CH634066A5 - 4-(2-Thenoyl)-2,3-dichlorophenoxyacetic acid of the polymorphic modification B, a process for its preparation and its use - Google Patents
4-(2-Thenoyl)-2,3-dichlorophenoxyacetic acid of the polymorphic modification B, a process for its preparation and its use Download PDFInfo
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- CH634066A5 CH634066A5 CH1612877A CH1612877A CH634066A5 CH 634066 A5 CH634066 A5 CH 634066A5 CH 1612877 A CH1612877 A CH 1612877A CH 1612877 A CH1612877 A CH 1612877A CH 634066 A5 CH634066 A5 CH 634066A5
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- polymorphic modification
- dichlorophenoxyacetic acid
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- 230000004048 modification Effects 0.000 title claims description 43
- 238000012986 modification Methods 0.000 title claims description 43
- AGHANLSBXUWXTB-UHFFFAOYSA-N tienilic acid Chemical compound ClC1=C(Cl)C(OCC(=O)O)=CC=C1C(=O)C1=CC=CS1 AGHANLSBXUWXTB-UHFFFAOYSA-N 0.000 title claims description 14
- 238000000034 method Methods 0.000 title claims 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 10
- 238000010521 absorption reaction Methods 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 238000002329 infrared spectrum Methods 0.000 claims description 4
- 239000012454 non-polar solvent Substances 0.000 claims description 4
- 238000002844 melting Methods 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000003021 water soluble solvent Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 5
- 230000008018 melting Effects 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 229960000356 tienilic acid Drugs 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 2
- 238000004455 differential thermal analysis Methods 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- KRVKCQGNBBYQJK-MVNLRXSJSA-N (2r,3r,4r,5r)-hexane-1,2,3,4,5,6-hexol;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO KRVKCQGNBBYQJK-MVNLRXSJSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010591 solubility diagram Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 230000003424 uricosuric effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
-
- 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
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Die Erfindung betrifft die in den Ansprüchen gekennzeichneten Gegenstände. The invention relates to the objects characterized in the claims.
4-(2-Thenoyl)-2,3-dichlorphenoxyessigsäure, nachfolgend kurz Ticrynafen genannt, ist ein wertvoller Arzneistoff. Seine diuretischen, uricosuretischen und den Lipidspiegel senkenden Eigenschaften sind beschrieben in den US-PSen 3 758 506,3 958 004,3 969 508 und 3 969 529 und in Eur. J. Med. Chem.-Chimica. Therapeutica, Bd. 9 (6) (1974), S. 625 bis 633. 4- (2-Thenoyl) -2,3-dichlorophenoxyacetic acid, hereinafter referred to as Ticrynafen for short, is a valuable drug. Its diuretic, uricosuretic and lipid-lowering properties are described in US Pat. Nos. 3,758,506.3,958,004,3,969,508 and 3,969,529 and in Eur. J. Med. Chem. Chimica. Therapeutica, Vol. 9 (6) (1974), pp. 625 to 633.
Es wurde festgestellt, dass Ticrynafen in zwei polymorphen, kristallinen Modifikationen vorliegen kann. Die höherschmelzende polymorphe Modifikation wird nachfolgend mit A, die niedrigerschmelzende, metastabile polymorphe Modifikation mit B bezeichnet. Die polymorphen Modifikationen werden durch Untersuchung im polarisierten Licht und Thermomikroskopie, Röntgenbeugung an Pulver, Infrarotspektroskopie, Differentialthermoanalyse sowie ihre entsprechenden Löslichkeitsdiagramme, die Lös-lichkeitsmaxima, die Löslichkeitsgeschwindigkeiten und die Umwandlungstemperatur der Modifikation B in die Modifikation A gekennzeichnet. It was found that ticrynafen can exist in two polymorphic, crystalline modifications. The higher-melting polymorphic modification is referred to below as A, the lower-melting, metastable polymorphic modification as B. The polymorphic modifications are characterized by examination in polarized light and thermomicroscopy, X-ray diffraction on powder, infrared spectroscopy, differential thermal analysis as well as their corresponding solubility diagrams, the solubility maxima, the solubility rates and the transformation temperature of modification B into modification A.
Die polymorphe Modifikation A wird durch Umkristallisieren aus wässrigen und/oder in Wasser löslichen Lösungsmitteln, wie Aceton, Äthanol, Äthanol/Wasser und durch Aufschlämmen in Wasser erhalten. Sie bildet sich auch durch Kristallisation aus Chloroform oder Äthylendichlorid, jedoch ist die Kristallisationsgeschwindigkeit sehr niedrig. The polymorphic modification A is obtained by recrystallization from aqueous and / or water-soluble solvents such as acetone, ethanol, ethanol / water and by slurrying in water. It is also formed by crystallization from chloroform or ethylene dichloride, but the rate of crystallization is very slow.
Die metastabile polymorphe Modifikation B wird durch langsame oder schnelle Kristallisation, einschliesslich raschem Abkühlen, aus unpolaren Lösungsmitteln, wie Xylol, Toluol oder Benzol, erhalten. Auch beim raschen Umkristallisieren aus warmen Lösungen von Chloroform oder Äthylendichlorid wird die Modifikation B erhalten. The metastable polymorphic modification B is obtained by slow or rapid crystallization, including rapid cooling, from non-polar solvents such as xylene, toluene or benzene. Modification B is obtained even when rapidly recrystallizing from warm solutions of chloroform or ethylene dichloride.
Die polymorphe Modifikation B kann durch einstündiges Aufschlämmen der Kristalle in einer wässrigen Lösung bei 90 bis 100°C in die stabile Form A umgewandelt werden. Bei Temperaturen zwischen 20 und 24°C und unter Rühren erfolgt die Umwandlung der Modifikation B in die Modifikation A innerhalb 5 bis 7 Stunden. The polymorphic modification B can be converted into the stable form A by slurrying the crystals in an aqueous solution at 90 to 100 ° C. for one hour. At temperatures between 20 and 24 ° C and with stirring, the conversion of modification B into modification A takes place within 5 to 7 hours.
Die jeweilige Umwandlung der beiden Modifikationen ist in Tabelle I wiedergegeben. The respective conversion of the two modifications is shown in Table I.
Tabelle I Table I
Umwandlung der polymorphen Modifikationen des Ticrynafens durch Umkristallisieren aus verschiedenen Lösungsmitteln Conversion of the polymorphic modifications of ticrynafen by recrystallization from different solvents
Lösungsmittel Kristallisations- Polymorphe geschwindigkeit Modifikation Solvent crystallization polymorphic rate modification
Toluol rasch B Toluene rapidly B
Toluol langsam B Toluene slow B
Chloroform rasch B Chloroform rapidly B
Chloroform langsam A Chloroform slow A
Chloroform langsam unter A Chloroform slowly under A
Rühren stir
Äthylendichlorid rasch B Ethylene dichloride rapidly B
Äthylendichlorid langsam A Ethylene dichloride slow A
Äthylendichlorid langsam unter A Ethylene dichloride slowly under A
Rühren stir
Aceton langsam A Acetone slow A
Aceton rasch A 95prozentiges wässriges Acetone rapid A 95 percent aqueous
Äthanol rasch A Ethanol quickly A
Xylol rasch B Xylene Rapidly B
Benzol rasch B Benzene rapidly B
Somit wird bei der Herstellung von Ticrynafen je nach der Art des Umkristallisierens das Reaktionsprodukt in einer der polymorphen Modifikationen erhalten. Die Ergebnisse von Tabelle I zeigen deutlich, dass bei den in der vorstehenden Literatur angeführten Herstellungsverfahren die polymorphe Modifikation A des Ticrynafens erhalten wird. Die erfin-dungsgemässe polymorphe Modifikation B ist neu. Thus, the reaction product is obtained in one of the polymorphic modifications depending on the type of recrystallization in the production of Ticrynafen. The results of Table I clearly show that the polymorphic modification A of the ticrynafen is obtained in the production processes mentioned in the above literature. The polymorphic modification B according to the invention is new.
Beispiele für zur Herstellung der erfindungsgemässen polymorphen Modifikation B geeignete unpolare Lösungsmittel sind nichtchlorierte, aromatische Lösungsmittel, wie Benzol, Toluol oder Xylol. Examples of non-polar solvents suitable for producing the polymorphic modification B according to the invention are non-chlorinated, aromatic solvents, such as benzene, toluene or xylene.
Die Umwandlung der metastabilen polymorphen Modifikation B in die stabile Modifikation A erfolgt durch etwa 1 stündiges Aufschlämmen der Form B in Wasser bei 90 bis 100°C oder durch Umkristallisieren aus einem Gemisch von Aceton und Wasser oder durch Umkristallisieren aus Chloroform, Äthylendichlorid oder 95prozentigem wässrigem Äthanol. Bevorzugt ist das Umkristallisieren aus einem Gemisch von Aceton und Wasser, durch das man die reine A-Form erhält. The conversion of the metastable polymorphic modification B into the stable modification A takes place by slurrying the form B in water at 90 to 100 ° C. for about 1 hour or by recrystallization from a mixture of acetone and water or by recrystallization from chloroform, ethylene dichloride or 95 percent aqueous ethanol . Recrystallization from a mixture of acetone and water, by which the pure A form is obtained, is preferred.
Die Infrarotspektren der beiden polymorphen Modifikationen des Ticrynafens wurden in Paraffino! (Nujol) aufgenommen. Die Absorptionsbanden der beiden Modifikationen zeigen deutliche Unterschiede. Die polymorphe Modifikation A weist eine starke, spitze Doppel-Absorptionsbande bei 1768 und 1752 cm-1 und eine starke-, sehr spitze Absorptionsbande bei 1410 und 1180 cm-1 auf, während das Infrarotspektrum der polymorphen Modifikation B in diesen The infrared spectra of the two polymorphic modifications of Ticrynafen were recorded in Paraffino! (Nujol) added. The absorption bands of the two modifications show clear differences. The polymorphic modification A has a strong, pointed double absorption band at 1768 and 1752 cm-1 and a strong, very pointed absorption band at 1410 and 1180 cm-1, while the infrared spectrum of the polymorphic modification B in these
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634066 634066
Bereichen keine Absorptionsbanden zeigt. Die polymorphe Modifikation B weist starke Absorptionsbanden bei 1725 und 1418 cm-' und eine sehr schwache Absorptionsbande bei 1180 cm-' auf. Die beiden Infrarotspektren sind als Fig. 1 und Fig. 2 dieser Beschreibung beigefügt. Areas shows no absorption bands. The polymorphic modification B has strong absorption bands at 1725 and 1418 cm- 'and a very weak absorption band at 1180 cm-'. The two infrared spectra are attached to this description as FIGS. 1 and 2.
Die Differentialthermoanalyse der beiden polymorphen Modifikationen ergibt für die stabile Modifikation A einen höheren Fp. von 155°C als die metastabile Modifikation B mit einem Fp. von 152°C. The differential thermal analysis of the two polymorphic modifications shows a higher mp of 155 ° C. for the stable modification A than the metastable modification B with a mp of 152 ° C.
Lösungsversuche zeigen, dass die Modifikation B in Wasser bei verschiedenen Temperaturen leichter löslich ist als die Modifikation A. Attempted solutions show that modification B is more soluble in water at different temperatures than modification A.
Das Beispiel erläutert die Erfindung. The example explains the invention.
Beispiel example
Herstellung der polymorphen Modifikation B Production of the polymorphic modification B
1. Durch Umkristallisieren aus Äthylendichlorid 100 ml Äthylendichlorid werden unter Rühren und Erhitzen bis kurz unterhalb des Siedepunktes (ca. 80°C) innerhalb 2 bis 3 Minuten mit 25 g polymorpher Modifikation A von Ticrynafen in Mengen von 1 bis 2 g versetzt und weiter bei 80°C gehalten. Nach vollständiger Lösung wird noch weitere 1 bis 2 Minuten erhitzt. 1. By recrystallization from ethylene dichloride 100 ml of ethylene dichloride are added with stirring and heating to just below the boiling point (approx. 80 ° C.) within 2 to 3 minutes with 25 g of polymorphic modification A of ticrynafen in amounts of 1 to 2 g and further at Kept at 80 ° C. After complete dissolution, the mixture is heated for a further 1 to 2 minutes.
Das Reaktionsgefäss wird rasch in einem Bad von Trockeneis und Aceton gekühlt. Nach 5 bis 10 Minuten werden die ausgefällten Kristalle filtriert und an der Luft getrocknet. Die polymorphe Modifikation B von Ticrynafen wird in 84pro-zentiger Ausbeute erhalten. The reaction vessel is rapidly cooled in a bath of dry ice and acetone. After 5 to 10 minutes, the precipitated crystals are filtered and air-dried. The polymorphic modification B of Ticrynafen is obtained in 84 percent yield.
2. Durch Umkristallisieren aus unpolaren Lösungsmitteln 100 ml Benzol (Toluol oder Xylol) werden unter mässigem s Rühren und Erhitzen mit 8 bis 10 g der polymorphen Modifikation A von Ticrynafen in Mengen von etwa 1 g versetzt, bis die Lösung gesättigt ist. Die gesättigte Lösung wird weiter gerührt und erhitzt, wobei etwas ungelöster Feststoff verbleibt. Nachdem die Lösung vollständig gesättigt ist, werden io 10 ml Lösungsmittel zugegeben, und das Gemisch wird weiter bis zur vollständigen Lösung erhitzt, wobei nötigenfalls, um eine vollständige Lösung zu bewirken, noch Lösungsmittel in Mengen von jeweils 1 ml zugesetzt wird. 2. By recrystallization from non-polar solvents 100 ml of benzene (toluene or xylene) are mixed with moderate stirring and heating with 8 to 10 g of the polymorphic modification A of ticrynafen in amounts of about 1 g until the solution is saturated. The saturated solution is further stirred and heated, leaving some undissolved solid. After the solution is completely saturated, 10 ml of solvent are added and the mixture is further heated until it is completely dissolved, with solvent being added in amounts of 1 ml each to effect a complete solution.
Das Reaktionsgefäss wird in einem Eiswasserbad bis zur 15 Bildung von Kristallen gekühlt. Nach weiterem 10- bis 15minütigem Kühlen wird der Niederschlag abfiltriert und an der Luft getrocknet. Es wird die polymorphe Modifikation B von Ticrynafen in einer Ausbeute von 85 bis 90% erhalten. The reaction vessel is cooled in an ice water bath until crystals are formed. After cooling for a further 10 to 15 minutes, the precipitate is filtered off and air-dried. The polymorphic modification B of ticrynafen is obtained in a yield of 85 to 90%.
20 Die Wirkung der polymorphen Modifikation B von Ticrynafen als Diuretikum und Uricosurikum wurde an mit Phos-phat-Mannit infundierten Mongrel-Hunden untersucht. 20 The effect of the polymorphic modification B of Ticrynafen as a diuretic and uricosuric was investigated in mongrel dogs infused with phosphate-mannitol.
Nach intravenöser Verabreichung von 15 mg/kg der polymorphen Modifikation B und anschliessender Untersuchung 25 der Nierenclearance wurde eine Zunahme von ausgeschiedenen Natrium- und Kaliumionen sowie von Harnsäure beobachtet. After intravenous administration of 15 mg / kg of the polymorphic modification B and subsequent examination 25 of the kidney clearance, an increase in excreted sodium and potassium ions and in uric acid was observed.
1 Blatt Zeichnungen 1 sheet of drawings
Claims (6)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB56277 | 1977-01-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH634066A5 true CH634066A5 (en) | 1983-01-14 |
Family
ID=9706556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1612877A CH634066A5 (en) | 1977-01-07 | 1978-01-01 | 4-(2-Thenoyl)-2,3-dichlorophenoxyacetic acid of the polymorphic modification B, a process for its preparation and its use |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS5387349A (en) |
| AU (1) | AU510569B2 (en) |
| BE (1) | BE862688A (en) |
| CH (1) | CH634066A5 (en) |
| DD (1) | DD134096A5 (en) |
| DE (1) | DE2800489A1 (en) |
| DK (1) | DK565677A (en) |
| ES (1) | ES465181A1 (en) |
| FR (1) | FR2376856A1 (en) |
| GR (1) | GR66062B (en) |
| IL (1) | IL53651A0 (en) |
| IT (1) | IT1089800B (en) |
| LU (1) | LU78823A1 (en) |
| NL (1) | NL7800213A (en) |
| PL (1) | PL203865A1 (en) |
| PT (1) | PT67416B (en) |
| SE (1) | SE7714959L (en) |
| ZA (1) | ZA777531B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2184411C (en) * | 1995-01-04 | 2004-05-11 | Rafael Foguet Ambros | Process for preparing polymorphs b and c of 1-[2,4-dichloro-.beta.-[(7-chlorobenzo[b]thien-3-yl)methoxy]phenethyl]imidazole mononitrate |
| US20070122483A1 (en) * | 2005-11-29 | 2007-05-31 | Sharon Myers | Fluocinolone acetonide drug substance polymorphic interconversion |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2115042A2 (en) * | 1970-11-25 | 1972-07-07 | Cerpha | 4-2-thienylketo-2,3-dichlorophenoxy acetic acid - prepn and purificn |
-
1977
- 1977-12-16 PT PT67416A patent/PT67416B/en unknown
- 1977-12-17 ES ES465181A patent/ES465181A1/en not_active Expired
- 1977-12-19 AU AU31698/77A patent/AU510569B2/en not_active Expired
- 1977-12-19 DK DK565677A patent/DK565677A/en not_active Application Discontinuation
- 1977-12-19 ZA ZA00777531A patent/ZA777531B/en unknown
- 1977-12-20 IL IL53651A patent/IL53651A0/en unknown
- 1977-12-23 IT IT31205/77A patent/IT1089800B/en active
- 1977-12-26 JP JP15718977A patent/JPS5387349A/en active Pending
- 1977-12-30 SE SE7714959A patent/SE7714959L/en not_active Application Discontinuation
-
1978
- 1978-01-01 CH CH1612877A patent/CH634066A5/en not_active IP Right Cessation
- 1978-01-02 FR FR7800007A patent/FR2376856A1/en active Granted
- 1978-01-04 GR GR55095A patent/GR66062B/el unknown
- 1978-01-04 DD DD78203100A patent/DD134096A5/en unknown
- 1978-01-05 DE DE19782800489 patent/DE2800489A1/en not_active Withdrawn
- 1978-01-06 NL NL7800213A patent/NL7800213A/en not_active Application Discontinuation
- 1978-01-06 LU LU78823A patent/LU78823A1/en unknown
- 1978-01-06 BE BE184139A patent/BE862688A/en not_active IP Right Cessation
- 1978-08-06 PL PL20386578A patent/PL203865A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| LU78823A1 (en) | 1978-06-09 |
| JPS5387349A (en) | 1978-08-01 |
| ZA777531B (en) | 1978-10-25 |
| AU510569B2 (en) | 1980-07-03 |
| DE2800489A1 (en) | 1978-07-13 |
| IT1089800B (en) | 1985-06-18 |
| FR2376856A1 (en) | 1978-08-04 |
| NL7800213A (en) | 1978-07-11 |
| FR2376856B1 (en) | 1981-01-23 |
| DD134096A5 (en) | 1979-02-07 |
| IL53651A0 (en) | 1978-03-10 |
| PL203865A1 (en) | 1979-06-04 |
| DK565677A (en) | 1978-07-08 |
| SE7714959L (en) | 1978-07-08 |
| AU3169877A (en) | 1979-06-28 |
| PT67416A (en) | 1978-01-01 |
| GR66062B (en) | 1981-01-15 |
| BE862688A (en) | 1978-07-06 |
| PT67416B (en) | 1979-05-22 |
| ES465181A1 (en) | 1979-01-01 |
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