EP1756100A1 - Salt of phosphoric acid with 5-[4-[2-(n-methyl-n-(2-pyridyl)amino)-ethoxy] benzy] thiazolidin-2,4-dione and a method of its preparation - Google Patents
Salt of phosphoric acid with 5-[4-[2-(n-methyl-n-(2-pyridyl)amino)-ethoxy] benzy] thiazolidin-2,4-dione and a method of its preparationInfo
- Publication number
- EP1756100A1 EP1756100A1 EP05741667A EP05741667A EP1756100A1 EP 1756100 A1 EP1756100 A1 EP 1756100A1 EP 05741667 A EP05741667 A EP 05741667A EP 05741667 A EP05741667 A EP 05741667A EP 1756100 A1 EP1756100 A1 EP 1756100A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- salt
- phosphoric acid
- thiazolidin
- dione
- ethoxy
- 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.)
- Withdrawn
Links
- 150000003839 salts Chemical class 0.000 title claims abstract description 85
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 title claims abstract description 71
- 229910000147 aluminium phosphate Inorganic materials 0.000 title claims abstract description 33
- 238000000034 method Methods 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title claims description 8
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 title description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 title description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims abstract description 119
- 239000012453 solvate Substances 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 239000000243 solution Substances 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- 239000002245 particle Substances 0.000 claims description 13
- 229910019142 PO4 Inorganic materials 0.000 claims description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 11
- 239000010452 phosphate Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 238000005384 cross polarization magic-angle spinning Methods 0.000 claims description 5
- 238000002844 melting Methods 0.000 claims description 5
- 230000008018 melting Effects 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 230000002058 anti-hyperglycaemic effect Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 3
- 239000012535 impurity Substances 0.000 claims description 3
- 238000004482 13C cross polarization magic angle spinning Methods 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 238000002441 X-ray diffraction Methods 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- 229960004586 rosiglitazone Drugs 0.000 description 41
- 239000000126 substance Substances 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000012458 free base Substances 0.000 description 11
- 235000021317 phosphate Nutrition 0.000 description 11
- 238000009835 boiling Methods 0.000 description 8
- 238000000634 powder X-ray diffraction Methods 0.000 description 8
- 238000005259 measurement Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000001035 drying Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 238000009826 distribution Methods 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- 238000000113 differential scanning calorimetry Methods 0.000 description 4
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 4
- 229960004592 isopropanol Drugs 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 0.000 description 3
- 229960003271 rosiglitazone maleate Drugs 0.000 description 3
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- AWFYPPSBLUWMFQ-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=C2 AWFYPPSBLUWMFQ-UHFFFAOYSA-N 0.000 description 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000001875 carbon-13 cross-polarisation magic angle spinning nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical group [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- -1 ethyl acetate) Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- OZJSJUKQPIGBBO-UHFFFAOYSA-N n-methyl-n-[2-[4-(1,3-thiazolidin-5-ylmethyl)phenoxy]ethyl]pyridin-2-amine Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1CNCS1 OZJSJUKQPIGBBO-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 238000000722 phosphorus-31 cross-polarisation magic angle spinning nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- 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
Definitions
- the invention concerns a new salt of rosiglitazone, i.e. of 5-[4-[2-(N-methyl-N-(2- pyridyl)amino)-ethoxy]benzyl]thiazolidin-2,4-dione, with phosphoric acid (H 3 PO 4 ), including a method of its preparation and physical and chemical properties.
- the salt can be used to prepare pharmaceuticals for treatment of hyperglycemia in patients with diabetes mellitus of type 2.
- 2,4-dione of formula I is a known anti-hyperglycemic agent, which was first described in patent EP306228 (1989) of Beecham. Rosiglitazone is in praxis used in the form of salts, especially with maleic acid (WO 9405659 Al, formula II). Recently, a number of crystalline modifications of rosiglitazone maleate II and of its hydrates have been known (WO 2000064893 A2 and WO 2000064892 A2, WO 2002026737 Al, WO 9931095 Al, WO 9931094 Al and WO 9931093 Al). A number of other addition salts is also known, both with mineral acids and with strong organic acids (WO 0220519 Al, WO 0220518 Al).
- the solution being described comprises a new salt of rosiglitazone of formula I with phosphoric acid, which surprisingly shows a number of advantageous qualities that have not yet been observed in the above described salts.
- the invention concerns a salt of phosphoric acid with 5-[4-[2-(N-methyl-N-(2- pyridyl)amino)ethoxy]-benzyl]thiazolidin-2,4-dione, described by formula III, and a method of its preparation.
- the method allows preparing a hitherto undisclosed salt of rosiglitazone of formula I with phosphoric acid (H 3 PO 4 ) in high yield and quality required for pharmaceutical substances.
- our product is a salt that contains a component described by formula I and phosphoric acid (H 3 PO ) in the ratio 1:1, i.e. rosiglitazone dihydrogenphosphate.
- the chemical structure of the salt we have obtained can be described by formulae III, Ill-a, III- b and III-c, which are equivalent to each other. However, for the sake of simplicity, formula III will be used further on in the text. It can be assumed that the obtained salt shows anti- hyperglycemic activity as do other salts of rosiglitazone. An economically viable method of preparation of the salt has also been found, which can be used also on the production scale.
- the method of preparation according to the invention consists in a reaction of 5-[4-[2-(N- methyl-N-(2-pyridyl)-amino)ethoxy]benzyl]thiazolidin-2,4-dione of formula I with concentrated phosphoric acid or its solution, which is carried out in an organic solvent.
- the manufacture of the salt of formula III can be preferably carried out at a temperature close to the boiling point of the used solvent, where good solubility of the starting compound of formula I is ensured.
- the reaction itself can take place at a wide range of temperatures, including temperatures higher than the boiling point of the used solvent at atmospheric pressure. In order to ensure successful accomplishment of the reaction, one can chose reaction temperatures from the interval of 0 up to 150 °C.
- the process of preparation of the salt of formula III is described by the equation in Scheme 1. m Scheme 1
- the choice of the solvent depends on solubility of the starting substance and the product.
- Alcohols e.g. methanol, ethanol, 1-propanol, 2-propanol, butanols
- esters of carboxylic acids e.g. ethyl acetate
- ethers e.g. dioxane, tetrahydrofuran, diethyl ether
- ketones e.g. acetone, cyclohexanone
- acetonitrile their arbitrary mixtures and mixtures with water in any ratios can be used as solvents.
- An advantageous form of the salt of formula III is the crystalline form, which is chemically stable, chemically very pure (above 99.5% according to HPLC), well soluble in water and in aqueous solutions of hydrochloric acid, which can be prepared in high yields in the defined crystalline modification, and which is characterized by suitable particle size for further processing.
- the above-described crystalline salt of formula III is well soluble in water and in aqueous solutions of hydrochloric acid. Especially the solubility in solutions of hydrochloric acid is very important considering the acidobasic conditions in the digestive system (especially in the stomach). It offers indication of the solubility of the substance after it is digested, which is a very important factor for evaluating pharmaceutical effectiveness of the substance.
- a comparison of the solubility of the salt of formula III in acidic environment with that of several other rosiglitazone salts is documented in Example 7.
- Fig. 1 is the X-Ray powder diffraction of the crystalline salt of phosphoric acid with rosiglitazone (III) prepared according to Examples 1 and 2.
- Fig. 2 depicts the DSC curve of the crystalline salt of phosphoric acid with rosiglitazone (III) prepared according to Example 1.
- Fig. 3 depicts the DSC curve of an equimolar mixture of the crystalline salt of phosphoric acid with rosiglitazone (III) and the free base of rosiglitazone (I) prepared according to Example 3.
- Fig. 4 is the 13 C CP-MAS NMR spectrum of the crystalline salt of phosphoric acid with rosiglitazone (III) prepared according to Example 1.
- Fig. 5 is the 31 P CP-MAS NMR spectra of the crystalline salt of phosphoric acid with rosiglitazone (III) prepared according to Example 1.
- Fig. 6 is the FT-IR spectra of the crystalline salt of phosphoric acid with rosiglitazone (III) prepared according to Example 1.
- Fig. 7 depicts a diagram of distribution of particle sizes according to the maximum dimension
- EXAMPLE 4 10 g of the free base of rosiglitazone (I) was dissolved in 250 ml of boiling ethanol. To the obtained solution, a solution of 3.6 ml of concentrated phosphoric acid (85% H 3 PO 4 ) in 40 ml of ethanol was added. It was left to cool down f eely under stirring for 2.5 hours. After filtration, washing of the filtration cake with 30 ml of ethanol and drying in a vacuum drier, crystalline salt III was obtained, m.p. 173-175 °C. The yield was 93 %.
- ANALYTICAL DATA (A-G): The following analytical data clearly characterize the crystalline salt of rosiglitazone phosphate of chemical formula III.
- the melting points of crystalline salts of rosiglitazone phosphate III were measured at Kofler's block with the heating rate of the sample of 10 °C (up to 150 °C) and 4 °C (above 150 °C) per minute. The measured values of melting points range from 170 to 178 °C. Typical melting-point values are presented in Examples 1-6.
- the DSC recordings were measured using the instrument Perkin Elmer PYRIS 1. The measurements were performed for samples weighingt 3-5 mg. The samples were heated to temperatures 20-210 °C with the heating rate of 10 °C per minute. The measured DSC curves are presented in Figures 2 and 3. The crystalline salt of rosiglitazone phosphate III shows a maximum at the temperature 174 to 175 °C.
- the NMR spectra of the crystalline salt of rosiglitazone phosphate III for phosphorus isotope 31 P were measured using spectrometer Avance 500 Bruker with the measurement frequency 202.46 MHz using technique CP/MAS with sample rotation of 15 kHz. The obtained spectrum is presented in Figure 5. The location of the peak (chemical shift expressed in ppm relative to the ammonium phosphate signal) is: 2.0.
- the distribution of particle sizes was measured microscopically with automatic evaluation of the measurement.
- a diagram of distribution of particle sizes according to the maximum dimension (MaxFeret) is presented in Figure 7.
- the measurement has shown that the crystalline salt of rosiglitazone phosphate HI shows a distribution of particle sizes from 0 to 100 ⁇ m with the maximum in the interval of 0-10 ⁇ m (frequency of incidence about 68 %). More than 99 % of particles had its maximum dimension smaller than 50 ⁇ m.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CZ20040712A CZ296468B6 (cs) | 2004-06-10 | 2004-06-10 | Sul kyseliny fosforecné s 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidin-2,4-dionema zpusob její prípravy |
| PCT/CZ2005/000040 WO2005121136A1 (en) | 2004-06-10 | 2005-05-25 | Salt of phosphoric acid with 5-[4-[2-(n-methyl-n-(2-pyridyl)amino)-ethoxy] benzy] thiazolidin-2,4-dione and a method of its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1756100A1 true EP1756100A1 (en) | 2007-02-28 |
Family
ID=34981408
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP05741667A Withdrawn EP1756100A1 (en) | 2004-06-10 | 2005-05-25 | Salt of phosphoric acid with 5-[4-[2-(n-methyl-n-(2-pyridyl)amino)-ethoxy] benzy] thiazolidin-2,4-dione and a method of its preparation |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1756100A1 (cs) |
| CZ (1) | CZ296468B6 (cs) |
| EA (1) | EA010176B1 (cs) |
| UA (1) | UA87855C2 (cs) |
| WO (1) | WO2005121136A1 (cs) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE186724T1 (de) * | 1987-09-04 | 1999-12-15 | Beecham Group Plc | Substituierte thiazolidindionderivate |
| GB9218830D0 (en) * | 1992-09-05 | 1992-10-21 | Smithkline Beecham Plc | Novel compounds |
| GB9909041D0 (en) * | 1999-04-20 | 1999-06-16 | Smithkline Beecham Plc | Novel pharmaceutical |
| GB0129872D0 (en) * | 2001-12-13 | 2002-02-06 | Smithkline Beecham Plc | Novel pharmaceutical |
| AU2003269483A1 (en) * | 2003-09-10 | 2005-03-29 | Biocon Limited | Phosphoric acid salt of 5-((4-(2-(methyl-2-pyridinylamino) ethoxy) phenyl) methyl)- 2,4-thiazolidinedione |
| GB2410948A (en) * | 2004-02-13 | 2005-08-17 | Sandoz Ag | Novel phosphoric acid salt of rosiglitazone |
-
2004
- 2004-06-10 CZ CZ20040712A patent/CZ296468B6/cs not_active IP Right Cessation
-
2005
- 2005-05-25 EP EP05741667A patent/EP1756100A1/en not_active Withdrawn
- 2005-05-25 EA EA200700003A patent/EA010176B1/ru not_active IP Right Cessation
- 2005-05-25 UA UAA200700258A patent/UA87855C2/ru unknown
- 2005-05-25 WO PCT/CZ2005/000040 patent/WO2005121136A1/en active Application Filing
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2005121136A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| UA87855C2 (en) | 2009-08-25 |
| WO2005121136A1 (en) | 2005-12-22 |
| CZ296468B6 (cs) | 2006-03-15 |
| EA010176B1 (ru) | 2008-06-30 |
| CZ2004712A3 (cs) | 2006-01-11 |
| EA200700003A1 (ru) | 2007-04-27 |
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