DE1445505B2 - 2-PHENYLAMINO-1,3-DIAZACYCLOPENTENE- (2) SUBSTITUTED IN THE PHENYL CORE - Google Patents
2-PHENYLAMINO-1,3-DIAZACYCLOPENTENE- (2) SUBSTITUTED IN THE PHENYL COREInfo
- Publication number
- DE1445505B2 DE1445505B2 DE1963B0073766 DEB0073766A DE1445505B2 DE 1445505 B2 DE1445505 B2 DE 1445505B2 DE 1963B0073766 DE1963B0073766 DE 1963B0073766 DE B0073766 A DEB0073766 A DE B0073766A DE 1445505 B2 DE1445505 B2 DE 1445505B2
- Authority
- DE
- Germany
- Prior art keywords
- dichloro
- methylphenyl
- diazacyclopentene
- amino
- acid
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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 ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Z —NH-CZ -NH-C
(D(D
N-H N-H
-CH,-CH,
worin Z einen 2,6-Dichlor-4-methylphenyl oder 2,4-Dichlor-6-methylphenylrest bedeutet, sowie deren Säureadditionssalze.wherein Z is a 2,6-dichloro-4-methylphenyl or 2,4-dichloro-6-methylphenyl radical, as well as their acid addition salts.
2. Verfahren zur Herstellung der substituierten Phenylamino - 1,3 - diazäcyclopentene - (2) nach Anspruch 1, dadurch gekennzeichnet, daß man in an sich bekannter Weise entweder2. Process for the preparation of the substituted phenylamino - 1,3 - diazäcyclopentene - (2) according to Claim 1, characterized in that either in a known manner
a) ein Isothiuroniumsalz der allgemeinen Formel IIa) an isothiuronium salt of the general formula II
Z —NH-CZ -NH-C
NHNH
SR'SR '
HXHX
(Π)(Π)
worin Z die angegebene Bedeutung besitzt, R' einen niederen Alkylrest und X einen Säurerest
bedeutet, gegebenenfalls unter Verwendung eines geeigneten Lösungsmittels mit Äthylendiamin umsetzt
oder daß man
b) eine Verbindung der allgemeinen Formel IIIin which Z has the meaning given, R 'is a lower alkyl radical and X is an acid radical, optionally reacting with ethylenediamine using a suitable solvent, or reacting with ethylenediamine
b) a compound of the general formula III
3535
H2C-H2C- H 2 CH 2 C-
-NH2 -NH 2
-N —C —NH-Z-N-C-NH-Z
H Il
Y H Il
Y
(III)(III)
4040
worin Z die angegebene Bedeutung besitzt und Y ein Schwefel- oder Sauerstoffatom bedeutet, der Pyrolyse unterwirft und daß man gegebenenfalls die so erhaltenen Verbindungen in üblicher Weise in ihre Säureadditionssalze überführt.wherein Z has the meaning given and Y is a sulfur or oxygen atom, subjected to pyrolysis and that, if appropriate, the compounds thus obtained in a customary manner Way converted into their acid addition salts.
3. Pharmazeutische Zubereitungen, bestehend aus einer oder mehreren Verbindungen nach Anspruch 1 und üblichen Hilfs- und/oder Trägerstoffen. 3. Pharmaceutical preparations consisting of one or more compounds according to claim 1 and usual auxiliaries and / or carriers.
2,4-Dichlor-6-methylphenylrest bedeutet, sowie deren Salze wertvolle pharmazeutische Eigenschaften aufweisen. 2,4-dichloro-6-methylphenyl radical means, and the salts thereof have valuable pharmaceutical properties.
Nach der Erfindung können die neuen Verbindungen auf verschiedenen Wegen in an sich bekannter Weise hergestellt werden.According to the invention, the new compounds can be in various ways known per se Way to be made.
a) So kann man ein Isothiuroniumsalz der allgemeinen Formel IIa) So you can use an isothiuronium salt of the general formula II
Es wurde gefunden, daß substituierte Phenylaminol,3-diazacyclopentene-(2) der allgemeinen Formel IIt has been found that substituted phenylaminol, 3-diazacyclopentene- (2) of the general formula I.
Z —NH-CZ -NH-C
N-CH,N-CH,
N-CH2
HN-CH 2
H
60 Z —NH-C 60 Z -NH-C
NHNH
SR'SR '
HXHX
(I)(I)
worin Z einen 2,6-Dichlor-4-methylphenyl- oder worin Z die vorstehend angegebene Bedeutung besitzt, R' einen niederen Alkylrest und X einen Säurerest bedeutet, mit Äthylendiamin umsetzen.in which Z is a 2,6-dichloro-4-methylphenyl or in which Z has the meaning given above, R 'is a lower alkyl radical and X is an acid radical, react with ethylenediamine.
Die Umsetzung wird vorzugsweise ohne Verwendung eines Lösungsmittels durch einfaches Erhitzen der Reaktionskomponenten auf etwa 100 bis 200° C durchgeführt. Diese Methode führt in kurzer Zeit zu befriedigenden Ausbeuten an dem gewünschten Endprodukt. Prinzipiell kann die Reaktion auch bei niedrigeren Temperaturen (60 bis 14O0C) unter Zusatz eines geeigneten Lösungsmittels, das vorzugsweise polare Gruppen enthält, wie Wasser oder niedere Alkohole, ablaufen; es wurde jedoch festgestellt, daß hierbei lange Reaktionszeiten in Kauf genommen werden müssen, wenn man gute Ausbeute erzielen will. Bei Verwendung 2,6-disubstituierter Phenylderivate führt selbst langes Erhitzen in dem betreffenden Lösungsmittel lediglich zu einer geringfügigen Ausbeute an Reaktionsprodukt. Auch eine Variante des zuletzt angegebenen Verfahrens, der Ablauf der Reaktion unter Druck, eventuell unter Verwendung eines internen Gases, bringt keine Steigerung der Ausbeute.The reaction is preferably carried out by simply heating the reaction components to about 100 to 200.degree. C. without using a solvent. This method leads to satisfactory yields of the desired end product in a short time. In principle, the reaction can (60 to 14O 0 C) with the addition of a suitable solvent which preferably contains polar groups, such as water or lower alcohols, to proceed at lower temperatures; however, it has been found that long reaction times have to be accepted if a good yield is to be achieved. When using 2,6-disubstituted phenyl derivatives, even prolonged heating in the solvent in question only leads to a slight yield of the reaction product. Even a variant of the process mentioned last, the course of the reaction under pressure, possibly using an internal gas, does not bring about an increase in the yield.
Das als Ausgangsmaterial benötigte Isothiuroniumsalz der Formel II erhält man beispielsweise durch Erhitzen eines in bekannter Weise aus einem entsprechend substituierten Anilin und Ammoniumrhodanid hergestellten Thioharnstoffe (s. Houben — Weyl, Methoden der organischen Chemie, Band 9, Seite 887) mit einer Alkylverbindung, wie einem Alkylhalogenid oder Dialkylsulfat in einem geeigneten Lösungsmittel, z. B-. einem niederen Alkohol." The isothiuronium salt of the formula II required as starting material is obtained, for example, from Heating in a known manner from an appropriately substituted aniline and ammonium thiocyanate produced thioureas (see Houben - Weyl, Methods of Organic Chemistry, Volume 9, page 887) with an alkyl compound, such as an alkyl halide or dialkyl sulfate in a suitable solvent, e.g. B-. a lower alcohol. "
b) Eine weitere Methode zur Herstellung der neuen 2-Phenylamino-l,3-diazacyclopentene-(2) besteht im Ringschluß eines entsprechend substituierten N-Phenyl - N' - (β - aminoäthyl) - (thio) - harnstoffs der allgemeinen Formel IIIb) Another method for the preparation of the new 2-phenylamino-l, 3-diazacyclopentene- (2) consists in the ring closure of an appropriately substituted N-phenyl-N '- (β- aminoethyl) - (thio) - urea of the general formula III
55 H7C-NH, 55 H 7 C-NH,
H2C-N-C-NH-ZH 2 CNC-NH-Z
(III)(III)
worin Z die angegebene Bedeutung besitzt und Y ein Schwefel- oder Sauerstoffatom bedeutet, durch Pyrolyse.wherein Z has the meaning given and Y is a sulfur or oxygen atom, through Pyrolysis.
Die benötigten Ausgangsverbindungen können durch Reaktion eines substituierten Phenyliso(thio)-cyanats mit Äthylendiamin nach den Angaben in Journal Organic Chemistry, Band 24, S. 818 (1959) erhalten werden.The required starting compounds can be obtained by reacting a substituted phenyl iso (thio) cyanate with ethylenediamine according to the information in Journal Organic Chemistry, Volume 24, p. 818 (1959) can be obtained.
Die Verbindungen der allgemeinen Formel I können nach üblichen Methoden in die entsprechenden physiologisch unbedenklichen Säureadditionssake überführt werden, z. B. durch Behandlung mit einer organischen oder anorganischen Säure, wie Mineralsäuren, z. B. Chlorwasserstoflsäure oder Bromwasserstoffsäure, Salpetersäure, Essigsäure, Oxalsäure, Weinsäure, Fumarsäure, Maleinsäure, Zitronensäure, Ascorbinsäure oder Propionsäure.The compounds of general formula I can be converted into the corresponding physiologically acceptable acid addition sake by customary methods, e.g. B. by treatment with an organic or inorganic acid such as mineral acids, e.g. B. hydrochloric acid or hydrobromic acid, nitric acid, acetic acid, oxalic acid, tartaric acid, fumaric acid, maleic acid, citric acid, ascorbic acid or propionic acid.
Die Herstellung von Säureadditionssalzen ist insbesondere dann vorteilhaft, wenn wasserlösliche, für Injektionszwecke geeignete Verbindungen hergestellt werden sollen.The preparation of acid addition salts is particularly advantageous when water-soluble, for Connections suitable for injections should be made.
Die erfindungsgemäßen Verbindungen wurden gegen verschiedene bekannte Substanzen gleicher Wirkungsrichtung hinsichtlich der blutdrucksenkenden Wirkung geprüft. Als Versuchstiere dienten Kaninchen in Urethannarkose; die Zufuhr der Substanzen erfolgte intravenös.The compounds according to the invention became the same against various known substances Direction of action tested with regard to the antihypertensive effect. Served as experimental animals Rabbits under urethane anesthesia; the substances were administered intravenously.
Die folgende Tabelle gibt einen Überblick über blutdrucksenkende Wirkung, Toxizität und therapeutischen Index der neuen Verbindungen sowie dreier bekannter Vergleichssubstanzen.The following table gives an overview of antihypertensive effects, toxicity and therapeutic Index of the new compounds and three known comparison substances.
Mit den erfindungsgemäßen Verbindungen wird ein fester und lang anhaltender Schlaf hervorgerufen, aus dem aber die Versuchsperson jederzeit erweckt werden kann. Die neuen Substanzen bieten somit einen wesentlichen Vorteil vor den üblichen Schlafmitteln, vor allem den Barbiturate^ bei denen eine überdosierung, die ζ. B. eine Schlafdauer von 20 bis 30 Stunden erzeugt, stets in den ersten Stunden zu einer fast narkoseähnlichen Bewußtlosigkeit führt aus der die Patienten nur durch starke Reize kurzfristig erweckt werden können und dann stark benommen sind.With the compounds according to the invention a solid and long-lasting sleep is brought about, but from which the test subject can be awakened at any time. The new substances thus offer an essential advantage over the usual sleeping pills, especially the barbiturates ^ in which one overdose, the ζ. B. a sleep duration of 20 to 30 hours generated, always leading to an anesthetic-like unconsciousness in the first few hours from which the patient can only be briefly awakened by strong stimuli and then become very dazed are.
Die erfindungsgemäßen Verbindungen sollen in der Medizin als Hypotensiva bzw. Sedativa Verwendung
finden. Sie lassen sich zu allen für pharmazeutische Zwecke üblichen Zubereitungsformen verarbeitea
Zum Beispiel kann man daraus Pillen, Dragees, Tabletten, Suppositorien, Emulsionen, Lösungen
und Injektionslösungen herstellen.
Die folgenden Beispiele sollen die Erfindung näherThe compounds according to the invention are intended to be used in medicine as hypotensives or sedatives. They can be processed into all preparation forms customary for pharmaceutical purposes. For example, they can be used to produce pills, coated tablets, tablets, suppositories, emulsions, solutions and injection solutions.
The following examples are intended to further illustrate the invention
2020th
erläutern.explain.
2525th
2-(2,4-Dichlor-6-methylphenyl)-aminol,3-diazacycIopenten-(2)-oxalat 2- (2,4-dichloro-6-methylphenyl) aminol, 3-diazacyciopentene (2) oxalate
2-(2,6-Dichlor-2- (2,6-dichloro-
4-methyl-4-methyl-
phenyl)-amino-phenyl) -amino-
1,3-diazacyclo-1,3-diazacyclo-
penten-(2)pentene (2)
2-(2,4-Dichlor-6-m'ethyl- 2- (2,4-dichloro-6-m'ethyl-
phenyl)-amino-1,3-diazacyclo- phenyl) -amino-1,3-diazacyclo-
p'enten-(2)p'enten- (2)
3030th
0,030.03
0,250.25
63,8 212763.8 2127
/Vi/Ai Cl Uli L LCl./ Vi / Ai Cl Uli L LCl.
1 ■?1 ■?
S 72mS 72m
2-(0-Piperidino-2- (0-piperidino-
/3-phenyl-äthyl-/ 3-phenyl-ethyl-
amino)-imid-amino) -imide-
azolin-(2)azoline- (2)
(DT-AS(DT-AS
11 35917)11 35917)
2-(/S-Piperidino-2 - (/ S-piperidino-
äthylamino)-ethylamino) -
imidazolin-(2)-imidazoline- (2) -
4,34.3
0,20.2
245245
47n47n
175175
0,89 110.89 11
11651165
12,5 g 2,4 - Dichlor - 6 - methyl - anilin (hergestellt durch Chlorieren von o-Toluidin in Eisessig und Ferrichlorid nach Adams: Journ. Am. Soc, Band 72, Seite 2454), 170 ml Wasser, 37 ml konzentrierte Salzsäure und 36,8 g Ammoniumrhodanid werden 7 Stunden unter Rückfluß erhitzt. Die Ausbeute an ThiohamstofrVerbindung beträgt, aus Äther umkristallisiert, 18 g vom Fp. 183 bis 184° C.12.5 g of 2,4 - dichloro - 6 - methyl - aniline (manufactured by chlorinating o-toluidine in glacial acetic acid and ferric chloride according to Adams: Journ. At the. Soc, Volume 72, page 2454), 170 ml water, 37 ml concentrated Hydrochloric acid and 36.8 g of ammonium thiocyanate are refluxed for 7 hours. The yield of thiourea compound is, recrystallized from ether, 18 g of melting point 183 to 184 ° C.
18 g ThioharnstoffVerbindung werden mit 33 g18 g of thiourea compound are added to 33 g
Methyljodid in 300 ml Methanol etwa 3 Stunden unter Rückfluß erhitzt. Danach wird das Lösungsmittel im Vakuum abgezogen, der Rückstand mit 7 g Äthylendiamin versetzt und die Mischung unter Rühren etwa 1 Stunde auf 1800C erhitzt. Hierbei entweicht Mercaptan. Das so erhaltene Reaktionsgemisch wird in 2n-Salzsäure aufgenommen, die Lösung mit Chloroform ausgeschüttelt, über Kohle filtriert und unter Zugabe von Ammoniak schwach alkalisch eingestellt. Die Base wird sodann mitMethyl iodide in 300 ml of methanol is heated under reflux for about 3 hours. Thereafter, the solvent is removed in vacuo, the residue treated with 7 g of ethylenediamine, and the mixture heated with stirring for about 1 hour at 180 0 C. Mercaptan escapes in the process. The reaction mixture obtained in this way is taken up in 2N hydrochloric acid, the solution is shaken out with chloroform, filtered over charcoal and adjusted to be weakly alkaline with the addition of ammonia. The base is then with
Chloroform extrahiert, die Lösung getrocknet, über Kohle filtriert und das Lösungsmittel im Vakuum abdestilliert.Chloroform extracted, the solution dried over Filtered charcoal and the solvent was distilled off in vacuo.
Das Oxalat des 2-{2,4-Dichlor-6-methylphenyl)- The oxalate of 2- {2,4-dichloro-6-methylphenyl) -
amino-l^-diaza-cyclopenten-^) erhält man nach Zu-amino-l ^ -diaza-cyclopentene- ^) is obtained after adding
50 fügen einer alkoholischen Oxalsäurelösung durch50 paste an alcoholic oxalic acid solution through
Ausäthern. Nach Umkristallisation aus Isopropanol/ Äther beträgt die Ausbeute 9,5 g vom Fp. 261 bis 263° C.Ether. After recrystallization from isopropanol / ether b etr the yield 9.5 g, mp 261 AEGT. To 263 ° C.
Analog Beispiel 1 kann 2-(2,6-Dichlor-4-methyl-Analogously to Example 1, 2- (2,6-dichloro-4-methyl-
phenyl) - amino - 1,3 - diazaeyclopenten - (2) vom pp. 156° C erhalten werden.phenyl) - amino - 1,3 - diazaeyclopentene - (2) from pp. 156 ° C can be obtained.
980980
AnnAnn
106106
1131687)1131687)
Darüber hinaus besitzen die neuen Substanzen eine gute sedative Wirkung, die bei den obengenannten blutdrucksenkenden Dosen bereits nachweisbar ist, jedoch erst in höherer Dosierung deutlich zutage tritt.In addition, the new substances have a good sedative effect, as in the case of the above antihypertensive doses are already detectable, but only clearly revealed in higher doses occurs.
2-(2,6-Dichlor-4-methylphenyl)-amino-l,3-diazacyclopenten-(2) .... 0,1 mg2- (2,6-dichloro-4-methylphenyl) -amino-1,3-diazacyclopentene- (2) .... 0.1 mg
^1 ? »s^e ] 3o'o mg^ 1 ? »S ^ e] 3o'o mg
τ ^f^u stärke 40 mgτ ^ f ^ u strength 40 mg
Ma'gSsiumstearat '.WY.'.'.V.'.'.'.'.V. l|o mgMa'gSsium stearate '.WY.'. '. V.'. '.'. '. V. l | o mg
90,0 mg90.0 mg
TablettenTablets
2-(2,6-Dichlor-4-methyl-phenyl)-2- (2,6-dichloro-4-methyl-phenyl) -
amino-l,3-diazacyclopenten-{2) 0,4 mgamino-1,3-diazacyclopentene- {2) 0.4 mg
Milchzucker 54,6 mgLactose 54.6 mg
Maisstärke 30,0 mgCorn starch 30.0 mg
Lösliche Stärke 4,0 mgSoluble starch 4.0 mg
Magnesiumstearat 1,0 mgMagnesium stearate 1.0 mg
90,0 mg90.0 mg
Beispiel B
TablettenExample B.
Tablets
2-(2,6-Dichlor-4-methylphenyl)-2- (2,6-dichloro-4-methylphenyl) -
amino-l,3-diazacyclopenten-{2) 0,2 mgamino-1,3-diazacyclopentene- {2) 0.2 mg
Milchzucker 54,8 mgLactose 54.8 mg
Maisstärke 30,0 mgCorn starch 30.0 mg
Lösliche Stärke 4,0 mgSoluble starch 4.0 mg
Magnesiumstearat 1,0 mgMagnesium stearate 1.0 mg
90,0 mg90.0 mg
TablettenTablets
2-(2,6-Dichlor-4-methylphenyl)-2- (2,6-dichloro-4-methylphenyl) -
amino-l,3-diazacyclopenten-{2) 0,8 mgamino-1,3-diazacyclopentene- {2) 0.8 mg
Milchzucker 54,2 mgMilk sugar 54.2 mg
Maisstärke 30,0 mgCorn starch 30.0 mg
Lösliche Stärke 4,0 mgSoluble starch 4.0 mg
Magnesiumstearat 1,0 mgMagnesium stearate 1.0 mg
90,0 mg90.0 mg
Beispiel C
TablettenExample C
Tablets
2-(2,4-Dichlor-6-methylphenyl)-2- (2,4-dichloro-6-methylphenyl) -
amino-l,3-diazacyclopenten-{2) 0,2 mgamino-1,3-diazacyclopentene- {2) 0.2 mg
Milchzucker 54,8 mgLactose 54.8 mg
Maisstärke 30,0 mgCorn starch 30.0 mg
Lösliche Stärke 4,0 mgSoluble starch 4.0 mg
Magnesiumstearat 1,0 mgMagnesium stearate 1.0 mg
90,0 mg Tabletten90.0 mg tablets
2-(2,4-Dichlor-6-methylphenyl)-2- (2,4-dichloro-6-methylphenyl) -
amino-l,3-diazacyclopenten-{2) 0,8 mgamino-1,3-diazacyclopentene- {2) 0.8 mg
Milchzucker 54,2 mgMilk sugar 54.2 mg
Maisstärke . 30,0 mgCornstarch. 30.0 mg
Lösliche Stärke 4,0 mgSoluble starch 4.0 mg
Magnesiumstearat „ 1,0 mgMagnesium stearate "1.0 mg
90,0 mg90.0 mg
Beispiel D
Tropfen (0,1 mg in 1 ml = 20 Tropfen)Example D
Drops (0.1 mg in 1 ml = 20 drops)
2-(2,6-Dichlor-4-methylphenyl)-ammo-1,3-diaza- 2- (2,6-dichloro-4-methylphenyl) -ammo-1,3-diaza-
cyclopenten-(2) 0,01 gcyclopentene (2) 0.01 g
p-Benzoesäure-methylester 0,07 gmethyl p-benzoate 0.07 g
p-Benzoesäure-propylester 0,03 gp-Benzoic acid propyl ester 0.03 g
Entmineralisiertes Wasser, ad ... 100,00 mlDemineralized water, ad ... 100.00 ml
IOIO
2020th
3030th
4040
4545
5555
6o6o
Beispiel E Tropfen (0,1 mg in 1 ml = 20 Tropfen)Example E drops (0.1 mg in 1 ml = 20 drops)
2-{2,4-Dichlor-4-methylphenyl)-amino-1,3-diaza- 2- {2,4-dichloro-4-methylphenyl) -amino-1,3-diaza-
cyclopenten-(2) 0,02 gcyclopentene (2) 0.02 g
p-Benzoesäure-methylester 0,07 gmethyl p-benzoate 0.07 g
p-Benzoesäure-propylester 0,03 gp-Benzoic acid propyl ester 0.03 g
Entmineralisiertes Wasser, ad ... 100,00 mlDemineralized water, ad ... 100.00 ml
Beispiel F AmpullenExample F Ampoules
2-(2,6-Dichlor-4-methylphenyl)-amino-l,3-diaza- 2- (2,6-dichloro-4-methylphenyl) -amino-1,3-diaza-
cyclopenten-(2) 0,025 mgcyclopentene- (2) 0.025 mg
Natriumchlorid 18,0 mgSodium chloride 18.0 mg
Dest Wasser, ad 2,0 mlDest water, ad 2.0 ml
Beispiel G AmpullenExample G Ampoules
2-(2,4-Dichlor-6-methylphenyl)-amino-l,3-diaza- 2- (2,4-dichloro-6-methylphenyl) -amino-1,3-diaza-
cyclopenten-(2) 0,05 mgcyclopentene- (2) 0.05 mg
Natriumchlorid 18,0 mgSodium chloride 18.0 mg
DesL Wasser, ad 2,0 mlDesL water, ad 2.0 ml
Beispiel H AmpullenExample H ampoules
2-(2,4-Dichlor-6-methylphenyl)-amino-1,3-diaza- 2- (2,4-dichloro-6-methylphenyl) -amino-1,3-diaza-
cyclopenten-(2) 0,05 mgcyclopentene- (2) 0.05 mg
Natriumchlorid 18,0 mgSodium chloride 18.0 mg
Dest. Wasser, ad 2,0 mlDistilled water, ad 2.0 ml
Beispiel I SuppositorienExample I suppositories
2-(2,6-Dichlor-4-methylphenyl)-amino-1,3-diaza- 2- (2,6-dichloro-4-methylphenyl) -amino-1,3-diaza-
cyclopenten-(2) 0,4 mgcyclopentene (2) 0.4 mg
Milchzucker 244,6 mgMilk sugar 244.6 mg
Zäpfchenmasse, ad 1,7 gSuppository mass, ad 1.7 g
Beispiel K SuppositorienExample K suppositories
2-(2,6-Dichlor-4-methylphenyl)-amino-l,3-diaza- 2- (2,6-dichloro-4-methylphenyl) -amino-1,3-diaza-
cyclopenten-(2) 0,8 mgcyclopentene (2) 0.8 mg
Milchzucker 244,2 mgMilk sugar 244.2 mg
Zäpfchenmasse, ad 1,7 gSuppository mass, ad 1.7 g
Beispiel L SuppositorienExample L suppositories
2-(2,4-Dichlor-6-methylphenyl)-amino-1,3-diaza- 2- (2,4-dichloro-6-methylphenyl) -amino-1,3-diaza-
cyclopenten-(2) 0,8 mgcyclopentene (2) 0.8 mg
Milchzucker 244,2 mgMilk sugar 244.2 mg
Zäpfchenmasse, ad 1,7 gSuppository mass, ad 1.7 g
Claims (1)
Priority Applications (21)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL123037D NL123037C (en) | 1963-10-04 | ||
| DE1963B0073766 DE1445505B2 (en) | 1963-10-04 | 1963-10-04 | 2-PHENYLAMINO-1,3-DIAZACYCLOPENTENE- (2) SUBSTITUTED IN THE PHENYL CORE |
| US327806A US3236857A (en) | 1961-10-09 | 1963-12-03 | 2-(phenyl-amino)-1, 3-diazacyclopentene-(2) substitution products |
| DE19641445538 DE1445538A1 (en) | 1963-10-04 | 1964-07-31 | Process for the preparation of new substituted phenylamino-1,3-diazacyclopentene- (2) |
| CH1193264A CH437316A (en) | 1963-10-04 | 1964-09-14 | Process for the preparation of substituted phenylamino-1,3-diazacyclopentene (2) compounds |
| CH1193164A CH451169A (en) | 1963-10-04 | 1964-09-14 | Process for the preparation of new substituted phenylamino-1,3-diazacyclopentene- (2) |
| CH1189367A CH451172A (en) | 1963-10-04 | 1964-09-14 | Process for the preparation of new substituted phenylamino-1,3-diazacyclopentene- (2) |
| SE1110764A SE313310B (en) | 1963-10-04 | 1964-09-16 | |
| SE1071068A SE353721B (en) | 1963-10-04 | 1964-09-16 | |
| FI201764A FI44913C (en) | 1963-10-04 | 1964-09-23 | Process for the preparation of new substituted phenylamino-1,3-diazacyclopentenes- (2) having an antihypertensive and sedative effect |
| GB39420/64A GB1034938A (en) | 1963-10-04 | 1964-09-28 | 2-phenylamino-1,3-diazacyclopent-2-enes |
| FR990056A FR3968M (en) | 1963-10-04 | 1964-10-01 | |
| FR990057A FR1448765A (en) | 1963-10-04 | 1964-10-01 | Process for making novel phenylamino-1, 3-diazacyclopentenes- (2) -substituted |
| DK486964A DK108364C (en) | 1963-10-04 | 1964-10-02 | Process for the preparation of substituted phenylamino-1,3-diazacyclopentenes- (2) -, or acid addition salts thereof. |
| NL6411516A NL6411516A (en) | 1961-10-09 | 1964-10-02 | |
| BR16314264A BR6463142D0 (en) | 1963-10-04 | 1964-10-02 | PROCESS FOR OBTAINING NEW PHENYLAMINE-1,3- DIAZACICATIVE |
| BE653933D BE653933A (en) | 1963-10-04 | 1964-10-02 | |
| IL2218664A IL22186A (en) | 1963-10-04 | 1964-10-04 | Phenylamino-1,3-diazacyclopentenes,process for their preparation and compositions containing them |
| DK482765A DK117000B (en) | 1963-10-04 | 1965-09-20 | Process for the preparation of substituted phenylamino-1,3-diazacyclopentenes (2) or acid addition salts thereof. |
| US515479A US3454701A (en) | 1961-10-09 | 1965-12-21 | 2 - (phenyl - amino) - 1,3 - diazacyclopentene - (2) substitution products for reducing blood pressure |
| FI260071A FI49614C (en) | 1963-10-04 | 1971-09-17 | Process for the preparation of substituted phenylamino-1,3-diazacyclopentener- (2) by vasoconstrictive, antihypertensive and sedative action. |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1963B0073766 DE1445505B2 (en) | 1963-10-04 | 1963-10-04 | 2-PHENYLAMINO-1,3-DIAZACYCLOPENTENE- (2) SUBSTITUTED IN THE PHENYL CORE |
| DEB0077921 | 1964-07-31 | ||
| DEB0077922 | 1964-07-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE1445505A1 DE1445505A1 (en) | 1969-10-02 |
| DE1445505B2 true DE1445505B2 (en) | 1976-12-16 |
Family
ID=27209240
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1963B0073766 Granted DE1445505B2 (en) | 1961-10-09 | 1963-10-04 | 2-PHENYLAMINO-1,3-DIAZACYCLOPENTENE- (2) SUBSTITUTED IN THE PHENYL CORE |
| DE19641445538 Pending DE1445538A1 (en) | 1963-10-04 | 1964-07-31 | Process for the preparation of new substituted phenylamino-1,3-diazacyclopentene- (2) |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19641445538 Pending DE1445538A1 (en) | 1963-10-04 | 1964-07-31 | Process for the preparation of new substituted phenylamino-1,3-diazacyclopentene- (2) |
Country Status (11)
| Country | Link |
|---|---|
| BE (1) | BE653933A (en) |
| BR (1) | BR6463142D0 (en) |
| CH (3) | CH451172A (en) |
| DE (2) | DE1445505B2 (en) |
| DK (2) | DK108364C (en) |
| FI (2) | FI44913C (en) |
| FR (2) | FR1448765A (en) |
| GB (1) | GB1034938A (en) |
| IL (1) | IL22186A (en) |
| NL (1) | NL123037C (en) |
| SE (2) | SE313310B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1545628A1 (en) * | 1965-10-01 | 1970-06-25 | Boehringer Sohn Ingelheim | Process for the preparation of antihypertensive and sedative derivatives of 2- (2-haloanilino) -1,3-diazacyclopentene- (2) |
| BE754832A (en) * | 1969-08-14 | 1971-02-15 | Beecham Group Ltd | IMINAZOLINES |
| US4125620A (en) | 1974-10-01 | 1978-11-14 | Boehringer Ingelheim Gmbh | 2-[(2',6'-Disubstituted-phenyl)-imino]-imidazolidines and salts thereof |
| MTP837B (en) | 1977-11-07 | 1979-10-22 | Hoffman La Roche And Co Aktien | Derivatives 2 finino-imidazolidire |
| DE2806811A1 (en) * | 1978-02-17 | 1979-08-23 | Boehringer Sohn Ingelheim | NEW SUBSTITUTED 2-PHENYLIMINO-IMIDAZOLIDINE, THEIR ACID-ADDITIONAL SALTS, THESE MEDICINAL PRODUCTS AND METHOD FOR MANUFACTURING THE SAME |
| DE2854659A1 (en) * | 1978-12-18 | 1980-07-10 | Boehringer Sohn Ingelheim | NEW 3,4-DISUBSTITUTED 2-PHENYLIMINO IMIDAZOLIDINES, THEIR ACID ADDITION SALTS, THE MEDICINAL PRODUCTS CONTAINING THEM AND METHOD FOR THE PRODUCTION THEREOF |
| CA1175434A (en) | 1980-09-10 | 1984-10-02 | Hoffmann-La Roche Limited | ¬(2-phenylamino-1-imidazolidinyloxy)methyl| pyridine 1-oxide derivatives |
| US4444782A (en) * | 1982-12-23 | 1984-04-24 | Smithkline Beckman Corporation | 2(4-tert.-Butyl-2,6-dichlorophenyl-imino)imidazolidine and use as an anti-hypertension agent |
-
0
- NL NL123037D patent/NL123037C/xx active
-
1963
- 1963-10-04 DE DE1963B0073766 patent/DE1445505B2/en active Granted
-
1964
- 1964-07-31 DE DE19641445538 patent/DE1445538A1/en active Pending
- 1964-09-14 CH CH1189367A patent/CH451172A/en unknown
- 1964-09-14 CH CH1193164A patent/CH451169A/en unknown
- 1964-09-14 CH CH1193264A patent/CH437316A/en unknown
- 1964-09-16 SE SE1110764A patent/SE313310B/xx unknown
- 1964-09-16 SE SE1071068A patent/SE353721B/xx unknown
- 1964-09-23 FI FI201764A patent/FI44913C/en active
- 1964-09-28 GB GB39420/64A patent/GB1034938A/en not_active Expired
- 1964-10-01 FR FR990057A patent/FR1448765A/en not_active Expired
- 1964-10-01 FR FR990056A patent/FR3968M/fr not_active Expired
- 1964-10-02 DK DK486964A patent/DK108364C/en active
- 1964-10-02 BE BE653933D patent/BE653933A/xx unknown
- 1964-10-02 BR BR16314264A patent/BR6463142D0/en unknown
- 1964-10-04 IL IL2218664A patent/IL22186A/en unknown
-
1965
- 1965-09-20 DK DK482765A patent/DK117000B/en unknown
-
1971
- 1971-09-17 FI FI260071A patent/FI49614C/en active
Also Published As
| Publication number | Publication date |
|---|---|
| CH451169A (en) | 1968-05-15 |
| DK108364C (en) | 1967-11-27 |
| IL22186A (en) | 1968-06-20 |
| BR6463142D0 (en) | 1973-07-19 |
| GB1034938A (en) | 1966-07-06 |
| DE1445538A1 (en) | 1969-02-20 |
| FI44913C (en) | 1972-02-10 |
| NL123037C (en) | |
| DE1445505A1 (en) | 1969-10-02 |
| DK117000B (en) | 1970-03-09 |
| FR3968M (en) | 1966-02-28 |
| FR1448765A (en) | 1966-03-18 |
| SE313310B (en) | 1969-08-11 |
| BE653933A (en) | 1965-04-02 |
| FI49614C (en) | 1975-08-11 |
| CH437316A (en) | 1967-06-15 |
| CH451172A (en) | 1968-05-15 |
| FI44913B (en) | 1971-11-01 |
| SE353721B (en) | 1973-02-12 |
| FI49614B (en) | 1975-04-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| SH | Request for examination between 03.10.1968 and 22.04.1971 | ||
| C3 | Grant after two publication steps (3rd publication) | ||
| E77 | Valid patent as to the heymanns-index 1977 |