WO2002026737A1 - Nouvelles formes polymorphes de 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate et procede de preparation associe - Google Patents

Nouvelles formes polymorphes de 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate et procede de preparation associe Download PDF

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Publication number
WO2002026737A1
WO2002026737A1 PCT/US2001/029896 US0129896W WO0226737A1 WO 2002026737 A1 WO2002026737 A1 WO 2002026737A1 US 0129896 W US0129896 W US 0129896W WO 0226737 A1 WO0226737 A1 WO 0226737A1
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Prior art keywords
pyridyl
thiazolidine
ethoxy
benzyl
methyl
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Application number
PCT/US2001/029896
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English (en)
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WO2002026737A8 (fr
Inventor
Prabhakar Chebiyyam
Ramabhadra Sarma Mamillapalli
Vyas Krishnamurthi
Vishnuvardhan Reddy Seella
Om Reddy Gaddam
Original Assignee
Dr. Reddy's Research Foundation
Cord, Janet, I.
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
Priority to CA002426117A priority Critical patent/CA2426117A1/fr
Priority to EP01971336A priority patent/EP1322647A1/fr
Priority to PL01360661A priority patent/PL360661A1/xx
Priority to KR10-2003-7004329A priority patent/KR20030082541A/ko
Priority to IL15503601A priority patent/IL155036A0/xx
Priority to NZ525498A priority patent/NZ525498A/en
Priority to UA2003043901A priority patent/UA75370C2/uk
Application filed by Dr. Reddy's Research Foundation, Cord, Janet, I. filed Critical Dr. Reddy's Research Foundation
Priority to BR0114196-1A priority patent/BR0114196A/pt
Priority to JP2002531121A priority patent/JP2004509961A/ja
Priority to HU0301161A priority patent/HUP0301161A3/hu
Priority to MXPA03002580A priority patent/MXPA03002580A/es
Priority to SK375-2003A priority patent/SK3752003A3/sk
Priority to US10/381,512 priority patent/US7241895B2/en
Priority to AU2001291232A priority patent/AU2001291232B8/en
Priority to AU9123201A priority patent/AU9123201A/xx
Publication of WO2002026737A1 publication Critical patent/WO2002026737A1/fr
Priority to IL155036A priority patent/IL155036A/en
Priority to NO20031356A priority patent/NO324968B1/no
Publication of WO2002026737A8 publication Critical patent/WO2002026737A8/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P9/10—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
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • This invention relates to novel polymorphic/pseudopolymorphic forms of 5-[4-[2-
  • the invention also relates to a pharmaceutical composition comprising the novel polymorphic form or their mixture and a pharmaceutically acceptable carrier.
  • the polymorphic forms of the present invention are more active, as antidiabetic agent, than the hitherto known 5-[4-[2-[N-methyl-N-(2- pyridyl)amino]ethoxy] benzyl] thiazolidine-2,4-dione maleate.
  • the present invention also relates to a process for the preparation of various polymorphic/pseudopolymorphic 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy] benzyl]thiazolidine-2,4-dione maleate, having the formula (I) shown below.
  • the polymorphic forms prepared by the process of the present invention are more active, as an antidiabetic agent.
  • polymorphic forms of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate, of formula (I) defined above of the present invention reduce blood glucose and has beneficial effect on coronary heart disease and atherosclerosis.
  • novel polymorphic forms of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy] benzyl]thiazolidine-2,4-dione maleate, of formula (I) defined above of the present invention are useful in reducing body weight and for the treatment and or prophylaxis of diseases such as hypertension, coronary heart disease, atherosclerosis, stroke, peripheral vascular diseases and related disorders.
  • novel polymorphic forms of 5-[4-[2-[N- methyl-N-(2-pyridyl) amino]ethoxy]benzyl]thiazolidin ' e-2,4-dione maleate, of formula (I) of the present invention can be used for the treatment of certain renal diseases including glomerulonephritis, glomeralosclerosis, nephrotic syndrome, hypertensive nephrosclerosis and nephropathy.
  • N-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate, of formula (I) are also useful for the treatment and/or prophylaxis of insulin resistance (type II diabetes), leptin resistance, impaired glucose tolerance, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, insulin resistance, coronary heart disease and other cardiovascular disorders.
  • novel polymorphic forms of 5-[4-[2-[N-methyl-N-(2- pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate, of formula (I) may also be useful as aldose reductase inhibitors, for improving cognitive functions in dementia, treating diabetic complications, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), inflammatory bowel diseases, osteoporosis, myotonic dystrophy, pancreatitis, arteriosclerosis, retinopathy, xanthoma, inflammation and for the treatment of cancer.
  • PCOS polycystic ovarian syndrome
  • novel polymorphic forms of 5-[4-[2-[N-methyl-N- (2-pyridyl)amino]ethoxy] benzyl]thiazolidine-2,4-dione maleate, of formula (I) of the present invention are useful in the treatment and or prophylaxis of the above said diseases in combination/con-comittant with one or more HMG CoA reductase inhibitors, hypolipidemic hypolipoproteinemic agents such as fibric acid derivatives, nicotinic acid, cholestyramine, colestipol, probucol.
  • polymorphism we mean to include different physical forms, crystal forms, crystalline / liquid crystalline / non-crystalline (amorphous) forms. This has especially become very interesting after observing that many antibiotics, antibacterials, tranquilizers etc., exhibit polymorphism and some/one of the polymorphic forms of a given drug exhibit superior bio-availability and consequently show much higher activity compared to other polymorphs.
  • Sertraline, Frentizole, Ranitidine, Sulfathiazole, Indomethacine etc. are some of the important examples of pharmaceuticals which exhibit polymorphism.
  • Polymorphism in drugs is a topic of current interest and is evident from the host of patents being granted. To cite a few, U.S.
  • Polymorphism in drugs is a topic of current interest and is evident from the host of patents being granted to cite a few U.S. 5,248,699 discusses about five polymorphic forms of Sertraline hydrochloride while EP 014590, describes four polymorphic forms of Frentizole EP 490648 and EP 022527, six polymorphic forms of Troglitazone WO 97/27191 also deal with the subject of polymorphism in drugs.
  • Another objective of the present invention is to provide polymorphic forms of 5-
  • PPAR ⁇ and/or PPAR ⁇ optionally inhibit HMG CoA reductase, in addition to having agonist activity against PPAR ⁇ and/or PPAR ⁇ .
  • Another objective of the present invention is to provide novel polymorphic forms of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate, their stereoisomers, pharmaceutically acceptable solvates and pharmaceutical compositions containing them or their mixtures having enhanced activities, without toxic effect or with reduced toxic effect.
  • Yet another objective of the present invention to provide a process for the preparation of novel polymorphic forms of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino] ethoxy]benzyl]thiazolidine-2,4-dione maleate, their stereoisomers, pharmaceutically acceptable solvates.
  • Still another objective of the present invention is to provide pharmaceutical compositions containing novel polymorphic forms of 5-[4-[2-[N-methyl-N-(2-pyridyl) amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate, solvates or their mixtures in combination with suitable carriers, solvents, diluents and other media normally employed in preparing such compositions.
  • the present invention relates to an observation that 5-[4-[2-[N-methyl-N-(2- pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate exhibits polymo ⁇ hism, which has not been reported till date.
  • the polymorphic Forms I, II, III and IN are obtained from different solvents like ethanol, acetone, methanol and 1,4-dioxane respectively. From powder X-ray diffraction studies Forms I, II, LU and IN are found to be crystalline in nature.
  • DSC of the polymorphic Form I shows melting endotherm at 100.53°C.
  • Form II dislays endotherm at 127.67°C.
  • Form LU exhibits melting endotherm at 126.41 °C and
  • Form TV exhibits endotherm at 125.39°C.
  • X-ray powder diffraction pattern has been obtained on a Rigaku D Max 2200 model diffractometer equiped with horizontal gonimometer in ⁇ /2 ⁇ geometry.
  • the copper K ⁇ C ⁇ l .5418A) radiation was used and the sample was scanned between 3-45 degrees 2 ⁇ .
  • the samples weighed in aluminum cells were heated from room temperature to 220°C at a heating rate of 5°C /min.
  • the empty aluminum cell was used as a reference. Dry nitrogen gas was purged through DSC cell continuously throughout the analysis at a flow rate of 30 ml/min.
  • Fig 1 is a characteristic differential scanning calorimetric thermogram of Form I
  • Fig 2 is a characteristic differential scanning calorimetric thermogram of Form II
  • Fig 3 is a characteristic differential scanning calorimetric thermogram of Form III
  • Fig 4 is a characteristic differential scanning calorimetric thermogram of Form IN
  • Fig 5 is a characteristic X-ray diffraction pattern of Form I
  • Fig 6 is a characteristic X-ray diffraction pattern of Form II
  • Fig 7 is a characteristic X-ray diffraction pattern of Form III
  • Fig 8 is a characteristic X-ray diffraction pattern of Form IN
  • Fig 9 is the multi-plot of X-ray diffraction patterns of Forms I, II, III and IN
  • Fig 10 is a characteristic infrared absorption spectrum of Form I in potassium bromide.
  • Fig 11 is a characteristic infrared absorption spectrum of Form II in potassium bromide.
  • Fig 12 is a characteristic infrared absorption spectrum of Form III in potassium bromide.
  • Fig 13 is a characteristic infrared abso ⁇ tion spectrum of Form IN in potassium bromide.
  • LR (cm -1 ) 3435 (m), 2997 (w), 2773 (m), 1750 (m), 1701 (s), 1620 (m), 1510 (m), 1362 (m), 1332 (m), 1237 (s), 1165 (m), 864 (s), 764 (s), 717 (m), 654 (m), 540 (w), Fig. (10).
  • LR 3424 (w), 3040 (w), 2947 (m), 2720 (m), 1751 (m), 1702 (s), 1641 (m), 1618 (m), 1574 (w), 1541 (w), 1412 (w), 1382 (w), 1359 (m), 1326 (m), 1265 (w), 1242 (s), 1213 (w), 1162 (s), 1067 (w), 1031 (w), 865 (s), 773 (s), 713 (s), 667 (m), 576 (w), 539 (m), (Fig. 11).
  • LR 3429 (m), 2949 (m), 2738 (m), 1747 (w), 1704 (s), 1641 (m), 1617 (m), 1513 (s), 1464 (m), 1352 (m), 1244 (s), 1178 (s), 1069 (m), 862 (w), 777 (s), 717 (m), 657 (m), 589 (w) (Fig. 12).
  • stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantiomeric form in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantiomer form or by resolving the mixture of stereoisomers by conventional methods.
  • Some of the preferred methods include use of microbial resolution, resolving the diastereomeric salts formed with chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lactic acid, and the like wherever applicable or chiral bases such as bracine, cinchona alkaloids and their derivatives and the like.
  • chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lactic acid, and the like wherever applicable or chiral bases such as bracine, cinchona alkaloids and their derivatives and the like.
  • Commonly used methods are compiled by Jaques et al in "Enantiomers, Racemates and Resolution" (Wiley Interscience, 1981. Conventional reaction conditions may be employed to convert acid into an amide; the diastereomers may be separated either by fractional crystallization or chromatography and the stereoisomers of compound of formula (I) may be prepared by hydrolyzing the pure diastereomeric amide.
  • the present invention also envisages a pharmaceutical composition comprising any of the polymo ⁇ hic Forms I to IV of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy] benzyl] thiazolidine-2,4-dione maleate, of the formula (I) and a pharmaceutically acceptable carrier .
  • the present invention also envisages a pharmaceutical composition comprising a mixture of any of polymo ⁇ hic Forms I to FV of 5-[4-[2-[N-methyl-N-(2-pyridyl) amino]ethoxy]benzyl] thiazo ⁇ dine-2,4-dione maleate, of the formula (I) and a pharmaceutically acceptable carrier .
  • the pharmaceutical composition may be in the forms normally employed, such as tablets, capsules, powders, syrups, solutions, suspensions and the like, may contain flavourants, sweeteners etc. in suitable solid or liquid carriers or diluents, or in suitable sterile media to form injectable solutions or suspensions.
  • Such compositions typically contain from 1 to 25%, preferably 1 to 15% by weight of active ingredient, the remainder of the composition being pharmaceutically acceptable carriers, diluents or solvents.
  • polymo ⁇ hic forms of the formula (I) as defined above are clinically administered to mammals, including man, via either oral, nasal, pulmonary, transdermal or parenteral, rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic solution or an ointment.
  • Administration by the oral route is preferred, being more convenient and avoiding the possible pain and irritation of injection.
  • the patient cannot swallow the medication, or abso ⁇ tion following oral administration is impaired, as by disease or other abnormality, it is essential that the drug be admimstered parenterally.
  • the dosage is in the range of about 0.01 to about 100 mg/kg body weight of the subject per day or preferably about 0.01 to about 30 mg/kg body weight per day admimstered singly or as a divided dose.
  • the optimum dosage for the individual subject being treated will be determined by the person responsible for treatment, generally smaller doses being administered initially and thereafter increments made to determine the most suitable dosage.
  • Suitable pharmaceutically acceptable carriers include solid fillers or diluents and sterile aqueous or organic solutions.
  • the active ingredient will be present in such pharmaceutical compositions in the amounts sufficient to provide the desired dosage in the range as described above.
  • the polymo ⁇ hic form can be combined with a suitable solid or liquid carrier or diluent to form capsules, tablets, powders, syrups, solutions, suspensions and the like.
  • the pharmaceutical compositions may, if desired, contain additional components such as flavourants, sweeteners, excipients and the like.
  • the polymo ⁇ hic form can be combined with sterile aqueous or organic media to form injectable solutions or suspensions.
  • solutions in sesame or peanut oil, aqueous propylene glycol and the like can be used, as well as aqueous solutions of water-soluble pharmaceutically-acceptable acid addition salts or salts with base of the compounds.
  • Aqueous solutions with the active ingredient dissolved in polyhydroxylated castor oil may also be used for injectable solutions.
  • the injectable solutions prepared in this manner can then be administered intravenously, intraperitoneally, subcutaneously, or intramuscularly, with intramuscular administration being preferred in humans.
  • the preparation may contain the polymo ⁇ hic forms of the present invention dissolved or suspended in a liquid carrier, in particular an aqueous carrier, for aerosol application.
  • a liquid carrier in particular an aqueous carrier
  • the carrier may contain additives such as solubilizing agents, such as propylene glycol, surfactants, abso ⁇ tion enhancers such as lecithin (phosphatidylcholine) or cyclodextrin or preservatives such as parabenes.
  • Tablets, dragees or capsules having talc and/or a carbohydrate carried binder or the like are particularly suitable for any oral application.
  • carriers for tablets, dragees or capsules include lactose, corn starch and/or potato starch.
  • a syrup or elixir can be used in cases where a sweetened vehicle can be employed.
  • a typical tablet production method is exemplified below:
  • ingredients 1-4 are uniformly moistened with an aqueous solution of 5 and granulated after drying under reduced pressure.
  • Ingredient 6 is added and granules are compressed by a tabletting machine to prepare 1000 tablets containing 30 mg of ingredient 1.
  • Example - 2 1 g of the 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4- dione maleate obtained by the process as described in Example- 1 was taken in 10 ml EtOH and heated on a steam bath till the solid completely dissolved. The clear solution was allowed to cool to RT over a period of 18 h to yield 80% of >99% pure polymo ⁇ hic Form I of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate.
  • Example - 3 1 g of the 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4- dione maleate obtained by the process as described in Example-1 was taken in 50 ml acetone and heated on a steam bath till the solid completely dissolved. The solution was allowed to cool to RT over a period of 18 h to yield 60%> of > 99% pure polymo ⁇ hic Form II of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate.
  • Example - 4 1 g of the 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4- dione maleate obtained by the process as described in Example-1 was dissolved in 10 ml of methanol and heated on a steam bath till the solid completely dissolved. The clear solution was filtered and allowed to cool to RT over a period of 18 h to yield 75% of > 99% pure polymo ⁇ hic Form III of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy] benzyl] thiazolidine-2,4-dione maleate.
  • Example - 5 1 g of the 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate obtained by the process as described in Example-1 was dissolved in 10 ml of m

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Abstract

L'invention concerne des nouvelles formes polymorphes/pseudo-polymorphes de 5-[4-[2[N-méthyl-N-(2-pyridyl)amino]éthoxy]benzyl] thiazolidine-2,4-dione maléate de formule (I). L'invention concerne également une composition pharmaceutique renfermant les nouvelles formes polymorphes ou un mélange de celles-ci et un adjuvant acceptable sur le plan pharmaceutique. Les formes polymorphes selon l'invention sont plus actives, comme agent anti-diabétique, que le 5-[4-[2-[N-(2-méthyl-N-(2-pyridyl)amino]éthoxy]benzyl] thiazolidine-2,4-dione maléate connu jusqu'à présent.
PCT/US2001/029896 2000-09-26 2001-09-25 Nouvelles formes polymorphes de 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate et procede de preparation associe WO2002026737A1 (fr)

Priority Applications (17)

Application Number Priority Date Filing Date Title
US10/381,512 US7241895B2 (en) 2000-09-26 2001-09-25 Polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl)amino[ethoxy]benzyl] thiazolidine-2,4-dione maleate and process for their preparation
PL01360661A PL360661A1 (en) 2000-09-26 2001-09-25 Novel polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate and process for their preparation
KR10-2003-7004329A KR20030082541A (ko) 2000-09-26 2001-09-25 5-[4-[2-[엔-메틸-엔-(2-피리딜)아미노]에톡시]벤질]티아졸리딘 4-디온 말레이트의 신규의 다형상 및 그제조방법
IL15503601A IL155036A0 (en) 2000-09-26 2001-09-25 Polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl) amino] ethoxy] benzyl] thiazolidine-2,4-dione maleate and pharmaceutical compositions containing the same
NZ525498A NZ525498A (en) 2000-09-26 2001-09-25 Novel polymorphic forms of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate and process for their preparation
UA2003043901A UA75370C2 (en) 2000-09-26 2001-09-25 Polymorphic forms of 5-[4-[2(n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2.4-dione maleate
HU0301161A HUP0301161A3 (en) 2000-09-26 2001-09-25 Novel polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate and process for their preparation
BR0114196-1A BR0114196A (pt) 2000-09-26 2001-09-25 Formas polimórficas de maleato de 5-[4-[2-[n-metil-n-(2-piridil) amino]etóxi]benzil]tiazolidina-2,4-diona e processo para a preparação das mesmas.
JP2002531121A JP2004509961A (ja) 2000-09-26 2001-09-25 ５−［４−［２−［ｎ−メチル−ｎ−（２−ピリジル）アミノ］エトキシ］ベンジル］チアゾリジン−２，４−ジオンマレイン酸塩の新規の多型形態およびそれらの調製方法
CA002426117A CA2426117A1 (fr) 2000-09-26 2001-09-25 Nouvelles formes polymorphes de 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate et procede de preparation associe
MXPA03002580A MXPA03002580A (es) 2000-09-26 2001-09-25 Nuevas formas polimorficas de maleato de 5-(4-(2-(n-metil-n-(2-piridil) amino)etoxi)bencil) tiazolidin-2, 4-diona y proceso para su preparacion.
SK375-2003A SK3752003A3 (sk) 2000-09-26 2001-09-25 Polymorfné formy 5-[4[2-[N-metyl-N-(2- pyridyl)aminol]etoxy]benzyl]tiazolidín-2,4-dión maleátu a spôsob ich prípravy
EP01971336A EP1322647A1 (fr) 2000-09-26 2001-09-25 Nouvelles formes polymorphes de 5- 4- 2- n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate et procede de preparation associe
AU2001291232A AU2001291232B8 (en) 2000-09-26 2001-09-25 Novel polymorphic forms of 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate and process for their preparation
AU9123201A AU9123201A (en) 2000-09-26 2001-09-25 Novel polymorphic forms of 5-(4-(2-(N-methyl-N-(2-pyridyl)amino)ethoxy)benzyl) thiazolidine-2,4-dione maleate and process for their preparation
IL155036A IL155036A (en) 2000-09-26 2003-03-23 Polymorphic forms of 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione maleate and pharmaceutical compositions containing the same
NO20031356A NO324968B1 (no) 2000-09-26 2003-03-25 Nye polymorfe former av 5-[4-[2-[N-metyl-N-(2-pyridyl]amino]etoksy]benzyl]tiazolidin-2,4-dionmaleat, fremgangsmate for fremstilling av samme, anvendelser av disse samt medikamenter inneholdende forbindelsene

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US6664278B2 (en) 1997-12-16 2003-12-16 Smithkline Beecham P.L.C. Hydrate of 5-[4-[2-(N-methyl-N-(2-pyridil)amino)ethoxy]benzyl]thiazolidine-2,4-dione maleic acid salt
WO2004062667A1 (fr) * 2003-01-08 2004-07-29 Dr. Reddy's Laboratories Limited Forme amorphe du maleate de rosiglitazone et procede de preparation
WO2004085435A1 (fr) * 2003-03-28 2004-10-07 Glaxo Group Limited Procede de preparation d'un polymorphe de maleate de rosiglitazone
US6806280B1 (en) 1999-04-23 2004-10-19 Smithkline Beecham P.L.C. Polymorph of 5-[4-[2-(n-methyl-n(2-pyridyl)amino)ethoxy]benzyl]-thiazolidine-2,4-dione, maleic acid salt
EP1468997A2 (fr) * 2003-04-18 2004-10-20 CHEMI S.p.A. Formes polymorphes de maléate de rosiglitatone
US6815457B1 (en) 1999-04-23 2004-11-09 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic
GB2405403A (en) * 2003-08-29 2005-03-02 Cipla Ltd Rosiglitazone maleate of particular polymorphic forms and methods of preparing rosiglitazone free base
WO2005095390A2 (fr) * 2004-03-31 2005-10-13 Sandoz Ag Nouveau co-precipite
WO2006010653A1 (fr) * 2004-07-28 2006-02-02 Chemi Spa Nouvelle forme polymorphe de maleate de rosiglitazone
WO2006010345A1 (fr) * 2004-07-27 2006-02-02 Zentiva, A.S. Sel d'acide oxalique avec 5-[4-[2-n-methyl-n-(2-pyridyl)-amino)ethoxy]benzyl]thiazolidin-2,4-dione, et procede de preparation et d'utilisation
JP2007504248A (ja) * 2003-09-04 2007-03-01 セルジーン・コーポレーション ３−（４−アミノ−１−オキソ−１，３ジヒドロ−イソインドール−２−イル）−ピペリジン−２，６−ジオンの多形相
US7230109B2 (en) 1997-12-16 2007-06-12 Smithkline Beecham P.L.C. 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione, maleic acid salt, hydrate as pharmaceutical
JP2007522172A (ja) * 2004-02-13 2007-08-09 サンド・アクチエンゲゼルシヤフト リン酸ロシグリタゾン及び多形体形態
CZ298424B6 (cs) * 2005-05-24 2007-09-26 Zentiva, A. S. Zpusob krystalizace rosiglitazonu a jeho derivátuze smesných rozpouštedel
US7358366B2 (en) 1999-04-23 2008-04-15 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic
US7368574B2 (en) 1997-12-16 2008-05-06 Smithkline Beecham P.L.C. Substituted thiazolidinedione derivative, process for its preparation and its pharmaceutical use
EP2184055A1 (fr) 2008-11-07 2010-05-12 LEK Pharmaceuticals d.d. Procédé de préparation de formes galéniques solides de maléate de rosiglitazone

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KR20070011497A (ko) * 2004-05-11 2007-01-24 산텐 세이야꾸 가부시키가이샤 각결막 장해 치료제
JP2005350451A (ja) * 2004-05-11 2005-12-22 Santen Pharmaceut Co Ltd 角結膜障害治療剤

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US7230109B2 (en) 1997-12-16 2007-06-12 Smithkline Beecham P.L.C. 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione, maleic acid salt, hydrate as pharmaceutical
US6664278B2 (en) 1997-12-16 2003-12-16 Smithkline Beecham P.L.C. Hydrate of 5-[4-[2-(N-methyl-N-(2-pyridil)amino)ethoxy]benzyl]thiazolidine-2,4-dione maleic acid salt
US7368574B2 (en) 1997-12-16 2008-05-06 Smithkline Beecham P.L.C. Substituted thiazolidinedione derivative, process for its preparation and its pharmaceutical use
US6806280B1 (en) 1999-04-23 2004-10-19 Smithkline Beecham P.L.C. Polymorph of 5-[4-[2-(n-methyl-n(2-pyridyl)amino)ethoxy]benzyl]-thiazolidine-2,4-dione, maleic acid salt
US6815457B1 (en) 1999-04-23 2004-11-09 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic
US7358366B2 (en) 1999-04-23 2008-04-15 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic
WO2004062667A1 (fr) * 2003-01-08 2004-07-29 Dr. Reddy's Laboratories Limited Forme amorphe du maleate de rosiglitazone et procede de preparation
WO2004085435A1 (fr) * 2003-03-28 2004-10-07 Glaxo Group Limited Procede de preparation d'un polymorphe de maleate de rosiglitazone
EA009331B1 (ru) * 2003-03-28 2007-12-28 Глэксо Груп Лимитед Способ получения полиморфа малеата розиглитазона
EP1468997A2 (fr) * 2003-04-18 2004-10-20 CHEMI S.p.A. Formes polymorphes de maléate de rosiglitatone
EP1468997A3 (fr) * 2003-04-18 2004-11-03 CHEMI S.p.A. Formes polymorphes de maléate de rosiglitatone
AU2004268816B2 (en) * 2003-08-29 2011-04-14 Cipla Limited Process for the production of polymorphs of rosiglitazone maleate
WO2005021541A3 (fr) * 2003-08-29 2005-05-06 Cipla Ltd Processus
KR101145433B1 (ko) * 2003-08-29 2012-05-16 씨아이피엘에이 엘티디. 로시글리타존 말레이트의 다형을 제조하는 방법
GB2421504A (en) * 2003-08-29 2006-06-28 Cipla Ltd Process for the production of polymorphs of rosiglitazone maleate
GB2405403A (en) * 2003-08-29 2005-03-02 Cipla Ltd Rosiglitazone maleate of particular polymorphic forms and methods of preparing rosiglitazone free base
US7678916B2 (en) 2003-08-29 2010-03-16 Cipla Limited Process
GB2421504B (en) * 2003-08-29 2008-12-03 Cipla Ltd Process for the production of polymorphs of rosiglitazone maleate
WO2005021541A2 (fr) * 2003-08-29 2005-03-10 Cipla Limited Processus
US8143286B2 (en) 2003-09-04 2012-03-27 Celgene Corporation Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione)
US9365538B2 (en) 2003-09-04 2016-06-14 Celgene Corporation Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
US11655232B2 (en) 2003-09-04 2023-05-23 Celgene Corporation Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
US11136306B2 (en) 2003-09-04 2021-10-05 Celgene Corporation Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-peridine-2,6-dione
US10590104B2 (en) 2003-09-04 2020-03-17 Celgene Corporation Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
JP4733037B2 (ja) * 2003-09-04 2011-07-27 セルジーン コーポレイション ３−（４−アミノ−１−オキソ−１，３ジヒドロ−イソインドール−２−イル）−ピペリジン−２，６−ジオンの多形相
US7977357B2 (en) 2003-09-04 2011-07-12 Celgene Corporation Polymorphic forms of 3-(4-amino-1-oxo-1, 3 dihydro-isoindo1-2-yl)-piperidine-2,6-dione
US7855217B2 (en) 2003-09-04 2010-12-21 Celgene Corporation Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
JP2007504248A (ja) * 2003-09-04 2007-03-01 セルジーン・コーポレーション ３−（４−アミノ−１−オキソ−１，３ジヒドロ−イソインドール−２−イル）−ピペリジン−２，６−ジオンの多形相
JP2007522172A (ja) * 2004-02-13 2007-08-09 サンド・アクチエンゲゼルシヤフト リン酸ロシグリタゾン及び多形体形態
WO2005095390A3 (fr) * 2004-03-31 2005-11-10 Sandoz Ag Nouveau co-precipite
WO2005095390A2 (fr) * 2004-03-31 2005-10-13 Sandoz Ag Nouveau co-precipite
WO2006010345A1 (fr) * 2004-07-27 2006-02-02 Zentiva, A.S. Sel d'acide oxalique avec 5-[4-[2-n-methyl-n-(2-pyridyl)-amino)ethoxy]benzyl]thiazolidin-2,4-dione, et procede de preparation et d'utilisation
EA010317B1 (ru) * 2004-07-27 2008-08-29 Зентива А.С. Соль щавелевой кислоты с 5-[4-[2-(n-метил-n-(2-пиридил)амино)этокси]бензил]тиазолидин-2,4-дионом, способ её получения и применение
WO2006010653A1 (fr) * 2004-07-28 2006-02-02 Chemi Spa Nouvelle forme polymorphe de maleate de rosiglitazone
CZ298424B6 (cs) * 2005-05-24 2007-09-26 Zentiva, A. S. Zpusob krystalizace rosiglitazonu a jeho derivátuze smesných rozpouštedel
EP2184055A1 (fr) 2008-11-07 2010-05-12 LEK Pharmaceuticals d.d. Procédé de préparation de formes galéniques solides de maléate de rosiglitazone

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CZ2003864A3 (cs) 2004-01-14
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AU9123201A (en) 2002-04-08
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NO20031356L (no) 2003-05-26
JP2004509961A (ja) 2004-04-02
HUP0301161A3 (en) 2005-04-28
NZ525498A (en) 2004-11-26
PL360661A1 (en) 2004-09-20
SK3752003A3 (sk) 2005-03-04
IL155036A0 (en) 2003-10-31
HUP0301161A2 (hu) 2003-11-28

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