキシラクトン類の製造方法
US5248793A (en) * 1990-10-17 1993-09-28 Warner-Lambert Company Process for the synthesis of (4R-cis)-1,1-dimethylethyl 6-iodomethyl or 6-(phenyl-substituted)sulfonyloxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate
US5103024A (en) * 1990-10-17 1992-04-07 Warner-Lambert Company Process for the synthesis of (4r-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate
CA2049536C (en) * 1991-05-13 1999-07-06 Rawle I. Hollingsworth Process for the preparation of 3,4-dihydroxybutanoic acid and salts thereof
US5155251A (en) * 1991-10-11 1992-10-13 Warner-Lambert Company Process for the synthesis of (5R)-1,1-dimethylethyl-6-cyano-5-hydroxy-3-oxo-hexanoate
US5298627A (en) * 1993-03-03 1994-03-29 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
HRP960313B1 (en) * 1995-07-17 2002-08-31 Warner Lambert Co Form iii crystalline (r- (r*, r*)-2- (4-fluorophenyl) -beta-delta-hydroxy-5-(1-methylethyl) -3-phenyl-4- ((phenylamino) carbonyl -1h-pyrrole-1-heptanoic acid calcium salt (2:1)
SI0848705T1 (en) * 1995-07-17 2002-04-30 Warner-Lambert Company Crystalline r-(r*,r*))-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4- (phenylamino)carbonyl)-1h-pyrrole-1-heptanoic acid hemi calcium salt (atorvastatin)
HRP960312B1 (en) 1995-07-17 2001-10-31 Warner Lambert Co NOVEL PROCESS FOR THE PRODUCTION OF AMORPHOUS /R-(R*, R*)/-2-(4-FLUOROPHENYL)-"beta", "delta"-DIHYDROXY-5-PHENYL-4-/(PHENYLAMINO)CARBONYL/-1H-PYRROLE -1-HEPTANOIC ACID CALCIUM SALT (2 : 1)
US5998633A (en) * 1996-07-29 1999-12-07 Warner-Lambert Company Process for the synthesis of protected esters of (S)-3,4-dihydroxybutyric acid
SI20305A (sl) 1999-08-06 2001-02-28 LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. Kristali natrijeve soli pravastatina
AU764048B2 (en) 1999-03-08 2003-08-07 Merck & Co., Inc. Crystalline hydrated dihydroxy open-acid simvastatin calcium salt
HU227840B1 (en) * 1999-05-06 2012-05-02 Egis Gyogyszergyar Nyilvanosan M Kod Ruszvunytarsasag Intermediates of atorvastatin synthesis and process for producing them
HU226640B1 (en) 1999-10-18 2009-05-28 Egis Gyogyszergyar Nyilvanosan Process for producing amorphous atorvastatin calcium salt
ES2349364T3 (es) * 1999-11-17 2010-12-30 Teva Pharmaceutical Industries, Ltd. Procedimiento para la preparación de una forma polimórfica de atorvastatina cálcica.
SI20425A (sl) 1999-12-10 2001-06-30 LEK tovarna farmacevtskih in kemi�nih izdelkov d.d. Priprava amorfnega atorvastatina
AU2000254249A1 (en) 2000-03-28 2001-10-08 Biocon India Limited Synthesis of (r-(r*,r*))-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-
PL362981A1 (en) 2000-11-16 2004-11-02 Teva Pharmaceutical Industries Ltd. Hydrolysis of [r(r*,r*)]-2-(4-fluorophenyl)-beta,delta -dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid esters with calcium hydroxide
US6777552B2 (en) 2001-08-16 2004-08-17 Teva Pharmaceutical Industries, Ltd. Processes for preparing calcium salt forms of statins
WO2002057228A1 (en) 2001-01-17 2002-07-25 Biocon India Limited Atorvastatin calcium
SK792004A3 (sk) 2001-07-06 2005-03-04 Teva Pharmaceutical Industries Ltd. Syntéza a medziprodukty derivátov 3,5-dihydroxyheptánovej kyseliny
IL159719A0 (en) 2001-07-06 2004-06-20 Teva Pharma Process for the preparation of 7-amino syn 3,5-dihydroxy heptanoic acid derivatives via 6-cyano syn 3,5-dihydroxy hexanoic acid derivatives
CN101880227A (zh) 2001-07-06 2010-11-10 西巴特殊化学品控股有限公司 一种用于制备适合于制备他汀类衍生物的中间体化合物的方法及其中间体
NZ529913A (en) 2001-08-16 2005-03-24 Teva Pharma Processes for preparing calcium salt forms of statins
KR20040101229A (ko) 2002-02-14 2004-12-02 랜박시 래보러터리스 리미티드 알칼리 금속 첨가에 의해 안정화된 아토르바스타틴 배합물

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WO2002057229A1 (en) 2002-07-25
US6867306B2 (en) 2005-03-15
MXPA03006475A (es) 2004-10-15
WO2002057274A1 (en) 2002-07-25
EP1351963B1 (en) 2010-08-18
BR0116785A (pt) 2004-03-09
JP2004517900A (ja) 2004-06-17
US20040072893A1 (en) 2004-04-15
CA2436122A1 (en) 2002-07-25
DE60142854D1 (de) 2010-09-30
EP1351963A1 (en) 2003-10-15

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