DE1100642B - Process for the preparation of basic substituted alkylxanthine derivatives - Google Patents
Process for the preparation of basic substituted alkylxanthine derivativesInfo
- Publication number
- DE1100642B DE1100642B DEC15044A DEC0015044A DE1100642B DE 1100642 B DE1100642 B DE 1100642B DE C15044 A DEC15044 A DE C15044A DE C0015044 A DEC0015044 A DE C0015044A DE 1100642 B DE1100642 B DE 1100642B
- Authority
- DE
- Germany
- Prior art keywords
- derivatives
- alkylxanthine
- basic substituted
- preparation
- theophylline
- 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
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
- C07D473/08—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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von basisch substituierten Alkylxanthinderivaten Zusatz zur Patentanmeldung C13726IVb/12p (Auslegesdlrift 1 095 285) Gegenstand der Patentanmeldung C 13726 IVb/12p ist ein Verfahren zur Herstellung von basisch substituierten Alkylxanthinderivaten durch Umsetzung von 1- bzw. Process for the preparation of basic substituted alkylxanthine derivatives Addition to patent application C13726IVb / 12p (Auslegesdlrift 1 095 285) subject of Patent application C 13726 IVb / 12p is a process for the production of basic substituted Alkylxanthine derivatives by reacting 1- resp.
7-Halogenalkyl-3,7- bzw. -1,3-dimethylxanthinen mit primären Oxyalkylaminen bei höheren Temperaturen.7-haloalkyl-3,7- or -1,3-dimethylxanthines with primary oxyalkylamines at higher temperatures.
Es wurde nun gefunden, daß man auf analogem Wege durch Umsetzung von 1- bzw. 7-Halogenalkyl-3,7- bzw. It has now been found that you can use an analogous route by implementation of 1- or 7-haloalkyl-3,7- or
-1,3-dimethylxanthinen mit aliphatischen Diaminen, bei denen gegebenenfalls eine Aminogruppe alkyliert oder als Morpholinorest ausgebildet sein kann, zu Aminoalkyl aminoalkyl-xanthinen gelangt.-1,3-dimethylxanthines with aliphatic diamines, in which optionally an amino group can be alkylated or formed as a morpholino radical, to aminoalkyl aminoalkyl-xanthines arrives.
Die erhaltenen Verbindungen zeichnen sich durch therapeutisch wertvolle Eigenschaften bei geringer Giftigkeit aus, und sie unterscheiden sich von den bekannten tertiären Basen der Xanthine beispielsweise in folgenden Eigenschaften: Die an Mäusen bestimmte LD50 des 7-(ß-Aminoäthylß' - aminoäthyl) - theophyllin - dihydrochlorids beträgt 1215 mg/kg. Demgegenüber liegt z. B. beim 7-(Diäthylß-aminoäthyl)-theophyllin-hydrochlorid die LD50 bei nur 182 mg/kg. Die koronarerweiternde Wirkung ist bei beiden Substanzen gleich groß, das 7-(ß-Aminoäthylß'-aminoäthyl) -theophyllin-dihydrochlorid erhöht jedoch den Blutdruck leicht, wie in Versuchen an Meerschweinchen und Katzen festgestellt wurde, während die genannte Vergleichssubstanz den Blutdruck deutlich senkt. The compounds obtained are characterized by therapeutically valuable Properties with low toxicity, and they differ from the known tertiary bases of the xanthines, for example, in the following properties: Those on mice certain LD50 of 7- (ß-Aminoäthylß '- aminoethyl) - theophylline - dihydrochloride is 1215 mg / kg. In contrast, z. B. with 7- (diethylß-aminoethyl) -theophylline hydrochloride the LD50 is only 182 mg / kg. The coronary dilatation effect is with both substances the same size, the 7- (ß-Aminoäthylß'-aminoäthyl) -theophylline dihydrochloride increases however, the blood pressure slightly, as found in experiments on guinea pigs and cats while the comparison substance mentioned lowers blood pressure significantly.
Diese Wirkung des 7- (ß-Aminoäthyl-fl'-amino äthyl) -theophyllinsalzes kann für die therapeutische Verwendung als besonders wertvoll angesehen werden.This effect of the 7- (ß-aminoethyl-fl'-amino ethyl) -theophylline salt can be considered particularly valuable for therapeutic use.
Beispiel 1 Eine Mischung aus 30 g Äthylendiamin, 24,2 g 7-(ß-Chloräthyl)-theophyllin und 50 ccm absolutem Äthylalkohol wird unter Rühren 5 Stunden auf 1200 C erhitzt. Nun wird das Lösungsmittel abdestilliert und der Rückstand im Vakuum-Trockenschrank getrocknet. Man kocht das trockene Produkt mit absolutem Äthylalkohol aus, filtriert und säuert mit ätherischer Salzsäure an, wobei das rohe 7-(ß-Aminoäthyl-ß'-aminoäthyl)-theophyllin-dihydrochlorid ausfällt. Man reinigt durch Aufkochen mit Methanol. Aus den alkoholischen Filtraten erhält man weitere Mengen durch Einengen. Die Ausbeute beträgt 15 g; F. = 264 bis 271"C. Example 1 A mixture of 30 g of ethylenediamine, 24.2 g of 7- (ß-chloroethyl) -theophylline and 50 cc of absolute ethyl alcohol is heated to 1200 C for 5 hours while stirring. The solvent is then distilled off and the residue in a vacuum drying cabinet dried. The dry product is boiled with absolute ethyl alcohol and filtered and acidified with ethereal hydrochloric acid, the crude 7- (ß-aminoethyl-ß'-aminoethyl) theophylline dihydrochloride fails. Purify by boiling with methanol. From the alcoholic filtrates one obtains further amounts by concentration. The yield is 15 g; F. = 264 to 271 "C.
Beispiel 2 24,25 g 7-(P-Chloräthyl)-theophyllin, 51 g y-Dimethylamino-propylamin und 50 ccm Äthylalkohol werden 5 Stunden unter Rühren und Rückfluß gekocht. Anschließend dampft man im Vakuum ein, suspendiert den Rückstand in absolutem Äthylalkohol, säuert mit alkoholischer Salzsäure an und saugt nach 2 Stunden ab. Example 2 24.25 g of 7- (P-chloroethyl) -theophylline, 51 g of γ-dimethylamino-propylamine and 50 cc of ethyl alcohol are boiled for 5 hours with stirring and reflux. Afterward it is evaporated in vacuo, the residue is suspended in absolute ethyl alcohol, acidified with alcoholic hydrochloric acid and sucks off after 2 hours.
Das getrocknete Produkt wird zweimal mit absolutem Methylalkohol aufgekocht, nach dem Erkalten abgesaugt und getrocknet. Es werden so 30,8 g 7-(y-Dimethyl- aminopropyl - ß' - aminoäthyl) - theophyllin - hydrochlorid vom Schmelzpunkt 288 bis 290"C erhalten.The dried product is boiled twice with absolute methyl alcohol, vacuumed and dried after cooling. 30.8 g of 7- (y-dimethyl- aminopropyl - β '- aminoethyl) - theophylline hydrochloride with a melting point of 288 to 290 "C.
Beispiel 3 12,12 g l-(ß-Chloräthyl)-theobromin und 31,5 g N-(y-Aminopropyl)-morpholin werden in 25 ccm absolutem Äthylalkohol 4 Stunden unter Rühren und Rückfluß gekocht. Man destilliert den Alkohol und das überschüssige Aminopropyl-morpholin im Vakuum ab und neutralisiert die alkoholische Lösung des Rückstandes mit alkoholischer Salzsäure. Zur Ausfällung des Hydrochlorids tropft man unter Rühren in absoluten Äther ein. Das rohe Salz wird schnell abgesaugt und im Vakuumexsikkator getrocknet. Zur Reinigung wird aus Isopropylalkohol und anschließend zweimal aus absolutem Methylalkohol umkristallisiert. Auf diese Weise werden 11 g l-(y-Morpholinopropyl-ß'-aminoäthyl)-theobromin-dihydrochlorid vom Schmelzpunkt 268 bis 2700 C erhalten. Example 3 12.12 g of l- (β-chloroethyl) theobromine and 31.5 g of N- (γ-aminopropyl) morpholine are boiled in 25 cc of absolute ethyl alcohol for 4 hours with stirring and reflux. The alcohol and the excess aminopropyl morpholine are distilled off in vacuo and neutralizes the alcoholic solution of the residue with alcoholic hydrochloric acid. To precipitate the hydrochloride, absolute ether is added dropwise with stirring. The raw salt is quickly sucked off and dried in a vacuum desiccator. For cleaning is recrystallized from isopropyl alcohol and then twice from absolute methyl alcohol. In this way, 11 g of l- (γ-morpholinopropyl-ß'-aminoethyl) -theobromine dihydrochloride obtained from melting point 268 to 2700 C.
Claims (1)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEC13726A DE1095285B (en) | 1956-09-25 | 1956-09-25 | Process for the preparation of basic substituted alkylxanthine derivatives |
| DEC13727A DE1100640B (en) | 1956-09-25 | 1956-09-25 | Process for the preparation of basic substituted alkylxanthine derivatives |
| DEC15043A DE1100641B (en) | 1956-09-25 | 1956-10-22 | Process for the preparation of basic substituted alkylxanthine derivatives |
| DEC15044A DE1100642B (en) | 1956-09-25 | 1957-06-22 | Process for the preparation of basic substituted alkylxanthine derivatives |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEC13726A DE1095285B (en) | 1956-09-25 | 1956-09-25 | Process for the preparation of basic substituted alkylxanthine derivatives |
| DEC15044A DE1100642B (en) | 1956-09-25 | 1957-06-22 | Process for the preparation of basic substituted alkylxanthine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1100642B true DE1100642B (en) | 1961-03-02 |
Family
ID=33098953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEC15044A Pending DE1100642B (en) | 1956-09-25 | 1957-06-22 | Process for the preparation of basic substituted alkylxanthine derivatives |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1100642B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1221641B (en) * | 1962-03-30 | 1966-07-28 | Degussa | Process for the preparation of basic substituted theophylline derivatives |
-
1957
- 1957-06-22 DE DEC15044A patent/DE1100642B/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1221641B (en) * | 1962-03-30 | 1966-07-28 | Degussa | Process for the preparation of basic substituted theophylline derivatives |
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