DE1620193B - Optically active and racemic 2,3-dimethoxy-10-acetylamino-berbin and a process for their preparation. Eliminated from: 1620172 - Google Patents
Optically active and racemic 2,3-dimethoxy-10-acetylamino-berbin and a process for their preparation. Eliminated from: 1620172Info
- Publication number
- DE1620193B DE1620193B DE1620193B DE 1620193 B DE1620193 B DE 1620193B DE 1620193 B DE1620193 B DE 1620193B
- Authority
- DE
- Germany
- Prior art keywords
- dimethoxy
- berbin
- acetylamino
- racemic
- optically active
- 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
- OVOYKRXKKUBPQE-UHFFFAOYSA-N n-(2,3-dimethoxy-6,8,13,13a-tetrahydro-5h-isoquinolino[2,1-b]isoquinolin-10-yl)acetamide Chemical compound C1C2=CC(NC(C)=O)=CC=C2CC2N1CCC1=C2C=C(OC)C(OC)=C1 OVOYKRXKKUBPQE-UHFFFAOYSA-N 0.000 title claims description 8
- 238000000034 method Methods 0.000 title description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- XJHCQHMARGLDCB-UHFFFAOYSA-N 2,3-dimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinolin-10-amine Chemical compound COC1=CC=2C3CC4=CC=C(C=C4CN3CCC2C=C1OC)N XJHCQHMARGLDCB-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 229940125725 tranquilizer Drugs 0.000 description 3
- 239000003204 tranquilizing agent Substances 0.000 description 3
- 230000002936 tranquilizing effect Effects 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- AEQDJSLRWYMAQI-UHFFFAOYSA-N Tetrahydropalmatine Natural products C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- AEQDJSLRWYMAQI-KRWDZBQOSA-N tetrahydropalmatine Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3C[C@H]2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-KRWDZBQOSA-N 0.000 description 2
- OPTJHLICZXOBIQ-UHFFFAOYSA-N 2,3-dimethoxy-6,8,13,13a-tetrahydro-5h-isoquinolino[2,1-b]isoquinoline Chemical class C1C2=CC=CC=C2CC2N1CCC1=C2C=C(OC)C(OC)=C1 OPTJHLICZXOBIQ-UHFFFAOYSA-N 0.000 description 1
- 206010001022 Acute psychosis Diseases 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010010305 Confusional state Diseases 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 239000007799 cork Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
Description
CO-CH,CO-CH,
2. Verfahren zur Herstellung der Verbindungen gemäß Anspruch 1, dadurch gekennzeichnet, daß man in an sich bekannter Weise 2,3-Dimethoxy-10-amino-berbin mit Essigsäureanhydrid in Gegenwart von Pyridin umsetzt.2. Process for the preparation of the compounds according to claim 1, characterized in that 2,3-dimethoxy-10-aminoberbin is used in a manner known per se with acetic anhydride in the presence of pyridine.
3. Arzneimittel, bestehend aus einer Verbindung gemäß Anspruch 1 als Wirkstoff und üblichen Hilfs- und Trägerstoffen.3. Medicaments consisting of a compound according to claim 1 as an active ingredient and usual Auxiliary and carrier materials.
Die Erfindung betrifft optisch aktives und racemisches 2,3-Dimethoxy-10-acetylamino-berbin der Formel The invention relates to optically active and racemic 2,3-dimethoxy-10-acetylamino-berbin of the formula
CH,OCH, O
CH, OCH, O
1. Tranquilizerwirkung1. Tranquilizer effect
Sie wird mit dem Test der schiefen Ebene bestimmt. Man verwendet eine Korkplatte, die zur Horizontalebene in einem Winkel von 70° angeordnet ist und nahe ihrem oberen Rand eine horizontal befestigte Metalleiste aufweist. Eine normale Maus, die etwa 15 cm unterhalb der Leiste auf die Platte gesetzt wurde, klettert nach kurzer Eingewöhnungszeit auf der geneigten Fläche nach oben bis zu der Leiste, wo sie eine Ruhestellung erreicht.It is determined with the inclined plane test. A cork board is used which is arranged at an angle of 70 ° to the horizontal plane and has a horizontally attached metal strip near its upper edge. A normal mouse that's about 15 cm below the bar, climbs on the plate after a short period of getting used to inclined surface up to the bar, where it reaches a rest position.
Die Tiere werden 15 Minuten, 30 Minuten, 45 Minuten, 1 Stunde, I1I2 Stunden und 2 Stunden, 2V2 Stunden, 3 Stunden, 3V2 Stunden und 4 Stunden nach der Verabreichung des zu untersuchenden Produkts getestet, und bei jeder Dosis wird die Anzahl der Mäuse festgestellt, die nicht hinaufklettern.Animals are tested 15 minutes, 30 minutes, 45 minutes, 1 hour, I 1 I 2 hours and 2 hours, 2V 2 hours, 3 hours, 3V 2 hours and 4 hours after administration of the test product, and at each dose the number of mice that do not climb up is determined.
Die Produkte werden auf intraperitonealem Weg in saurer Lösung an Gruppen von 5 Mäusen in verschiedenen Dosen verabreicht. Die maximale Wirkung wird zwischen 45 Minuten und I1/2 Stunden erzielt.The products are administered intraperitoneally in acidic solution to groups of 5 mice in various doses. The maximum effect is achieved between 45 minutes and 1 1/2 hours.
Die graphische Darstellung der erhaltenen maximalen Wirkung, gemessen in Prozent der Mäuse, die nicht hinaufklettern, in Abhängigkeit von dem Logarithmus der Dosen, gestattet die Bestimmung der Dosis (DP50), die bei 50% der Versuchstiere die maximale Wirkung hervorruft.The graph of the maximum effect obtained, measured as a percentage of the mice that did not climb, as a function of the logarithm of the doses, allows the dose (DP 50 ) to be determined which produces the maximum effect in 50% of the test animals.
2. Bestimmung der Toxizität2. Determination of toxicity
Die Bewertung der Toxizität wurde bei Mäusen vom Rocklandstamm durchgeführt, die zwischen 18 und 22 g wogen. Das erfindungsgemäße Produkt wurde auf intraperitonealem Weg an Gruppen von Mäusen in steigenden Dosen verabreicht. Die Tiere werden während einer Woche unter Beobachtung gehalten.The toxicity assessment was carried out on mice from the Rockland strain that were between Weighed 18 and 22 g. The product according to the invention was administered intraperitoneally to groups of Administered to mice in increasing doses. The animals are observed for one week held.
Die nachstehende Tabelle faßt die erhaltenen Resul-The table below summarizes the results obtained
täte zusammen.would do together.
CO-CH,CO-CH,
40 2,3-Dimethoxy-10-acethylamino- 40 2,3-dimethoxy-10-acethylamino
berbin berbin
TetrahydropalmatinTetrahydropalmatine
DP50 DP 50
mg/kgmg / kg
10
2010
20th
DL50 DL 50
mg/kgmg / kg
DL50/DPS( DL 50 / DP S (
75
10075
100
7,5
57.5
5
ein Verfahren zu deren Herstellung und Arzneimittel, die aus einer der genannten Verbindungen als Wirkstoff und üblichen Hilfs- und Trägerstoffen bestehen.a process for their production and pharmaceuticals made from one of the compounds mentioned as an active ingredient and usual auxiliary and carrier materials.
Diese Verbindungen zeichnen sich durch wertvolle Tranquilizer- und analgetische Eigenschaften aus.These compounds are characterized by valuable tranquilizer and analgesic properties.
Sie können verwendet werden zur Behandlung von manischer Erregung, akuten Psychosen, Syndromen der Confusio mentalis, Ubererregbarkeit, Unruhe und Angstzuständen, funktionellen organischen Störungen, die durch psychische Anspannung hervorgerufen oder verstärkt werden, Neuralgien und verschiedenen Schmerzen.They can be used to treat manic arousal, acute psychosis, syndromes the mental confusion, over-excitability, restlessness and anxiety, functional organic disorders, caused or intensified by psychological tension, neuralgia and various Pains.
Die 2,3-Dimethoxy-berbinverbindungen der allgemeinen Formel I werden buccal, transkutan oder rektal angewandt.The 2,3-dimethoxy-berbin compounds of the general formula I are buccal, transcutaneous or applied rectally.
Das erfindungsgemäße 2,3-Dimethoxy-lO-acetylamino-berbin wurde hinsichtlich der Tranquilizerwirkung mit der bekannten Verbindung Tetrahydropalmatin unter Berücksichtigung der Toxizitäten verglichen. The 2,3-dimethoxy-10-acetylamino-berbin according to the invention became with the well-known compound tetrahydropalmatine with regard to the tranquilizer effect compared taking into account the toxicities.
Die erfindungsgemäßen 2,3-Dimethoxy-lO-acetylamino-berbine werden dadurch hergestellt, daß man in an sich bekannter Weise ein 2,3-Dimethoxy-10-amino-berbin mit Essigsäureanhydrid in Gegenwart von Pyridin umsetzt.The 2,3-dimethoxy-10-acetylamino-berbine according to the invention are prepared by adding a 2,3-dimethoxy-10-amino-berbin in a manner known per se with acetic anhydride in the presence of pyridine.
Das als Ausgangssubstanz benötigte 2,3-Dimethoxy-10-amino-berbin und seine Herstellung sind in der deutschen Offenlegungsschrift 1 620 193 angeführt. Das folgende Beispiel erläutert die Erfindung.The 2,3-dimethoxy-10-amino-berbin required as the starting substance and its production are listed in German Offenlegungsschrift 1,620,193. The following example illustrates the invention.
Herstellung desManufacture of the
2,3-Dimethoxy-lO-acetylamino-berbins2,3-Dimethoxy-10-acetylamino-berbins
Man suspendiert 2,5 g 2,3-Dimethoxy-10-aminoberbin in 3,75 ecm Pyridin, fügt 2,5 ecm Essigsäureanhydrid zu und hält die Temperatur unter 300C mit Hilfe eines Wasserbads. Es bildet sich eine kristalline Masse, die man bei Zimmertemperatur bis zur vollständigen Lösung mit Wasser versetzt und durch Zugabe von Triäthylamin neutralisiert. Man saugt den gebildeten Niederschlag ab, wäscht ihn mit WasserIs suspended 2.5 g of 2,3-dimethoxy-10-aminoberbin in 3.75 cc of pyridine, added to 2.5 cc acetic anhydride and keeping the temperature below 30 0 C using a water bath. A crystalline mass forms, which is mixed with water at room temperature until completely dissolved and neutralized by adding triethylamine. The precipitate formed is filtered off with suction and washed with water
und kristallisiert ihn aus Aceton um. Man erhält 2,5 g 2,3-Dimethoxy-lO-acetyl-amino-berbin; F. = 196°C. Das Produkt ist unlöslich in Wasser und Äther, sehr wenig löslich in Benzol, wenig löslich in Alkohol und löslich in Aceton und Chloroform.and recrystallize it from acetone. 2.5 g of 2,3-dimethoxy-10-acetylamino-berbin are obtained; M.p. = 196 ° C. The product is insoluble in water and ether, very little soluble in benzene, little soluble in alcohol and soluble in acetone and chloroform.
Analyse: C21H24O3N2 = 325,43.Analysis: C 21 H 24 O 3 N 2 = 325.43.
Berechnet ... C 71,57, H 6,86, N 7,95%;
gefunden .... C 71,4, H 7,0, N 8,0%.Calculated ... C 71.57, H 6.86, N 7.95%;
found .... C 71.4, H 7.0, N 8.0%.
Die Verbindung ist in der Literatur noch nicht beschrieben.The connection has not yet been described in the literature.
2,3-Dimethoxy-lO-acetylamino-berbin, rechtsdrehend, F. = 164 bis 166°C, [a]l° = +294° (c = 0,85% Äthanol),2,3-Dimethoxy-10-acetylamino-berbin, clockwise, F. = 164 to 166 ° C, [a] l ° = + 294 ° (c = 0.85% ethanol),
2,3 - Dimethoxy -10 - acetylamino - berbin, linksdrehend, F. = 164 bis 166° C, [α] f = -302° (c = 1% Äthanol).2,3 - Dimethoxy -10 - acetylamino - berbin, levorotatory, m.p. 164 to 166 ° C, [α] f = -302 ° (c = 1% ethanol).
Claims (1)
Family
ID=
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