DE2521905A1 - FUMARIC SALT OF 1-DIAETHYLAMINO-AETHYL-3-(P-METHOXYBENZYL)-1,2-DIHYDRO-QUINOXALIN-2-ONE, PROCESS FOR ITS PREPARATION AND PHARMACEUTICALS CONTAINING THIS COMPOUND - Google Patents

FUMARIC SALT OF 1-DIAETHYLAMINO-AETHYL-3-(P-METHOXYBENZYL)-1,2-DIHYDRO-QUINOXALIN-2-ONE, PROCESS FOR ITS PREPARATION AND PHARMACEUTICALS CONTAINING THIS COMPOUND

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Publication number
DE2521905A1
DE2521905A1 DE19752521905 DE2521905A DE2521905A1 DE 2521905 A1 DE2521905 A1 DE 2521905A1 DE 19752521905 DE19752521905 DE 19752521905 DE 2521905 A DE2521905 A DE 2521905A DE 2521905 A1 DE2521905 A1 DE 2521905A1
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Germany
Prior art keywords
methoxybenzyl
dihydro
quinoxalin
preparation
compound
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Granted
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DE19752521905
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German (de)
Other versions
DE2521905C2 (en
Inventor
Max Hoeriger
Josef Olaf Widauer
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Medichemie AG
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Medichemie AG
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Publication of DE2521905A1 publication Critical patent/DE2521905A1/en
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Publication of DE2521905C2 publication Critical patent/DE2521905C2/en
Expired legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

"Fumarsäuresalζ des l-Diäthylamino-äthyl-3-(p-methoxybenzyl)-l,2-dihydro-chinoxalin-2-ons, Verfahren zu seiner Herstellung und diese Verbindung enthaltende Arzneimittel""Fumaric acid sal des l-diethylamino-ethyl-3- (p-methoxybenzyl) -l, 2-dihydro-quinoxalin-2-one, Process for its preparation and medicinal products containing this compound "

Priorität: 21. Mai 1972K - Schweiz - Nummer 6957/72I-Priority: May 21, 197 2 K - Switzerland - number 6957/7 2 I-

In der CH-PS 513 884 ist die Herstellung von 1-Diäthylamino-äthyl-3-(p-methoxybenzyl)-l,2-dihydro-chinoxalin-2-on (Spasmium), in Form seiner Base vom Schmelzpunkt 69°C beschrieben. Diese Base, die wertvolle therapeutische Eigenschaften besitzt, weist den Nachteil einer gewissen Unbeständigkeit auf, vor allem ist sie gegen Licht und Wärme empfindlich. Sie ist außerdem in Wasser so gut wie unlöslich. Um in Wasser lösliche Salze herzustellen, wurde ihr Chlorhydrat synthetisiert, das aber noch weniger beständig als die Base ist.In CH-PS 513 884 the production of 1-diethylamino-ethyl-3- (p-methoxybenzyl) -l, 2-dihydro-quinoxalin-2-one (Spasmium), described in the form of its base with a melting point of 69 ° C. This base, which has valuable therapeutic properties, has the disadvantage of a certain instability, above all it is sensitive to light and heat. It is also practically insoluble in water. In order to produce water-soluble salts, its hydrochloride is synthesized, but it is even less stable than the base.

Aufgabe bei vorliegender Erfindung war es daher, Verbindungen des Spasmiums aufzufinden, die leichter löslich als die bekannten Salze sind.The object of the present invention was therefore to find compounds of the spasm which are more soluble than the known ones Salts are.

509849/0980509849/0980

Es wurde gefunden, daß das Fumarsäuresalz des Spasmiums leichter löslich und auch beständiger als die bisher bekanntgewordenen Salze ist.It has been found that the fumaric acid salt of the spasm is easier is soluble and also more stable than the previously known salts.

Gegenstand der Erfindung ist daher das Fumarsäuresalz des l-Diäthylamino-äthyl-3-(p-methoxybenzyl)-l,2-dihydro-chinoxalin-2-ons. The invention therefore relates to the fumaric acid salt of l-diethylamino-ethyl-3- (p-methoxybenzyl) -l, 2-dihydro-quinoxalin-2-one.

Des weiteren bildet einen Gegenstand vorliegender Erfindung ein Verfahren zur Herstellung des vorgenannten Fumar.säuresalzes, dasThe present invention also provides a process for the preparation of the aforementioned fumaric acid salt, which

man
dadurch gekennzeichnet ist, daß/ l-Diäthylarnino-äthyl-3-(p-methoxybenzyl)-l,2-dihydro-chinoxalin-2-on mit einer äquimolaren Menge Fumarsäure in einem organischen Lösungsmittel umsetzt. Bevorzugte Lösungsmittel sind niedermolekulare aliphatische Alkohole, insbesondere Methanol, Äthanol und Propanol.man
is characterized in that / l-diethylamino-ethyl-3- (p-methoxybenzyl) -l, 2-dihydro-quinoxalin-2-one is reacted with an equimolar amount of fumaric acid in an organic solvent. Preferred solvents are low molecular weight aliphatic alcohols, in particular methanol, ethanol and propanol.

Im pharmakologischen Spasmolysemodell ist das Fumarat der Base zumindest gleichwertig. Ein Trend zur besseren Wirkung des Fümarates bei Gabe von äquimolaren Dosen ist vorhanden. Außerdem zeigt Spasmium-Fumarat ausgeprägte Effekte auf die Cerebralgefäße bzw. die cerebrale Durchblutung im Sinne einer arteriellen Gefäßerweiterung und Durchblutungssteigerung. Solche Effekte wurden bisher weder mit Spasmium-Base noch mit anderen Spasmium-Salzen experimentell nachgewiesen.In the pharmacological spasmolysis model, the fumarate is at least equivalent to the base. A trend towards better effectiveness of the Fümarate is present when given equimolar doses. In addition, spasmic fumarate has pronounced effects on the cerebral vessels or the cerebral blood flow in the sense of arterial vasodilation and increased blood flow. Such effects have not been proven experimentally with either Spasmium Base or other Spasmium salts.

Aus diesem Grunde sind auch Arzneimittel mit einem Gehalt an dem Fumarsäuresalz des l-Diäthylamino-äthyl-3-(p-methoxybenzyl)-l,2-dihydro-chinoxalin-2-ons ein weiterer Gegenstand vorliegenderFor this reason, medicinal products containing the fumaric acid salt of l-diethylamino-ethyl-3- (p-methoxybenzyl) -l, 2-dihydro-quinoxalin-2-one are also used another subject matter at hand

S09849/0980S09849 / 0980

Erfindung. Gegebenenfalls können diese Arzneimittel weiterhin übliche Trägerstoffe, Verdünnungsmittel und/oder andere auf dem genannten Anwendungsgebiet gebräuchliche Wirkstoffe oder andere verträgliche, zur Behebung eventueller Nebenwirkungen bekannte Wirkstoffe enthalten.Invention. If necessary, these medicaments can also contain customary carriers, diluents and / or others mentioned field of application common active ingredients or other compatible, known for eliminating possible side effects Contain active ingredients.

Das Beispiel erläutert die Erfindung.The example illustrates the invention.

Beispielexample

36,5 g (0,1 Mol Spasmium-Base werden bei 45 bis 500C in 100 ml Äthanol gelöst. Zu dieser Lösung gibt man 11,6 g (0,1 Mol) Fumarsäure. Anstelle von Äthanol kann man auch Methanol oder Propanol verwenden.36.5 g (0.1 mol Spasmium base are dissolved at 45 to 50 0 C in 100 ml ethanol. To this solution is added 11.6 g (0.1 mol) of fumaric acid. In place of ethanol or methanol also can be Use propanol.

Die entstandene klare Lösung wird unter Rühren abgekühlt, wobei das Spasmium-Fumarat in feinkristalliner Form ausfällt. Der Niederschlag wird abfiltriert und mit kaltem Äthanol gewaschen. Man erhält eine Ausbeute von etwa 90 Prozent der Theorie. Das so erhaltene Spasmium-Fumarat besitzt einen Schmelzpunkt von 155 bis 157°C, ist leicht gelb gefärbt und ist in kaltem Wasser wenig, in Methanol und Äthanol etwas besser und in warmem Wasser sehr leicht löslich. Es kann aus diesen Lösungsmitteln umkristallisiert werden.The resulting clear solution is cooled while stirring, the spasmium fumarate precipitating in a finely crystalline form. The precipitation is filtered off and washed with cold ethanol. A yield of about 90 percent of theory is obtained. The thus obtained Spasmium fumarate has a melting point of 155 to 157 ° C, is slightly yellow in color and is little in cold water, somewhat better in methanol and ethanol and very easily soluble in warm water. It can be recrystallized from these solvents will.

Die vergleichende Untersuchung über die Haltbarkeit von Spasmium-Base, -Hydrochlorid und -Fumarat wurde wie folgt durchgeführt:The comparative study of the shelf life of Spasmium Base, - Hydrochloride and fumarate was carried out as follows:

509849/0 980 509849/0 980

VersuchsanordnungExperimental set-up

2prozentige Lösungen von Spasmiurn-Base, -Hydrochlorid und -Pumarat in Methanol wurden bei 300C + 0,10C mit UV-Licht bestrahlt (UV-Tauchlampe Marke Original Hanau, Typ PL j568). Der Gehalt der Lösungen wurde periodisch mit Hilfe der quantitativen Dünnschichtchromatographie bestimmt.2 per cent solutions of Spasmiurn base, hydrochloride and -Pumarat in methanol at 30 0 C + 0.1 0 C with UV-light irradiated (UV immersion lamp brand Original Hanau, type PL J568). The content of the solutions was determined periodically with the aid of quantitative thin-layer chromatography.

BestrahlungszeitExposure time
bei 30°Cat 30 ° C % unveränderte Spasmium-Verbindung
Base Hydrochlorid Fumarat % Spasmium connection unchanged
Base hydrochloride fumarate 98,3898.38 99,3299.32 1 Stunde1 hour 99,0099.00 97,4697.46 99,3299.32 2 Stunden2 hours 98,8598.85 96,4296.42 99,3299.32 3 Stunden3 hours 98,5298.52 93,6393.63 97,6297.62 5 Stunden5 hours 97,2897.28 92,4892.48 96,2296.22 . 7 Stunden. 7 hours 95,6495.64 88,3988.39 95,5395.53 9 Stunden9 hours 93,9393.93 86,0086.00 94,7494.74 12 Stunden12 hours 92,7092.70 80,9380.93 93,9093.90 16 Stunden16 hours 91,0891.08 63,8963.89 88,1488.14 33 Stunden33 hours 81,1981.19 58,1058.10 85,3085.30 36 Stunden36 hours 79,9079.90 56,3056.30 83,6583.65 39 Stunden39 hours 76,7376.73

509849/0980509849/0980

Claims (4)

- Patentansprüche- claims 1. Fumarsäuresalζ des l-Diäthylamino-äthyl-3-(p-methoxybenzyl)· 1,2-dihydro-chinoxalin-2-ons.1. Fumaric acid sal of l-diethylamino-ethyl-3- (p-methoxybenzyl) 1,2-dihydro-quinoxalin-2-one. 2. Verfahren zur Herstellung der Verbindung nach Anspruch 1, dadurch gekennz.ei chne t, daß man die freie Base l-Diäthylamino-äthyl-5-(p-methoxybenzyl)-li2-dihydro-chinbxalin-2-on mit einer äquimolaren Menge Fumarsäure in einem organischen Lösungsmittel umsetzt.2. Process for the preparation of the compound according to claim 1, characterized gekennz.ei chne t that the free base l-diethylamino-ethyl-5- (p-methoxybenzyl) -l i 2-dihydro-quinbxalin-2-one with a Reacts equimolar amount of fumaric acid in an organic solvent. 3. Verfahren nach Anspruch 2, dadurch gekennzeichnet, daß man als Lösungsmittel Methanol, Äthanol oder Propanol verwendet.3. The method according to claim 2, characterized in that one used as solvents methanol, ethanol or propanol. 4. ■ Arzneimittel, gekennzeichnet durch einen Gehalt an der Verbindung des Anspruches 1.4. ■ Medicines, characterized by a content of the Connection of claim 1. 509849/0980509849/0980
DE2521905A 1974-05-21 1975-05-16 Medicines to promote cerebral blood flow Expired DE2521905C2 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH695774A CH592637A5 (en) 1974-05-21 1974-05-21

Publications (2)

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DE2521905A1 true DE2521905A1 (en) 1975-12-04
DE2521905C2 DE2521905C2 (en) 1986-06-26

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DE2521905A Expired DE2521905C2 (en) 1974-05-21 1975-05-16 Medicines to promote cerebral blood flow

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JP (1) JPS5642599B2 (en)
AT (1) AT342059B (en)
AU (1) AU8114475A (en)
BE (1) BE829085A (en)
CA (1) CA1037477A (en)
CH (1) CH592637A5 (en)
DE (1) DE2521905C2 (en)
DK (1) DK138420B (en)
ES (1) ES437774A1 (en)
FR (1) FR2272087B1 (en)
GB (1) GB1461558A (en)
NL (1) NL7505715A (en)
SE (1) SE414634B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0032564A1 (en) * 1979-12-28 1981-07-29 Medichemie Ag Pharmaceutical use of caroverine and/or salts of caroverine, as well as salts of caroverine with xanthine acid remainders and nicotinic acid remainder
AT408837B (en) * 1998-06-19 2002-03-25 Phafag Ag USE OF CAROVERIN AND / OR CAROVERIN. HYDROCHLORIDE FOR THE PRODUCTION OF COMPOSITIONS THAT WORK AS AN ANTIOXIDANTS AND / OR OF NEUROREGENERATIVE COMPOSITIONS

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6115033U (en) * 1984-07-04 1986-01-28 石川島播磨重工業株式会社 Gas venting device in pressure vessel

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1189552B (en) * 1959-07-03 1965-03-25 Donau Pharmazie Ges M B H Process for the preparation of 2-oxo-1, 2-dihydroquinoxalines and their salts and quaternary ammonium compounds

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH513884A (en) * 1967-10-23 1971-10-15 Donau Pharmazie Gmbh Process for the preparation of tetrahydro-quinoxalin-2-ones

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1189552B (en) * 1959-07-03 1965-03-25 Donau Pharmazie Ges M B H Process for the preparation of 2-oxo-1, 2-dihydroquinoxalines and their salts and quaternary ammonium compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Helwig, B.: Moderne Arzneimittel, 1972, S. 936-939 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0032564A1 (en) * 1979-12-28 1981-07-29 Medichemie Ag Pharmaceutical use of caroverine and/or salts of caroverine, as well as salts of caroverine with xanthine acid remainders and nicotinic acid remainder
AT408837B (en) * 1998-06-19 2002-03-25 Phafag Ag USE OF CAROVERIN AND / OR CAROVERIN. HYDROCHLORIDE FOR THE PRODUCTION OF COMPOSITIONS THAT WORK AS AN ANTIOXIDANTS AND / OR OF NEUROREGENERATIVE COMPOSITIONS
US6573265B2 (en) 1998-06-19 2003-06-03 Phafag Aktiengesellschaft Use of 1-(aminoalkyl)-3-quinoxaline-2-on derivatives for the preparation of compounds having an antioxidant action

Also Published As

Publication number Publication date
SE414634B (en) 1980-08-11
JPS50160417A (en) 1975-12-25
DK138420C (en) 1978-09-04
FR2272087A1 (en) 1975-12-19
CH592637A5 (en) 1977-10-31
DE2521905C2 (en) 1986-06-26
AT342059B (en) 1978-03-10
ATA368375A (en) 1977-07-15
FR2272087B1 (en) 1979-06-22
GB1461558A (en) 1977-01-13
NL7505715A (en) 1975-11-25
BE829085A (en) 1975-09-01
DK138420B (en) 1978-09-04
CA1037477A (en) 1978-08-29
SE7505555L (en) 1975-11-24
JPS5642599B2 (en) 1981-10-06
ES437774A1 (en) 1977-01-16
AU8114475A (en) 1976-11-18
DK220675A (en) 1975-11-22

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