DE862301C - Process for the preparation of readily water-soluble esters of 1, 3- or 3, 7-dimethylxanthine-8-acetic acid - Google Patents
Process for the preparation of readily water-soluble esters of 1, 3- or 3, 7-dimethylxanthine-8-acetic acidInfo
- Publication number
- DE862301C DE862301C DED10467A DED0010467A DE862301C DE 862301 C DE862301 C DE 862301C DE D10467 A DED10467 A DE D10467A DE D0010467 A DED0010467 A DE D0010467A DE 862301 C DE862301 C DE 862301C
- Authority
- DE
- Germany
- Prior art keywords
- dimethylxanthine
- acetic acid
- preparation
- readily water
- soluble esters
- 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.)
- Expired
Links
- 150000002148 esters Chemical class 0.000 title claims description 6
- UNYOWLZOZCPSKF-UHFFFAOYSA-N 2-(3,7-dimethyl-2,6-dioxopurin-8-yl)acetic acid Chemical compound CN1C(=O)NC(=O)C2=C1N=C(CC(O)=O)N2C UNYOWLZOZCPSKF-UHFFFAOYSA-N 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 2
- -1 diethylaminoethyl halide Chemical class 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims 1
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 10
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229960004559 theobromine Drugs 0.000 description 5
- 229960000278 theophylline Drugs 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- IVJJBZSMAAOYBS-UHFFFAOYSA-N C(C)(=O)O.CC1(N=C2NC(NC(C2=N1)=O)=O)C Chemical class C(C)(=O)O.CC1(N=C2NC(NC(C2=N1)=O)=O)C IVJJBZSMAAOYBS-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 229910021607 Silver chloride Inorganic materials 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 1
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 1
- CEUABESLRGJGPU-UHFFFAOYSA-N 3,7-dimethylpurine-2,6-dione silver Chemical compound [Ag].N1C(=O)N(C)C=2N=CN(C)C2C1=O CEUABESLRGJGPU-UHFFFAOYSA-N 0.000 description 1
- ZUYLZSGHROAYCD-UHFFFAOYSA-N acetic acid;3,7-dimethylpurine-2,6-dione Chemical compound CC(O)=O.CN1C(=O)NC(=O)C2=C1N=CN2C ZUYLZSGHROAYCD-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/10—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 3 and 7, e.g. theobromine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von leicht wasserlöslichen Estern der 1, 3- bzw. 3, 7-Dimethylxanthin-8-essigsäure Die vorliegende Erfindung betrifft die Herstellung der Dimethylaminoäthylester der i, 3- bzw. 3, 7-Dimethylxanthin-8-essigsäure (Theophyllin- und Theobrominessigsäure) sowie der Diäthylaminoäthylester der Theobromin- und Theophyllinessigsäure.Process for the preparation of readily water-soluble esters of 1, 3- or 3, 7-dimethylxanthine-8-acetic acid The present invention relates to Production of the dimethylaminoethyl ester of i, 3- or 3, 7-dimethylxanthine-8-acetic acid (Theophylline and theobromine acetic acid) and the diethylaminoethyl ester of theobromine and theophyllinetic acid.
Es wurde gefunden, daß man zu pharmakologisch wirksamen Substanzen gelangt, wenn man das Silber- i salz der Theophyllinessigsäure oder der Theobrominessigsäure mit einem Dimethylaminoäthyl- oder Diäthylaminoäthylhalogenid umsetzt. Man erhält Verbindungen, in denen die genannten substituierten Aminoalkoholreste esterartig an die oben beschriebenen Dimethylxanthinessigsäuren gebunden sind und die bisher noch nicht dargestellt wurden.It has been found that pharmacologically active substances can be obtained obtained when one uses the silver i salt of theophyllinetic acid or theobromineetic acid with a dimethylaminoethyl or diethylaminoethyl halide. You get Compounds in which the substituted amino alcohol radicals mentioned are ester-like are bound to the above-described dimethylxanthine acetic acids and the previously have not yet been displayed.
. Die auf Grund der obigen Reaktion erhaltenen Ester sind insofern interessante Verbindungen, als sie sehr leicht wasserlöslich sind und infolgedessen die Herstellung hochkonzentrierter wäßriger Lösungen des Theophyllins bzw. des Theobromins gestatten. Wichtig ist vor allem, daß die genannten Substanzen eine ausgesprochen spasmolytische Wirkung auf die glatte Muskulatur der Bronchien besitzen. Diese Eigenschaft kommt dem Theophyllin und Theobromin zu, deren diesbezüglicher Anwendung aber durch ihre geringe Löslichkeit im Wasser Grenzen gesetzt sind.. The esters obtained due to the above reaction are so far interesting compounds as they are very easily soluble in water and as a result the production of highly concentrated aqueous solutions of theophylline or theobromine allow. Above all, it is important that the substances mentioned have a pronounced effect Have a spasmolytic effect on the smooth muscles of the bronchi. This attribute comes to theophylline and theobromine, but their application in this regard through their low solubility in water are limited.
Die Verfahrensprodukte sind aber auch in anderer Hinsicht von besonderem Interesse. Die angewandten Dimethylxanthine-Essigsäureester wirken nicht nur als Lösungsvermittler für Theophyllin und Theobromin, sondern sind, wie der pharmakologische Versuch zeigt, auch ohne jegliche Nebenwirkung. Bemerkenswert ist, daß die Toxizität der Substanzen erheblich geringer ist als die des Theophyllins und Theobromins, so daß selbst Dosen von 5,0 g pro Kilogramm Maus gut und ohne Nebenerscheinungen vertragen wurden.However, the products of the process are also of particular interest in other respects. The applied dimethylxanthine acetic acid esters not only act as solubilizers for theophylline and theobromine, but are, as the pharmacological experiment shows, without any side effects. It is noteworthy that the toxicity of the substances is considerably lower than that of theophylline and theobromine, so that even doses of 5.0 g per kilogram of mouse were tolerated well and without side effects.
Beispiel i 3o,4 mg Dimethylaminoäthylchlorid werden in 26oo ccm Methanol gelöst und die Lösung wird unter Rühren mit ioo g theophyllinessigsaurem Silber versetzt. Nach 2stündigem--Erhitzen auf dem Wasser= bade unter Rückfluß und 'mechanischem Rühren wird vom ausgeschiedenen Chlorsilber abfiltriert. Das Filtrat dampft man bis zur Hälfte seines Volumens im. Vakuum ein und fällt den theophyllinessigsauren Dimethylaminoäthylesterl mit Äther aus. Nach dem Abtrennen des Lösungsmittels und Trocknen erhält man 61,o g des genannten Esters.. Schmelzpunkt 25o bis 253° unter Zersetzung.Example i 3o, 4 mg of dimethylaminoethyl chloride are dissolved in 26oo ccm of methanol dissolved and the solution is stirred with 100 g of theophyllinessigsaurem silver offset. After 2 hours - heating on the water = bathing under reflux and mechanical stirring is used to filter off the precipitated silver chloride. The filtrate one steams up to half of its volume in the. Vacuum and falls to the theophyllinetic acids Dimethylaminoäthylesterl with ether. After separating the solvent and Drying gives 61.0 g of the ester mentioned .. Melting point below 25o to 253 ° Decomposition.
4,920 mg Sbst.: g,215 mg C02; 2,72o mg' H20; 3,357 mg Sbst.: o,686 ccm N (25,5°, 722 mTn); C"H"04N5: berechnet C 50,4 H 6,15 N 22;6; gefunden C 50,54 H 6,1g N 22,5.4.920 mg Sbst .: g, 215 mg C02; 2.72o mg 'H20; 3.357 mg Sbst .: 0.686 cc N (25.5 °, 722 mTn); C "H" 04N5: calcd C 50.4 H 6.15 N 22; 6; found C 50.54, H 6.1 g, N 22.5.
Beispiel 2 -39,7 g Diäthylaminoäthylchlorid werden in 22oo ccm Methanol gelöst und die Lösung wird unter Rührenmit Zoo g theobrominessigsaurem Silber versetzt. Nach 2 ständigem --Erhitzen auf-- dem: Wasserbade unter Rückfluß und mechanischem Rühren wird vom ausgeschiedenen Chlorsilber abfiltriert. Das Filtrat dampft man bis zur Hälfte seines Volumens im Vakuum ein und fällt den theobrominessigsauren Diäthylaminoäthylester mit Äther aus. Nach dem Abtrennen des Lösungsmittels und Trocknen erhält man 46,o g des genannten Esters. Schmelzpunkt 236 bis 238° unter Zersetzung.Example 2 - 39.7 g of diethylaminoethyl chloride are dissolved in 22oo cc of methanol and the solution is mixed with zoo g of silver theobromine acid while stirring. After 2 hours of heating on the: water bath under reflux and mechanical stirring, the precipitated silver chloride is filtered off. The filtrate is evaporated to half of its volume in vacuo and the theobromine-acetic acid diethylaminoethyl ester is precipitated with ether. After separating off the solvent and drying, 46, og of the ester mentioned are obtained. Melting point 236 to 238 ° with decomposition.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DED10467A DE862301C (en) | 1951-10-23 | 1951-10-23 | Process for the preparation of readily water-soluble esters of 1, 3- or 3, 7-dimethylxanthine-8-acetic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DED10467A DE862301C (en) | 1951-10-23 | 1951-10-23 | Process for the preparation of readily water-soluble esters of 1, 3- or 3, 7-dimethylxanthine-8-acetic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE862301C true DE862301C (en) | 1953-01-08 |
Family
ID=7033292
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DED10467A Expired DE862301C (en) | 1951-10-23 | 1951-10-23 | Process for the preparation of readily water-soluble esters of 1, 3- or 3, 7-dimethylxanthine-8-acetic acid |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE862301C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1103932B (en) * | 1954-02-06 | 1961-04-06 | Andre Buzas Dr Ing | Process for the preparation of esters of 7-ª ‰ -oxyaethyltheophylline |
| DE1118204B (en) * | 1959-05-23 | 1961-11-30 | Krewel Leuffen Gmbh | Process for the preparation of basic theophyllinyl acetic acid esters |
-
1951
- 1951-10-23 DE DED10467A patent/DE862301C/en not_active Expired
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1103932B (en) * | 1954-02-06 | 1961-04-06 | Andre Buzas Dr Ing | Process for the preparation of esters of 7-ª ‰ -oxyaethyltheophylline |
| DE1118204B (en) * | 1959-05-23 | 1961-11-30 | Krewel Leuffen Gmbh | Process for the preparation of basic theophyllinyl acetic acid esters |
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