[go: up one dir, main page]

WO1989007598A3 - Procede ameliore de preparation d'inhibiteurs trans-6-[2-(pyrrol substitue-1-yl)alkyle]pyran-2-one de synthese de cholesterol - Google Patents

Procede ameliore de preparation d'inhibiteurs trans-6-[2-(pyrrol substitue-1-yl)alkyle]pyran-2-one de synthese de cholesterol Download PDF

Info

Publication number
WO1989007598A3
WO1989007598A3 PCT/US1989/000719 US8900719W WO8907598A3 WO 1989007598 A3 WO1989007598 A3 WO 1989007598A3 US 8900719 W US8900719 W US 8900719W WO 8907598 A3 WO8907598 A3 WO 8907598A3
Authority
WO
WIPO (PCT)
Prior art keywords
trans
pyran
oxo
improved process
pyrrol
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1989/000719
Other languages
English (en)
Other versions
WO1989007598A2 (fr
Inventor
Donald Eugene Butler
Carl Francis Deering
Alan Millar
Thomas Norman Nanninga
Bruce David Roth
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Warner Lambert Co LLC
Original Assignee
Warner Lambert Co LLC
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=26855024&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO1989007598(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Warner Lambert Co LLC filed Critical Warner Lambert Co LLC
Priority to KR1019970702618A priority Critical patent/KR0123813B1/ko
Priority to KR1019970702617A priority patent/KR970011579B1/ko
Priority to KR1019970702620A priority patent/KR0137884B1/ko
Priority to AU33496/89A priority patent/AU621874B2/en
Priority to KR1019970702619A priority patent/KR970011462B1/ko
Publication of WO1989007598A2 publication Critical patent/WO1989007598A2/fr
Priority to KR89701946A priority patent/KR970011578B1/ko
Publication of WO1989007598A3 publication Critical patent/WO1989007598A3/fr
Priority to DK199001970A priority patent/DK175135B1/da
Priority to FI904118A priority patent/FI94958C/fi
Priority to NO903667A priority patent/NO177566C/no
Anticipated expiration legal-status Critical
Priority to FI941550A priority patent/FI93958C/fi
Priority to NO941725A priority patent/NO177706C/no
Priority to NO943057A priority patent/NO177423C/no
Priority to NO951075A priority patent/NO180119C/no
Priority to NO963245A priority patent/NO302296B1/no
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
    • C07C235/80—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms having carbon atoms of carboxamide groups and keto groups bound to the same carbon atom, e.g. acetoacetamides
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • 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)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrrole Compounds (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Steroid Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

On a mis au point un procédé amélioré de préparation de trans-6-[2-(pyrrol substitué-1-yl) alkyle]pyran-2-ones au moyen d'une nouvelle synthèse, permettant de transformer 1,6-heptadiène-4-ol en huit opérations, en produits voulus. On a également mis au point un procédé amélioré de préparation de (2R-trans) et trans-(U)-5-(4-fluoro-phényle)-2-(1-méthylèthyle)-N,4-diphényl-1-[2-(têtrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)éthyle]-1H-pyrrole-3-carboxamide au moyen d'une nouvelle synthèse, permettant de transformer 4-méthyl-3-oxo-N-phénylpentanamide en huit opérations, en le produit voulu, ou dans un autre mode de réalisation de transformer 4-fluoro-alpha-[2-méthyl-1-oxopropyle]-gamma-oxo-N,beta-diphénylbenzènebutaneamide en une étape en le produit voulu. On a, en outre, mis au point un procédé de préparation de (2R-trans)-5-(4-flurophényle)-2-(1-méthyléthyle)-N,4-diphényle-1-[2-(têtrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)éthyle]-1H-pyrrole-3-carboxamide, à partir de (R)-4-cyano-3-[[(1,1-diméthyléthyle)diméthylsilyle]oxy]acide butanoïque, ainsi que d'autres intermédiaires de valeur utilisés dans les procédés.
PCT/US1989/000719 1988-02-22 1989-02-22 Procede ameliore de preparation d'inhibiteurs trans-6-[2-(pyrrol substitue-1-yl)alkyle]pyran-2-one de synthese de cholesterol Ceased WO1989007598A2 (fr)

Priority Applications (14)

Application Number Priority Date Filing Date Title
KR1019970702618A KR0123813B1 (ko) 1988-02-22 1989-02-22 콜레스테롤 합성 억제제인 트란스-6-[2-(치환 피롤-1-일)알킬]피란-2-온의 개량된 제조 방법
KR1019970702617A KR970011579B1 (ko) 1988-02-22 1989-02-22 콜레스테롤 합성 억제제인 트란스-6-[2-(치환 피롤-1-일)알킬]피란-2-온의 개량된 제조방법
KR1019970702620A KR0137884B1 (ko) 1988-02-22 1989-02-22 콜레스테롤 합성 억제제인 트란스-6-[2-(치환-피롤-1-일)알킬] 피란-2-온의 개량된 제조 방법
AU33496/89A AU621874B2 (en) 1988-02-22 1989-02-22 Improved process for trans-6-(2-(substituted-pyrrol-1-yl) alkyl)pyran-2-one inhibitors of cholesterol synthesis
KR1019970702619A KR970011462B1 (ko) 1988-02-22 1989-02-22 콜레스테롤 합성 억제제인 트란스-6-[2-(치환 피롤-1-일)알킬]피란-2-온의 개량된 제조 방법
KR89701946A KR970011578B1 (en) 1988-02-22 1989-10-23 Improved process for trans-6-£2-(substituted-pyrrol-1-yl)alkyl|pyran-2-one inhibitors of cholesterol synthesis
DK199001970A DK175135B1 (da) 1988-02-22 1990-08-17 Forbedret fremgangsmåde, mellemprodukter og blandinger af mellemprodukter til fremstilling af trans-6-[2-(substitueret-pyrrol-1-yl)alkyl]pyran-2-on-inhibitorer af cholesterolsyntese
FI904118A FI94958C (fi) 1988-02-22 1990-08-20 Parannettu menetelmä trans-6-/2-(substituoitu pyrrol-1-yyli)alkyyli/pyran-2-onien valmistamiseksi
NO903667A NO177566C (no) 1988-02-22 1990-08-21 Nye 1,3-dioksan-derivater
FI941550A FI93958C (fi) 1988-02-22 1994-04-05 Parannettu menetelmä trans-5-(4-fluorifenyyli)-2-(1-metyylietyyli)-N,4-difenyyli-1-(2-(tetrahydro-4-hydroksi-6-okso-2H-pyran-2-yyli)etyyli) -1H-pyrroli-3-karboksamidin valmistamiseksi
NO941725A NO177706C (no) 1988-02-22 1994-05-09 Forbedret fremgangsmåte for fremstilling av trans-6-[2- (substituert-pyrrol-yl) alkylÅ pyran-2-on-inhibitorer for kolesterolsyntese
NO943057A NO177423C (no) 1988-02-22 1994-08-18 Forbedret fremgangsmåte for fremstilling av trans-6-[2-(substituert-pyrrol-yl)alkylÅpyran-2-on-inhibitorer for kolesterolsyntese
NO951075A NO180119C (no) 1988-02-22 1995-03-21 Utgangsmaterialer for fremstilling av trans-6-£2-(substituert-pyrrol-yl)alkyl|pyran-2-on-inhibitorer for kolesterolsyntese
NO963245A NO302296B1 (no) 1988-02-22 1996-08-02 Utgangsmaterialer for fremstilling av trans-6-£2-(substituert-pyrrol-yl)alkyl|pyran-2-on-inhibitorer for kolesterolsyntese

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US15843988A 1988-02-22 1988-02-22
US158,439 1988-02-22
US07/303,733 US5003080A (en) 1988-02-22 1989-02-01 Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one inhibitors of cholesterol synthesis
US303,733 1989-02-01

Publications (2)

Publication Number Publication Date
WO1989007598A2 WO1989007598A2 (fr) 1989-08-24
WO1989007598A3 true WO1989007598A3 (fr) 1989-11-02

Family

ID=26855024

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1989/000719 Ceased WO1989007598A2 (fr) 1988-02-22 1989-02-22 Procede ameliore de preparation d'inhibiteurs trans-6-[2-(pyrrol substitue-1-yl)alkyle]pyran-2-one de synthese de cholesterol

Country Status (16)

Country Link
US (1) US5003080A (fr)
EP (2) EP0330172B1 (fr)
JP (2) JP2843627B2 (fr)
KR (1) KR970011578B1 (fr)
AT (1) ATE109777T1 (fr)
AU (2) AU635171B2 (fr)
CA (1) CA1330441C (fr)
DE (1) DE68917336T2 (fr)
DK (1) DK175135B1 (fr)
ES (1) ES2058356T3 (fr)
FI (2) FI94958C (fr)
HK (1) HK1000732A1 (fr)
IE (1) IE63994B1 (fr)
NZ (1) NZ228050A (fr)
PT (1) PT89774B (fr)
WO (1) WO1989007598A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE40667E1 (en) 1989-07-21 2009-03-17 Warner-Lambert Company Llc [R-(R*R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, its lactone form and salts thereof

Families Citing this family (114)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5128366A (en) * 1990-07-05 1992-07-07 Shinogi & Co., Ltd. Pyrrole derivatives
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
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
JP3171931B2 (ja) * 1992-06-02 2001-06-04 高砂香料工業株式会社 （Ｒ）−（−）−４−シアノ−３−ヒドロキシ酪酸ｔ−ブチルエステル及びその製造方法
JP3076154B2 (ja) 1992-08-13 2000-08-14 高砂香料工業株式会社 （３ｒ，５ｓ）−３，５，６−トリヒドロキシヘキサン酸誘導体及びその製造方法
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
US5385929A (en) * 1994-05-04 1995-01-31 Warner-Lambert Company [(Hydroxyphenylamino) carbonyl] pyrroles
GB9512837D0 (en) * 1995-06-23 1995-08-23 Zeneca Ltd reduction of ketone groups
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)
US6087511A (en) * 1996-07-16 2000-07-11 Warner-Lambert Company Process for the production of amorphous [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl )-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid) calcium salt (2:1)
BR9813760A (pt) * 1997-12-19 2000-10-03 Warner Lambert Export Limited Processo para a sìntese de 1,3-dióis
CA2329893A1 (fr) * 1998-04-30 1999-11-11 Kaneka Corporation Procede de production de derives d'acide acetique 6-cyanomethyl-1,3-dioxane-4
HU227840B1 (en) * 1999-05-06 2012-05-02 Egis Gyogyszergyar Nyilvanosan M Kod Ruszvunytarsasag Intermediates of atorvastatin synthesis and process for producing them
IN191236B (fr) 1999-05-25 2003-10-11 Ranbaxy Lab Ltd
US7411075B1 (en) * 2000-11-16 2008-08-12 Teva Pharmaceutical Industries Ltd. Polymorphic form of atorvastatin calcium
IL149087A0 (en) 1999-12-17 2002-11-10 Warner Lambert Res & Dev Ie A factory scale process for producing crystalline atorvastatin trihydrate hemi calcium
EP1242373B1 (fr) 1999-12-17 2006-03-15 Pfizer Science and Technology Ireland Limited Procede pour produire de l'atorvastatine calcique cristallin
US7300775B2 (en) 1999-12-29 2007-11-27 Verenium Corporation Methods for producing α-substituted carboxylic acids using nitrilases and strecker reagents
US7608445B1 (en) 1999-12-29 2009-10-27 Verenium Corporation Nitrilases, nucleic acids encoding them and methods for making and using them
US7521216B2 (en) * 1999-12-29 2009-04-21 Verenium Corporation Nitrilases and methods for making and using them
US20040014195A1 (en) * 1999-12-29 2004-01-22 Diversa Corporation Nitrilases, nucleic acids encoding them and methods for making and using them
GB0003305D0 (en) 2000-02-15 2000-04-05 Zeneca Ltd Pyrimidine derivatives
WO2001072706A1 (fr) * 2000-03-28 2001-10-04 Biocon India Limited Synthese de l'acide [r-(r*,r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoique sous forme de sel hemi-calcique (atorvastatine)
DE60136095D1 (de) 2000-11-16 2008-11-20 Teva Pharma Hydrolyse von är(r*,r*)ü-2-(4-fluorphenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-ä(phenylamino)carbonylü-1h-pyrrol-heptansäureestern mit calciumhydroxid
US6777552B2 (en) * 2001-08-16 2004-08-17 Teva Pharmaceutical Industries, Ltd. Processes for preparing calcium salt forms of statins
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
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
US6476235B2 (en) 2001-01-09 2002-11-05 Warner-Lambert Company Process for the synthesis of 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide
EP1724256A3 (fr) * 2001-01-09 2007-03-21 Warner-Lambert Company LLC Nouveau procédé pour la synthèse de phenylamide d'acide de 5-(4-fluorophenyl)-1-(2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-YL)-ethyl)-2-isopropyl-4-phenyl-1 H-pyrrole-3-carboxylique
WO2002057229A1 (fr) * 2001-01-19 2002-07-25 Biocon India Limited FORME V CRISTALLINE DE SEL HEMICALCIQUE D'ACIDE [R-(R*,R*)]-2-(4-FLUOROPHENYL)-ß,$G(D)-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPTANOIQUE (ATORVASTATINE)
SI20814A (sl) * 2001-01-23 2002-08-31 LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. Priprava amorfnega atorvastatina
SI20848A (sl) 2001-03-14 2002-10-31 Lek, Tovarna Farmacevtskih In Kemijskih Izdelkov, D.D. Farmacevtska formulacija, ki vsebuje atorvastatin kalcij
AP1571A (en) 2001-06-29 2006-02-10 Warner Lambert Co Crystalline forms of 'R-(R* ,R*)!-2-(4- fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-'phenylamino)carbonyl!-1H-pyrrole-1-heptanoic acid calcium salt (2:1) (atorvastatin)
AU2002325845A1 (en) * 2001-07-04 2003-01-21 Ciba Specialty Chemicals Holding Inc. Preparation process for atorvastatin and intermediates
JP2004533479A (ja) 2001-07-06 2004-11-04 チバ　スペシャルティ　ケミカルズ　ホールディング　インコーポレーテッド スタチン誘導体、特に７−アミノ３，５−ジヒドロキシヘプタン酸誘導体及びその中間体の合成に有用な中間体の調製方法
PL366610A1 (en) 2001-07-06 2005-02-07 Teva Pharmaceutical Industries Ltd. Process for the preparation of 7-amino syn 3,5-dihydroxy heptanoic acid derivatives via 6-cyano syn 3,5-dihydroxy hexanoic acid derivatives
DK1404642T3 (da) 2001-07-06 2010-05-17 Basf Se Fremgangsmåde til fremstillimg af 7-amino-syn-3,5-dihydroxyheptansyrederivater, mellemprodukter derfor og fremgangsmåder til deres fremstilling
HRP20040077A2 (en) 2001-07-30 2004-06-30 Reddys Lab Ltd Dr Crystalline forms vi and vii of atorvastatin-calcium
US20030114497A1 (en) * 2001-07-31 2003-06-19 Laman Alani Pharmaceutical compositions of amlodipine and atorvastatin
AU2001284385A1 (en) * 2001-08-31 2003-03-10 Morepen Laboratories Ltd. An improved process for the preparation of amorphous atorvastatin calcium salt (2:1)
HU227124B1 (en) * 2001-09-14 2010-07-28 Egis Gyogyszergyar Nyilvanosan Polymorphs of 1-pyrrole derivative, intermediate for the preparation of atorvastatin
US20050014954A1 (en) * 2001-11-22 2005-01-20 Reinhold Ohrlein Pyrrole synthesis
US20060020137A1 (en) * 2001-11-29 2006-01-26 Limor Tessler Novel crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
UA77990C2 (en) * 2001-12-12 2007-02-15 Crystalline calcium salt of (2:1) [r-(r*,r*)]-2-(4-fluorophenyl)-?,?-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrroleheptanic acid
CZ296967B6 (cs) 2002-02-01 2006-08-16 Zentiva, A.S. Zpusob výroby amorfní formy hemivápenaté soli (3R,5R) 7-[3-fenyl-4-fenylkarbamoyl-2-(4-fluorfenyl)-5-isopropylpyrrol-1-yl]-3,5-dihydroxyheptanové kyseliny (atorvastatinu)
PL372241A1 (en) * 2002-02-19 2005-07-11 Teva Pharmaceutical Industries Ltd. Processes for desolvating solvates of atorvastatin hemi-calcium and atorvastatin hemi-calcium essentially free of organic solvent
DE10212492B4 (de) * 2002-03-21 2012-02-02 Daimler Ag Kolbenpumpe
US7932064B2 (en) * 2002-06-13 2011-04-26 Verenium Corporation Processes for making (R)-ethyl 4-cyano-3-hydroxybutyric acid
ATE368661T1 (de) * 2002-08-06 2007-08-15 Warner Lambert Co Verfahren zur herstellung von 5-(4-fluorphenyl)-1- 2-((2r,4r)-4-hydroxy-6-oxo etrahydropyran-2- yl)ethylö-2-isopropyl-4-phenyl-1h-pyrrol-3- carbonsäurephenylamid
JP2006503024A (ja) * 2002-09-03 2006-01-26 モレペン、ラボラトリーズ、リミテッド Ｖｉ型アトルバスタチンカルシウムまたはその水和物
HRP20020885B1 (en) * 2002-11-11 2007-05-31 GlaxoSmithKline istra�iva�ki centar Zagreb d.o.o. SUBSTITUTED 9a-N-{N'-[4-(SULFONYL)PHENYLCARBAMOYL]}DERIVATIVES 9-DEOXO-9-DIHYDRO-9a-AZA-9a-HOMOERITHROMYCIN A AND 5-O-DESOZAMINYL-9-DEOXO-9-DIHYDRO-9a-AZA-9a-HOMOERITHRONOLIDE A
EP1480943A2 (fr) * 2002-11-15 2004-12-01 Teva Pharmaceutical Industries Limited Synthese d'acides 3,5-dihydroxy-7-pyrrol-1-yle heptanoiques
CA2521903A1 (fr) * 2003-04-14 2004-10-21 Warner-Lambert Company Llc Procede de preparation de phenylamide d'acide carboxylique 5-(4-fluorophenyl)-1-[2-((2r,4r)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)ethyl]-2-isopropyl-4-phenyl-1h-pyrrole-3
DE602004011921T2 (de) 2003-05-02 2009-02-19 Dsm Ip Assets B.V. Verfahren zur herstellung von (4-hydroxy-6-oxo-tetrahydropyran-2-yl) acetonitril und dessen derivaten
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
WO2004110357A2 (fr) * 2003-05-16 2004-12-23 Ambit Biosciences Corporation Composes heterocycliques et leurs utilisations
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
US20040253305A1 (en) * 2003-06-12 2004-12-16 Luner Paul E. Pharmaceutical compositions of atorvastatin
US20050271717A1 (en) 2003-06-12 2005-12-08 Alfred Berchielli Pharmaceutical compositions of atorvastatin
US7368468B2 (en) * 2003-06-18 2008-05-06 Teva Pharmaceutical Industries Ltd. Fluvastatin sodium crystal forms XIV, LXXIII, LXXIX, LXXX and LXXXVII, processes for preparing them, compositions containing them and methods of using them
WO2004113291A2 (fr) * 2003-06-18 2004-12-29 Teva Pharmaceutical Industries Ltd. Formes cristallines de sodium de fluvastatine xiv, lxxiii, lxxix, lxxx et lxxxvii, leurs procedes de preparation, compositions les contenant et leurs procedes d'utilisation
US7414141B2 (en) 2003-07-25 2008-08-19 Avecia Pharmaceuticals, Ltd. Process and intermediate compounds useful in the preparation of statins, particularly atorvastatin
CN101318923A (zh) * 2003-09-17 2008-12-10 沃尼尔·朗伯有限责任公司 [R－(R*,R*)]－2－(4－氟苯基)－β,δ－二羟基－5－(1－甲基乙基)－3－苯基－4－[(苯基氨基)羰基]－1H－吡咯－1－庚酸的结晶形式
WO2005026107A1 (fr) * 2003-09-18 2005-03-24 Biocon Limited Nouveau processus de preparation de tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate
CA2645396A1 (fr) * 2003-12-24 2005-07-14 Teva Pharmaceutical Industries, Ltd Procede de preparation de statines a rapport syn anti eleve
US7851624B2 (en) * 2003-12-24 2010-12-14 Teva Pharamaceutical Industries Ltd. Triol form of rosuvastatin and synthesis of rosuvastatin
US20070179166A1 (en) * 2003-12-24 2007-08-02 Valerie Niddam-Hildesheim Process for preparation of statins with high syn to anti ratio
US7943786B2 (en) 2003-12-29 2011-05-17 Ljubomir Antoncic Process for preparing amorphous (4R-cis)-6-[2-[3-phenyl-4-(phenylcarbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-pyrrol-1-yl]-ethyl]-2,2-dimethyl-[1,3]-dioxane-4-yl-acetic acid
CA2456430A1 (fr) * 2004-01-28 2005-07-28 Brantford Chemicals Inc. Procede ameliore pour la preparation d'atorvastatine calcique amorphe
CA2560252C (fr) 2004-03-17 2009-08-04 Ranbaxy Laboratories Limited Procede de production d'atorvastatine calcique sous forme amorphe
AU2005232959A1 (en) * 2004-04-16 2005-10-27 Pfizer Products Inc. Process for forming amorphous atorvastatin calcium
EP3581564A1 (fr) * 2004-05-05 2019-12-18 Pfizer Products Inc. Formes de sel de diéthylamine d'acide heptanoïque [r-(r*,r*)]-2-(4-fluorophényl)-béta, delta-dihydroxy-5-(1-méthyléthyle)-3-phényl-4-[(phénylamino)carbonyl]-1h-pyrrole-1
JP5000502B2 (ja) * 2004-07-16 2012-08-15 レツク・フアーマシユーテイカルズ・デー・デー アトルバスタチンカルシウムの酸化分解生成物
JP2008506764A (ja) 2004-07-20 2008-03-06 ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー ［Ｒ−（Ｒ＊，Ｒ＊）］−２−（４−フルオロフェニル）−β、δ−ジヒドロキシ−５−（１−メチルエチル）−３−フェニル−４−［（フェニルアミノ）カルボニル］−１Ｈ−ピロール−１−ヘプタン酸カルシウム塩（２：１）の新規形態
WO2006032959A2 (fr) * 2004-08-06 2006-03-30 Glenmark Pharmaceuticals Limited Procedes de preparation de derives pyrroliques
WO2006021968A1 (fr) * 2004-08-26 2006-03-02 Biocon Limited PROCESSUS DE PRÉPARATION DE 4-FLUORO-α-[2-MÉTHYL-1-OXOPROPYL]Ϝ-OXO-N-β-AMIDE DE BUTANE DE DIPHÉNYLBENZÈNE
WO2006021969A1 (fr) 2004-08-27 2006-03-02 Biocon Limited Processus pour calcium d'atorvastatine amorphe
KR20070067175A (ko) 2004-10-28 2007-06-27 워너-램버트 캄파니 엘엘씨 무정형 아토르바스타틴 형성 방법
AU2005305460B2 (en) * 2004-11-22 2011-04-21 Dexcel Pharma Technologies Ltd. Stable atorvastatin formulations
EP1819319A1 (fr) * 2004-12-02 2007-08-22 Warner-Lambert Company LLC Compositions pharmaceutiques d'atorvastatine amorphe et leur procede de preparation
CA2498978A1 (fr) 2005-02-28 2006-08-28 Apotex Pharmachem Inc. Procede ameliore de preparation de l'atorvastatine et de produits intermediaires connexes
CA2499047A1 (fr) * 2005-03-01 2006-09-01 Apotex Pharmachem Inc. Methode de synthese d'un sel de semi-calcium d'atorvastatine
RU2409563C2 (ru) * 2005-04-08 2011-01-20 Эгиш Дьёдьсердьяр Ньильваношан Мюкёдё Ресвеньтаршашаг Новая полиморфная форма кристаллической гемикальциевой соли аторвастатина
EP1922301A1 (fr) * 2005-09-09 2008-05-21 Pfizer Science and Technology Ireland Limited Preparation d un intermediaire de l atorvastatine
EP1922315B1 (fr) * 2005-09-09 2009-05-27 Pfizer Science and Technology Ireland Limited Preparation d'un intermediaire de l' atorvastatine
ES2270722B1 (es) * 2005-09-15 2008-03-01 Ercros Industrial, S.A. Procedimiento para la obtencion de atorvastatina calcica amorfa.
US20090216029A1 (en) * 2005-09-16 2009-08-27 Yatendra Kumar Process for the production of atorvastatin calcium in amorphous form
CA2547216A1 (fr) * 2005-09-21 2007-03-21 Renuka D. Reddy Procede de recuit de l'atorvastatine amorphe
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
WO2007070667A2 (fr) * 2005-12-13 2007-06-21 Teva Pharmaceutical Industries Ltd. Forme cristalline d’hemi-calcium d’atorvastatine et procedes de fabrication de celle-ci
EP1810667A1 (fr) 2006-01-20 2007-07-25 KRKA, tovarna zdravil, d.d., Novo mesto Composition pharmaceutique contenant de l'atorvastatin amorphé
WO2007096751A1 (fr) * 2006-02-21 2007-08-30 Cadila Healthcare Limited Procédé de préparation d'atorvastatine calcique
JP2007231018A (ja) * 2006-03-01 2007-09-13 Teva Pharmaceutical Industries Ltd アトルバスタチンヘミカルシウムの結晶形の調製方法
WO2008075165A1 (fr) * 2006-12-19 2008-06-26 Pfizer Products Inc. Nouveau procédé pour la synthèse de l'acide [r-(r*, r*)]-2-(4-fluorophényl)-bêta, delta-dihydroxy-5-(1-méthyléthyl)-3-phényl-4-[(phénylamino)carbonyl]-1h-pyrrole-1-heptanoïque ou d'un sel pharmaceutiquement acceptable de celui-ci
US7834195B2 (en) * 2007-01-24 2010-11-16 Apotex Pharmachem Inc. Atorvastatin calcium propylene glycol solvates
KR100881617B1 (ko) 2007-02-22 2009-02-17 (주) 성운파마코피아 아토바스타틴 제조를 위한 중간체 및 그의 제조방법
WO2008106662A2 (fr) 2007-03-01 2008-09-04 Verenium Corporation Nitrilases, acides nucléiques les codant et procédés de fabrication et d'utilisation de ceux-ci
GB0711250D0 (en) 2007-06-12 2007-07-18 Cbz Chemicals Ltd Furanose derivatives
US20110142883A1 (en) * 2007-07-20 2011-06-16 Actavis Group Ptc Ehf Amorphous Coprecipitates of Atorvastatin Pharmaceutically Acceptable Salts
KR100921195B1 (ko) * 2007-10-25 2009-10-13 주식회사 대웅제약 아토르바스타틴의 제조 방법
EP2075246A1 (fr) 2007-12-27 2009-07-01 M. J. Institute of Research Procédé de préparation de forme amorphe de sel hémicalcium atorvastanine
KR100850558B1 (ko) * 2008-01-02 2008-08-06 조동옥 아토르바스타틴의 효율적인 제조방법
EP2279167B1 (fr) * 2008-05-29 2012-09-19 Arch Pharmalabs Limited Nouveau procédé de préparation du 4-fluoro-alpha-ý2-méthyl-1-oxopropyl¨-gamma-oxo-n- -diphénylbenzènebutanamide et des produits à partir de celui-ci
US8115015B2 (en) * 2009-01-26 2012-02-14 Cadila Healthcare Limited Process for the preparation of amorphous atorvastatin calcium
KR20120011249A (ko) 2010-07-28 2012-02-07 주식회사 경보제약 아토바스타틴 헤미칼슘염의 신규한 결정형, 이의 수화물, 및 그의 제조방법
HUE025861T2 (en) 2010-09-09 2016-05-30 Dsm Sinochem Pharm Nl Bv Salts of 7-amino-3,5-dihydroxy-heptanoic acid esters
SI2616454T1 (sl) * 2010-09-16 2015-08-31 Dsm Sinochem Pharmaceuticals Netherlands B.V. Estri heksanojskih kislin, kot vmesne spojine za pripravo atorvastatina
CN102127060B (zh) * 2010-12-17 2013-12-04 蚌埠丰原医药科技发展有限公司 一种阿托伐他汀钙中间体的制备方法
WO2013004591A1 (fr) 2011-07-01 2013-01-10 Dsm Sinochem Pharmaceuticals Netherlands B.V. Cristaux micronisés d'atorvastatine hémicalcique
EP3698797A1 (fr) 2017-10-16 2020-08-26 Tsinghua University Inhibiteur de la voie de l'acide mévalonique et composition pharmaceutique correspondante
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

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3960941A (en) * 1973-04-04 1976-06-01 Ethyl Corporation 3-Hydroxy-3,4-dicarbamoylbutyric acid and salts
US4647576A (en) * 1984-09-24 1987-03-03 Warner-Lambert Company Trans-6-[2-(substitutedpyrrol-1-yl)alkyl]-pyran-2-one inhibitors of cholesterol synthesis
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

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE40667E1 (en) 1989-07-21 2009-03-17 Warner-Lambert Company Llc [R-(R*R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, its lactone form and salts thereof

Also Published As

Publication number Publication date
FI941550A0 (fi) 1994-04-05
DE68917336D1 (de) 1994-09-15
FI904118A0 (fi) 1990-08-20
HK1000732A1 (en) 1998-04-24
IE63994B1 (en) 1995-06-28
AU1601892A (en) 1992-07-09
AU634689B2 (en) 1993-02-25
NZ228050A (en) 1992-01-29
IE890391L (en) 1989-08-22
FI941550L (fi) 1994-04-05
JP3009139B2 (ja) 2000-02-14
CA1330441C (fr) 1994-06-28
DE68917336T2 (de) 1994-12-01
DK197090D0 (da) 1990-08-17
JP2843627B2 (ja) 1999-01-06
FI94958B (fi) 1995-08-15
JPH10195071A (ja) 1998-07-28
FI94958C (fi) 1995-11-27
WO1989007598A2 (fr) 1989-08-24
DK197090A (da) 1990-10-04
JPH03502798A (ja) 1991-06-27
FI93958C (fi) 1995-06-26
ES2058356T3 (es) 1994-11-01
EP0330172B1 (fr) 1994-08-10
EP0448552A1 (fr) 1991-10-02
KR970011578B1 (en) 1997-07-12
EP0330172A3 (en) 1989-12-13
KR900700478A (ko) 1990-08-13
EP0330172A2 (fr) 1989-08-30
FI93958B (fi) 1995-03-15
AU635171B2 (en) 1993-03-11
US5003080A (en) 1991-03-26
PT89774B (pt) 1994-03-31
DK175135B1 (da) 2004-06-14
PT89774A (pt) 1989-10-04
AU1601792A (en) 1992-07-09
ATE109777T1 (de) 1994-08-15

Similar Documents

Publication Publication Date Title
WO1989007598A3 (fr) Procede ameliore de preparation d'inhibiteurs trans-6-[2-(pyrrol substitue-1-yl)alkyle]pyran-2-one de synthese de cholesterol
CA2155952A1 (fr) Nouvelle methode pour la synthese de trans-6-[2-(substituant-pyrrol-1-yl)alkyl]pyran-2-ones, inhibiteurs du cholesterol
EP1466886A3 (fr) Nouveaux sels d'inhibiteurs de la HMG-CoA reductase
EP0179559A3 (fr) Trans-6-[2-(pyrrol-1-yl)alkyl]-pyran-2-ones substitués inhibiteurs de la synthèse du cholestérol
CA2021546A1 (fr) Acide[r-(r*,r*)]-2-(4-fluorophenyl)-.beta.-.delta.-dihydroxy-5- (1-methylethyl)-3-phenyl-4-[(phenylamino)-carbonyl]-1h-pyrr ole-1-heptanoique, son_lactone ou ses sels
CA2432064A1 (fr) Nouveau procede pour la synthese de phenylamide d'acide de 5-(4-fluorophenyl)-1-[2-((2r, 4r)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1h-pyrrole-3-carboxylique
EP0306929A3 (fr) 6-[[Pyridin-3-yl substituées]alkyl]-et alkényl]-tétrahydro-4-hydroxypyran-2-ones-inhibiteurs de biosynthèse de cholestérol
NL970034I1 (nl) Trans-6-2-(3- of 4-carbonamido-gesubstitueerd pyrrool-1-yl)alkyl!-4-hydroxypyran-2-on als remmers van cholesterolsynthese.
IL187261A0 (en) Crystals of the sodium salt of pravastatin
IE881544L (en) Phosphorous-containing hmg-coa reductase inhibitors and¹intermediates
EP0283123A3 (fr) Produits intermédiaires et procédé de préparation d'inhibiteurs de réductase HMG-COA
EP0286330A3 (fr) Substance FR-900848 et sa préparation
Butler et al. Process for trans-6-(2-(substituted-pyrrol-1-yl) alkyl) pyran-2-one inhibitors of cholesterol synthesis

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AT AU DE DK FI GB JP KR LU NL NO SE US US

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH DE FR GB IT LU NL SE

AK Designated states

Kind code of ref document: A3

Designated state(s): AT AU DE DK FI GB JP KR LU NL NO SE US US

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH DE FR GB IT LU NL SE

WWE Wipo information: entry into national phase

Ref document number: 1989903348

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 904118

Country of ref document: FI

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1989903348

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1989903348

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 941550

Country of ref document: FI

WWG Wipo information: grant in national office

Ref document number: 941550

Country of ref document: FI

WWG Wipo information: grant in national office

Ref document number: 904118

Country of ref document: FI