DE1035155B - Process for the preparation of therapeutically useful salts of 4,6-dioxyisophthalic acid - Google Patents
Process for the preparation of therapeutically useful salts of 4,6-dioxyisophthalic acidInfo
- Publication number
- DE1035155B DE1035155B DEF22415A DEF0022415A DE1035155B DE 1035155 B DE1035155 B DE 1035155B DE F22415 A DEF22415 A DE F22415A DE F0022415 A DEF0022415 A DE F0022415A DE 1035155 B DE1035155 B DE 1035155B
- Authority
- DE
- Germany
- Prior art keywords
- acid
- dioxyisophthalic
- preparation
- therapeutically useful
- salts
- 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.)
- Pending
Links
- 239000002253 acid Substances 0.000 title claims description 23
- 150000003839 salts Chemical class 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 210000004209 hair Anatomy 0.000 claims 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 150000002336 glycosamine derivatives Chemical class 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 229960003506 piperazine hexahydrate Drugs 0.000 description 1
- AVRVZRUEXIEGMP-UHFFFAOYSA-N piperazine;hexahydrate Chemical compound O.O.O.O.O.O.C1CNCCN1 AVRVZRUEXIEGMP-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
- C07C65/03—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring
- C07C65/05—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring o-Hydroxy carboxylic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von therapeutisch verwendbaren Salzen der 4,6-Dioxyisophthalsäure Die 4,6-Dioxyisophthalsäure ist bekannt. Zur Herstellung dieser Verbindung eignet sich z. B. das Verfahren von M. Pant litschka und H. Benger (Monatshefte für Chemie, 81, 293 [1950j). Eine pharmakologische oder andere medizinfsche bzw. biiochemische Untersuchung dieser Verbindung ist noch nicht bekanntgeworden. Process for the preparation of therapeutically useful salts of 4,6-Dioxyisophthalic acid 4,6-Dioxyisophthalic acid is known. For the production this connection is suitable for. B. the method of M. Pant litschka and H. Benger (Monthly books for chemistry, 81, 293 [1950j). A pharmacological or other medicinal product or biiochemical investigation of this compound is not yet known.
Es wurde nun überraschenderweise gefunden. daß man therapeutisch verwendbare Salze der 4,6-Dioxyisophthalsäure mit guter antiarthritischer und antiartheriosklerotischer Wirkung bei ausgezeichneter Verträglichkeit erhält. wenn man auf 4,6-Dioxyisophthalsäure, gegebenenfalls in Gegenwart eines Lösungs- oder Verdünnungsmittels, eine nicht toxische organische Base einwirken läßt. It has now been found, surprisingly. that one is therapeutic Usable salts of 4,6-dioxyisophthalic acid with good antiarthritic and antiartheriosclerotic Effect with excellent tolerance. if you rely on 4,6-dioxyisophthalic acid, optionally in the presence of a solvent or diluent, a non-toxic one allows organic base to act.
Die4,6-Dioxyisophthalsäure selbst besitzt zwar auch schon eine günstige pharmakologische Wirkung bei geringer Toxizität, jedoch ist sie als relativ starke organische Säure schlecht magenverträglich. Die Alkalisalze dieser Säure besitzen zwar diese unangenehme Wirkung nicht, haben jedoch den Nachteil, daß bei ihrer längeren Anwendung dem Körper heträchtliche Mengen NaH-- oder K+-1onen zugeführt würden. was bei den zu behandelnden chronischen Stoffwechselerkrankungen unvorteilhaft wäre. The 4,6-dioxyisophthalic acid itself already has a favorable one pharmacological effect with low toxicity, however, it is considered to be relatively strong organic acid poorly tolerated by the stomach. The alkali salts of this acid possess although not this unpleasant effect, but have the disadvantage that with their longer Application the body would supply considerable amounts of NaH-- or K + -1 ions. which would be disadvantageous for the chronic metabolic diseases to be treated.
Alle diese Nachteile können vermieden werden wenn man die Salze der 4,6-Dioxyisophthalsäure mit nicht toxischen organischen Basen verwendet. Diese zeigeil bei sehr guter Wirkung eine ausgezeichnete Verträglichkeit. Darüber hinaus haben sie z. B. den Vorteil einer verzögerten Ausscheidung. Dies bedeutet. daß ein therapeutisch wirksamer Blutspiegel fieber eine längere Zeit eingehalten wird. All of these disadvantages can be avoided by using the salts of the 4,6-Dioxyisophthalic acid used with non-toxic organic bases. This shows excellent tolerability with very good effect. In addition, have she z. B. the advantage of delayed elimination. This means. that a therapeutic effective blood level fever is maintained for a longer period of time.
Als nicht toxische Basen eignen sich insbesondere die Alkanolamine, wie Äthanolamin, Diäthanolamin, Aminozuckerderivate, wie Glukosamin. Methvlglukamin, oder cyclische Basen, wie Morpholin. Piperazin. The alkanolamines are particularly suitable as non-toxic bases, such as ethanolamine, diethanolamine, amino sugar derivatives such as glucosamine. Methglucamine, or cyclic bases such as morpholine. Piperazine.
Die Herstellung der Salze milt der 4.6-Dioxyisophthalsäure erfolgt entweder durch inniges Vermischen der Komponenten, gegebenenfalls in Gegenwart eines Lösungs- oder Verdünnungsmittels oder durch doppelte Umsetzung eines Salzes der A,6-Dioxvisophthalsäure mit Salzen der Basen. Als Lösungsmittel wählt man vorteilhaft ein solches, aus dem das Salz auch umkristallisiert werden kann.The salts are prepared using 4,6-dioxyisophthalic acid either by intimately mixing the components, optionally in the presence of one Solvent or diluent or by double reaction of a salt of A, 6-Dioxvisophthalic acid with salts of the bases. The solvent chosen is advantageous one from which the salt can also be recrystallized.
Man verwendet bevorzugt 2 Mol einer monobasischen oder 1 Mol einer dihasischen Verbindung auf 1 Mol der 4,6-Dioxyisophthalsäure. Man kann aber auch Salze aus 1 Mol Base und 1 Mol A,6-Dioxyisophthalsäure herstellen; diese haben jedoch den Nachteil. in wäß riger Lösung freie 4,6-Dioxyi sophthal säure abzuscheiden. It is preferred to use 2 moles of a monobasic or 1 mole of a monobasic dihasic compound to 1 mole of 4,6-dioxyisophthalic acid. But you can too Prepare salts from 1 mole of base and 1 mole of A, 6-dioxyisophthalic acid; however, these have the disadvantage. Separate out free 4,6-Dioxyi sophthalic acid in aqueous solution.
In allen Fällen erhält man Ausbeuten von 80 bis 90 0/o, bezogen auf eingesetzte 4,6-Dioxyisophthalsäure. In all cases, yields of 80 to 90%, based on 4,6-dioxyisophthalic acid used.
Beispiel 1 19,8 g 4,6-Dioxyisophthalsäure und 24 g Diäthanolamin werden am Wasserbad unter Rühren geschmolzen. Nach dem Umkristallisieren aus Isopropanol schmilzt das Bis-diäthanolaminsalz der 4,6-Dioxyisophthalsäure bei 1080 C. Example 1 19.8 g of 4,6-dioxyisophthalic acid and 24 g of diethanolamine are melted in a water bath while stirring. After recrystallization from isopropanol The bis-diethanolamine salt of 4,6-dioxyisophthalic acid melts at 1080 C.
Beispiel 2 19,8 g 4,6-Dioxyisophthalsäure werden in 400 ccm Alkohol suspendiert. mit 18 g Morpholin versetzt und zum Sieden erhitzt. Man filtriert heiß ab und läßt kristallisieren. Das so gewonnene Di-morpholinat der 4,6-Dioxyisophthalsäure schmilzt bei 1930 C unter Zersetzung. Example 2 19.8 g of 4,6-dioxyisophthalic acid are dissolved in 400 cc of alcohol suspended. mixed with 18 g of morpholine and heated to the boil. It is filtered hot and lets crystallize. The dimorpholinate of 4,6-dioxyisophthalic acid obtained in this way melts at 1930 C with decomposition.
Beispiel 3 19.8 g 4,6-Dioxyisophthalsäure werden in 50ccm Alkohol suspendiert und mit einer Lösung von 6,3 g Äthylendiamin in 150 ccm Wasser versetzt. Man erhitzt zum Sieden, filtriert ab und läßt kristallisieren. Example 3 19.8 g of 4,6-dioxyisophthalic acid are dissolved in 50 cc of alcohol suspended and treated with a solution of 6.3 g of ethylenediamine in 150 ccm of water. The mixture is heated to the boil, filtered off and allowed to crystallize.
Das so erhaltende Äthylendiaminsalz der 4,6-Dioxyisophthaisäure schmilzt hei 2280 C unter Zersetzung.The ethylenediamine salt of 4,6-dioxyisophthalic acid obtained in this way melts at 2280 C with decomposition.
Beispiel 4 19,8 g 4,6-Dioxyisophthalsäure werden in 50 ccm Alkohol suspendiert und mit einer Lösung von 20 g Piperazinhexahydrat in 50 ccm Wasser versetzt. Man löst heiß und läßt dann das Piperazinsalz der 4,6-Dioxyisophthalsäure auskristallisieren. Es schmilzt bei 2140 C unter Zersetzung. Example 4 19.8 g of 4,6-dioxyisophthalic acid are dissolved in 50 cc of alcohol suspended and treated with a solution of 20 g of piperazine hexahydrate in 50 ccm of water. The solution is hot and then the piperazine salt of 4,6-dioxyisophthalic acid is allowed to crystallize out. It melts at 2140 C with decomposition.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF22415A DE1035155B (en) | 1957-02-22 | 1957-02-22 | Process for the preparation of therapeutically useful salts of 4,6-dioxyisophthalic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF22415A DE1035155B (en) | 1957-02-22 | 1957-02-22 | Process for the preparation of therapeutically useful salts of 4,6-dioxyisophthalic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1035155B true DE1035155B (en) | 1958-07-31 |
Family
ID=7090434
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEF22415A Pending DE1035155B (en) | 1957-02-22 | 1957-02-22 | Process for the preparation of therapeutically useful salts of 4,6-dioxyisophthalic acid |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1035155B (en) |
-
1957
- 1957-02-22 DE DEF22415A patent/DE1035155B/en active Pending
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