DE2003148A1 - Coronary active 1,4-dihydropyridines - Google Patents

Coronary active 1,4-dihydropyridines

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DE2003148A1
DE2003148A1 DE19702003148 DE2003148A DE2003148A1 DE 2003148 A1 DE2003148 A1 DE 2003148A1 DE 19702003148 DE19702003148 DE 19702003148 DE 2003148 A DE2003148 A DE 2003148A DE 2003148 A1 DE2003148 A1 DE 2003148A1
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radical
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alkyl
carbon atoms
atoms
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Friedrich Dr Bossert
Wulf Dr Vater
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Bayer AG
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Bayer AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/20—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 ring system
    • C07D219/06—Oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

of formula (I): are coronary dilators, antifibrillators and muscle relaxants, (where R=H, 1-6C (opt. OH-substd.) alkyl or cycloalkyl, 1-3C Oalk, benzyl, or PhC2H4 (the aromatic ring is opt. substd. by alkoxy, alkyl or halogen). R' and R'' are opt. branched 1-'C alkyl, or R' + R'' form a ring, or R''=C1-6 alkoxy (incl. cyclic), the chain being opt. interrupted by O or substd. by OH. R''' = aryl opt. substd. by NO2 and/or halogen, OH, acyloxy, alkoxy, -OCH2O-, NH2, CF3, COOH, SO3H and/or CN; benzyl; pyridyl, furyl, thienyl or pyrolyl opt. substd. by (m)ethyl or pyrimidinyl opt. subst. by (m)ethoxy; R'''' = H or 1-3C alkyl; n = 2-4).

Description

Neue 1,4-Dihydropyridinderivate Gegenstand der Erfindung sind 1,4-Dihydropyridine der allgemeinen Formel in der R Wasserstoff, einen gesättigten oder ungesättigten, geradlinigen, verzweigten oder acyclischen Alkylrest mit 1 - 6 C-Atomen, der durch eine Hydroxy- oder Alkoxygruppe 1 - 3 C-Atomen im Alkoxyrest substituiert sein kann, sowie einen Benzyl- oder Phenäthylrest, dessen Arylrest durch 1 - 3 Alkoxygruppen und/oder 1 - 2 Alkylgruppen und/oder 1 - 2 Halogenatome substituiert sein kann, wobei vorstehend erwähnte Alkyl- und Alkoxygruppen 1 - 3 C-Atome tragen können und unter Halogenatomen Fluor-, Chlor- oder Bromatome zu verstehen sind, einen geradkettigen oder verzweigten Alkylrest mit 1 - 4 C-Atomen, einen geradkettigen oder verzweigten Alkylrest mit 1 - 4 C-Atomen, wobei R' und R" auch ringförmig miteinander verbunden sein können, oder einen Alkoxyrest mit 1 - 6 C-Atomen, der geradkettig, verzweigt oder cyclisch, gesättigt oder ungesättigt sein kann und der durch 1 - 2 Sauerstoffatome in der Kette unterbrochen und durch eine Hydroxygruppe substituiert sein kann, R«' einen Arylrest, der durch 1 - 3 Nitrogruppen und/oder 1 - 3 Halogenatome und/oder 1 - 2 Hydroxygruppen und/oder 1 - 2 Acyloxygruppen und/ oder 1 - 3 Alkoxygruppen und/oder eine Dioxymethylengruppe und/oder 1 - 2 Aminogruppen und/oder 1 - 2 Acylaminogruppen und/oder eine Alkylmercaptogruppe und/oder eine Trifluormethylgruppe und/ oder eine Carboxy- und/oder Carbalkoxygruppe und/ oder einen Sulfonsäure-Rest und/oder ein Alkylsulfonylrest und/oder eine Nitrilgruppe substituiert sein kann,wobei die vorerwähnten Alkyl-, Alkoxy-, Alkylmercapto- oder Alkylsulfonylgruppen 1 - 4 C-Atome umfassen und die vorerwähnten Acylreste 1 - 2 C-Atome umfassen und unter Halogenatomen Fluor-, Chlor- oder Bromatome zu verstehen sind, einen Benzyl- oder Styrylrest, oder einen Pyridyl-, Pyrimidinyl-, Furyl-, Thienyl- oder Pyrolylrest, wobei die vorerwähnten Pyridyl-, Pyrolyl-, Thienyl- oder Furylreste durch einen Alkylrest mit 1 - 2 C-Atomen und der vorerwähnte Pyrimidinylrest zusätzlich durch 1 - 2 Methoxy-oder Äthoxygruppen substituiert sein kann, Wasserstoff oder einen niederen Alkylrest von 1 - 3 Kohlenstoffatomen und n =2-4 bedeuten.New 1,4-dihydropyridine derivatives The invention relates to 1,4-dihydropyridines of the general formula in which R is hydrogen, a saturated or unsaturated, straight, branched or acyclic alkyl radical with 1 - 6 carbon atoms, which can be substituted by a hydroxyl or alkoxy group of 1 - 3 carbon atoms in the alkoxy radical, and a benzyl or phenethyl radical, whose aryl radical can be substituted by 1-3 alkoxy groups and / or 1-2 alkyl groups and / or 1-2 halogen atoms, the aforementioned alkyl and alkoxy groups having 1-3 carbon atoms and, among halogen atoms, fluorine, chlorine or bromine atoms are to be understood as a straight-chain or branched alkyl radical with 1-4 carbon atoms, a straight-chain or branched alkyl radical with 1-4 carbon atoms, where R 'and R "can also be connected to one another in a ring, or an alkoxy radical with 1-6 C atoms, which can be straight-chain, branched or cyclic, saturated or unsaturated and which can be interrupted by 1 - 2 oxygen atoms in the chain and substituted by a hydroxyl group it has 1 - 3 nitro groups and / or 1 - 3 halogen atoms and / or 1 - 2 hydroxy groups and / or 1 - 2 acyloxy groups and / or 1 - 3 alkoxy groups and / or a dioxymethylene group and / or 1 - 2 amino groups and / or 1 - 2 acylamino groups and / or an alkyl mercapto group and / or a trifluoromethyl group and / or a carboxy and / or carbalkoxy group and / or a sulfonic acid radical and / or an alkylsulfonyl radical and / or a nitrile group can be substituted, the aforementioned alkyl, Alkoxy, alkyl mercapto or alkylsulfonyl groups comprise 1 - 4 carbon atoms and the aforementioned acyl radicals comprise 1 - 2 carbon atoms and halogen atoms are fluorine, chlorine or bromine atoms, a benzyl or styryl radical, or a pyridyl, Pyrimidinyl, furyl, thienyl or pyrolyl radical, the aforementioned pyridyl, pyrolyl, thienyl or furyl radicals being represented by an alkyl radical having 1-2 carbon atoms and the aforementioned pyrimidinyl radical additionally having from 1 to 2 methoxy or ethoxy groups can be substituted, hydrogen or a lower alkyl radical of 1-3 carbon atoms and n = 2-4.

Die EIerstellung der neuen Verbinjungen erfolgt in an sich bekannter Weise dadurch, daß man Aldehyde der allgemeinen Formel - CHO worin R"' die obengenannte Bedeutung besitzt, mit cyclischen S-Diketonen der allgemeinen Formel worin R"" und n die obengenannte Bedeutung haben, S-Dicarbonylverbindungen der allgemeinen Formel R'-CO-CH2-CO-R" worin R' und R" die obengenannte Bedeutun& besitzen und Ammoniak oder Aminen der allgemeinen Formel H2N-R worin R die obengenannte Bedeutung hat oder deren Salze in organischen Lösungsmitteln wie Alkoholen, Eisessig, Dioxan, Dimethylformamid, Dimethylsulfoxyd, halogenierten Kohlenwasserstoffen oder Pyridin bei erhöhter Temperatur, vorwiegend bei Siedetemperatur des Lösungsmitteis, oder Lösungsmittelgemisches in äquimolekularen Mengen zur Reaktion bringt.The preparation of the new compounds takes place in a manner known per se by aldehydes of the general formula --CHO in which R "'has the abovementioned meaning, with cyclic S-diketones of the general formula where R "" and n have the abovementioned meaning, S-dicarbonyl compounds of the general formula R'-CO-CH2-CO-R "in which R 'and R" have the abovementioned meaning and ammonia or amines of the general formula H2N-R in which R has the abovementioned meaning or brings its salts to reaction in organic solvents such as alcohols, glacial acetic acid, dioxane, dimethylformamide, dimethyl sulfoxide, halogenated hydrocarbons or pyridine at an elevated temperature, predominantly at the boiling point of the solvent, or solvent mixture in equimolecular amounts.

Anstelle von Ammoniak oder Aminen und B-Dicarbonylverbindungen können auch die aus beiden Komponenten resultierenden Enamine der allgemeinen Formel worin R, R' und R" die obengenannte Bedeutung besitzen, angewandt werden.Instead of ammonia or amines and B-dicarbonyl compounds, the enamines of the general formula resulting from both components can also be used wherein R, R 'and R "have the meaning given above, are used.

Bicyclische 1,4-Dihydropyridine werden dadurch erhalten, daß man Aldehyde der allgemeinen Formel R"' - OHO worin R"' die obengenannte Bedeutung besitzt, mit cyclischen B-Diketonen der allgemeinen Formel worin R" n und n die obengenannte Bedeutung besitzen und Ammoniak oder Aminen der allgemeinen Formel H2N - R oder deren Salze, worin R die obengenannte Bedeutung besitzt unter den obengenannten Bedingungen im Verhältnis 1:2:1 umsetzt.Bicyclic 1,4-dihydropyridines are obtained by aldehydes of the general formula R "'- OHO wherein R"' has the meaning given above, with cyclic B-diketones of the general formula in which R "n and n have the abovementioned meaning and ammonia or amines of the general formula H2N - R or salts thereof, in which R has the abovementioned meaning under the abovementioned conditions in a ratio of 1: 2: 1.

Eine weitere Herstellmethode von Verbindungen, bei denen R nicht Wasserstoff bedeutet besteht darin, daß man nach Helv.Another method of making compounds where R is not hydrogen means is that after Helv.

chim. Acta 41 (1958) 2066, 1,4-Dihydropyridine, bei denen R Wasserstoff bedeutet, mit Oxydationsmitteln oxydiert, die erhaltenen Pyridin-Derivate mit Alkylestern quaternisiert und diese mit geeigneten Reduktionsmitteln zu 1,4-Dihydropyridinen rUckreduziert.chim. Acta 41 (1958) 2066, 1,4-dihydropyridines in which R is hydrogen means, oxidized with oxidizing agents, the pyridine derivatives obtained with alkyl esters quaternized and this with suitable reducing agents to 1,4-dihydropyridines back-reduced.

Als Umsetzungskomponenten können z.B. Verwendung finden: Aldebyde: Benzaldehyd, 2-, 3- oder 4-Hydroxybenzaldehyd, 2,4- oder 2,6-Dihydroxybenzaldehyd, 2-, 3- oder 4-Methoxybenzaldehyd, 2-Isopropoxybenzyldehyd, 3-Butoxybenzaldehyd, 3,4,5-Trimethoxybenz-,aldehyd, 2-, 3- oder 4-Chlor/Brom/Fluorbenzaldehyd, 2,4- oder 2,6-Dichlorbenzaldehyd, 2-Methylbenzylaldehyd, 2, 4-Dimethyl benzaldehyd, 3,5-Diisopropyl-4-Hydroxybenzaldehyd, 2-, 3- oder 4-Nitrobenzaldehyd, 2,4- oder 2,6-Dinitrobenzaldehyd, 2-Nitro-6-brombenzaldehyd, 2-Nitro-3-methoxy-6-chlorbenzaldehyd, 2-Nitro-3-hydroxy-4-chlorbenzaldehyd, 3-Nitro-4-hydroxybenzaldehyd, 2-Nitro-5-hydroxybenzaldehyd, 2-Nitro-4-chlorbenzaldehyd, 2-Nitro-4-methoxybenzaldehyd, 2-Nitro-5-methoxybenzaldehyd, 2-, 3- oder 4-Trifluormethylhenzaldehyd, 2-, 3- oder 4-Cyanbenzaldehyd, 2-Nitro-4-cyanbenzaldehyd, 3-Chlor-4-cyanbenzaldehyd, Benzal-dehyd-2-(3- oder 4-)-sulfonsäure, 5-Nitrobenzaldehyd-2-sulfonsäure, Benzaldehyd-2-(3- oder 4-)carbonsäure, Benzaldehyd-2-carbonsäureäthylester, Benzaldehyd-3-carbonsäureisopropylester, Benzaldehyd-4-carbonsäurebutylester, 2-Nitrobenzaldehyd-4-carbonsäure, 3-Nitrobenzaldehyd-4-carbonsäureäthylester,, Zimtaldehyd, Hydrozimtaldehyd, 2-, 3- oder 4-Methylmercaptobenzaldehyd, 2-Methylmercapto-5-nitrobenzaldehyd, 2-Butylmercaptobenzaldehyd, 2-, 3- oder 4-Methylsulfinylbenzaldehyd, 2-, 3- oder 4-Methylsulfonylbenzaldehyd, Zimtaldehyd, Dihydrozimtaldehyd, Formylcyclohexan, 1 -Formylcyclohexen-3,1-Formyl-cyclohexin-1, 3,1-Formylcyclopenten-3, α,ß-oder -Pyridinaldehyd, 6-Methylpyridin-2-aldehyd, Pyrimidin-5-aldehyd, 4,6-Dimethoxy-pyrimidin-5-aldehyd, Furan-2-aldehyd, Thiophen-2-aldehyd und Pyrrol-2-aldehyd Acylfetteäureeater: Formylsessigsäureäthylester, Formylessigsäurebutylester, Acetessigsäuremethylester, Acetessigsäureäthylester, Acetessigsäurepropylester, Acetessigsäureisopropylester, Acetessigsäure-(α- oder ß-)bydroxyäthylester, Acetessigsäure-(d -oder ß-)methoxyäthylester, Acetessigsäure-(c(- oder ß-)äthoxyäthylester, Acetessigsäure-(& - oder ß-)propoxyäthylester, Acetessigsäurefurfurylester, Acetessigsäuretetrahydrofurfurylester, Acetessigsäureallylester, Acetessigsäuregropargylester, Acetessigsäurecyclohexylester, Propionylessigsäureäthylester, Butyrylessigsäureäthylester, Isobutyrylessigsäureäthylester Dione: Cyclopentandion-1,3, Cyclohexandion-1,3, 5-I)imethylcyclohexandion-1,3, 5-Diäthylcyclohexandion-1,3, Cyclopentandion-1,3 Amine: Methylamin, Äthylamin, Propylamin, Isopropylamin, Butylamin, Allylamin, Propargylamin, 1-Hydroxyäthylamin-2, 1,3-Dihydroxyisopropylamin, Cyclohexylamin, Benzylamin, 4-Chlorbenzylamin, 3,4-Dimethoxybenzylamin, Phenäthylamin Die neuen Verbindungen sind als Arzneimittel anwendbare Substanzen. Sie haben ein breites und vielseitiges pharmakologisches Wirkungsspektrum.The following can be used as implementation components, for example: Aldebyde: Benzaldehyde, 2-, 3- or 4-hydroxybenzaldehyde, 2,4- or 2,6-dihydroxybenzaldehyde, 2-, 3- or 4-methoxybenzaldehyde, 2-isopropoxybenzyldehyde, 3-butoxybenzaldehyde, 3,4,5-trimethoxybenz-, aldehyde, 2-, 3- or 4-chloro / bromine / fluorobenzaldehyde, 2,4- or 2,6-dichlorobenzaldehyde, 2-methylbenzylaldehyde, 2,4-dimethylbenzaldehyde, 3,5-diisopropyl-4-hydroxybenzaldehyde, 2-, 3- or 4-nitrobenzaldehyde, 2,4- or 2,6-dinitrobenzaldehyde, 2-nitro-6-bromobenzaldehyde, 2-nitro-3-methoxy-6-chlorobenzaldehyde, 2-nitro-3-hydroxy-4-chlorobenzaldehyde, 3-nitro-4-hydroxybenzaldehyde, 2-nitro-5-hydroxybenzaldehyde, 2-nitro-4-chlorobenzaldehyde, 2-nitro-4-methoxybenzaldehyde, 2-nitro-5-methoxybenzaldehyde, 2-, 3- or 4-trifluoromethylhenzaldehyde, 2-, 3- or 4-cyanobenzaldehyde, 2-nitro-4-cyanobenzaldehyde, 3-chloro-4-cyanobenzaldehyde, benzaldehyde-2- (3- or 4 -) - sulfonic acid, 5-nitrobenzaldehyde-2-sulfonic acid, benzaldehyde-2- (3- or 4-) carboxylic acid, Ethyl benzaldehyde-2-carboxylate, isopropyl benzaldehyde-3-carboxylate, butyl benzaldehyde-4-carboxylate, 2-nitrobenzaldehyde-4-carboxylic acid, 3-nitrobenzaldehyde-4-carboxylic acid ethyl ester, cinnamaldehyde, Hydrocinnamaldehyde, 2-, 3- or 4-methylmercaptobenzaldehyde, 2-methylmercapto-5-nitrobenzaldehyde, 2-butyl mercaptobenzaldehyde, 2-, 3- or 4-methylsulfinylbenzaldehyde, 2-, 3- or 4-methylsulfonylbenzaldehyde, cinnamaldehyde, dihydrocinnamaldehyde, formylcyclohexane, 1-formylcyclohexene-3,1-formyl-cyclohexyne-1, 3,1-formylcyclopentene-3, α, ß- or -Pyridine aldehyde, 6-methylpyridine-2-aldehyde, pyrimidine-5-aldehyde, 4,6-dimethoxypyrimidine-5-aldehyde, Furan-2-aldehyde, thiophene-2-aldehyde and pyrrole-2-aldehyde acyl fatty acid ester: formyl acetic acid ethyl ester, Butyl formyl acetate, methyl acetoacetate, ethyl acetoacetate, Propyl acetoacetate, isopropyl acetoacetate, acetoacetic acid (α- or ß-) hydroxyethyl ester, acetoacetic acid (d -or ß-) methoxyethyl ester, Acetoacetic acid (c (- or ß-) ethoxyethyl ester, acetoacetic acid (& - or ß-) propoxyethyl ester, Furfuryl acetoacetate, tetrahydrofurfuryl acetoacetate, allyl acetoacetate, Gropargyl acetoacetate, cyclohexyl acetoacetate, ethyl propionylacetate, Ethyl butyrylacetate, ethyl isobutyrylacetate diones: 1,3-cyclopentanedione, Cyclohexanedione-1,3, 5-I) imethylcyclohexanedione-1,3, 5-diethylcyclohexanedione-1,3, Cyclopentanedione-1,3 amines: methylamine, ethylamine, propylamine, isopropylamine, butylamine, Allylamine, propargylamine, 1-hydroxyethylamine-2, 1,3-dihydroxyisopropylamine, cyclohexylamine, Benzylamine, 4-chlorobenzylamine, 3,4-dimethoxybenzylamine, phenethylamine The new ones Compounds are substances that can be used as drugs. You have a broad one and a wide range of pharmacological effects.

Im einzelnen konnten im Tierexperiment folgende Hauptwirkungen nachgewiesen werden: 1) Die Verbindungen bewirken bei parenteraler, oraler und perlingualer Zufuhr eine deutliche und langanhaltende Erweiterung der Coronargefäße. Diese Wirkung auf die Coronargefäße wird durch einen gleichzeitigen Nitrit-ähnlichen, herzentlastenden Effekt verstärkt.In detail, the following main effects could be demonstrated in animal experiments become: 1) The compounds effect with parenteral, oral and perlingual delivery a clear and long-lasting expansion of the coronary vessels. This effect on the coronary vessels are relieved by a simultaneous nitrite-like, heart-relieving Reinforced effect.

Sie beeinflussen bzw. verändern den Herzstoffwechsel im Sinne einer Energieersparnis. They influence or change the heart metabolism in the sense of a Energy saving.

2) Die Erregbarkeit des Reizbildungs- und Erregungsleitungssystems innerhalb des Herzens wird herabgesetzt, so daß eine in therapeutischen Dosen nachweisbare Antiflimmerwirkung resultiert.2) The excitability of the stimulation and conduction system inside the heart is lowered so that one is detectable in therapeutic doses Anti-flicker effect results.

3) Der Tonus der glatten Muskulatur der Gefäße wird unter der Wirkung der Verbindungen stark vermindert. Diese gefäßspasmolytische Wirkung kann im-gesamten Gefäßsystem stattfinden oder sich mehr oder weniger isoliert in umschriebenen Gefäßgebieten (wie z.B. dem Zentralnervensystem) manifestieren.3) The tone of the smooth muscles of the vessels is under the effect of connections greatly reduced. This vasospasmolytic effect can occur throughout Vascular system take place or more or less isolated in circumscribed vascular areas (such as the central nervous system) manifest.

4) Die Verbindungen senken den Blutdruck von normotonen und hypertonen Tieren und können somit als hypertensive Mittel verwendet- werden.4) The compounds lower blood pressure from normotensive and hypertensive Animals and can thus be used as hypertensive agents.

5) Die Verbindungen haben starke muskulär-spasmolytische Wirkungen, die an der glatten Muskulatur des Kagen-Darmtraktes, des Urogenitaltraktes und des Respirationssystems deutlich werden.5) The compounds have strong muscular-spasmolytic effects, those on the smooth muscles of the Kagen intestinal tract, the urogenital tract and the The respiratory system become clear.

Beispiel 1 2-Methyl-4-(3'-pyridyl)-1,4-5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester.Example 1 2-Methyl-4- (3'-pyridyl) -1,4-5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

Eine Lösung von 107 g Pyridin-3-aldehyd, 113 g Cyclohexandion-1,3- und 130 g ß-Aminocrotonsäureäthylester in 900 ccm Alkohol und 300 cem Eisessig wird 2 Stunden zum Sieden erhitzt und anschließend in verdünnte Natronlauge gegeben. Nach dem Absaugen und Umkristallisieren aus 2 Liter Methanol werden 180 g hellgelber Kristalle vom Fp. 2360 erhalten.A solution of 107 g of pyridine-3-aldehyde, 113 g of cyclohexanedione-1,3- and 130 g of ß-aminocrotonic acid ethyl ester in 900 cc of alcohol and 300 cem of glacial acetic acid Heated to the boil for 2 hours and then poured into dilute sodium hydroxide solution. After filtration with suction and recrystallization from 2 liters of methanol, 180 g are light yellow Crystals of m.p. 2360 were obtained.

Analog wurden erhalten: a) 2-Methyl-4-(2'-pyridyl)-1,4-5,6,7,8-hexahydro-5-oxochinolin -3-carbonsäureäthylester vom Fp. 2280.The following were obtained analogously: a) 2-Methyl-4- (2'-pyridyl) -1,4-5,6,7,8-hexahydro-5-oxoquinoline 3-carboxylic acid ethyl ester, melting point 2280.

b) 2-Methyl-4-(4'-pyridyl)-1,4-5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester vom Fp. 2560.b) 2-Methyl-4- (4'-pyridyl) -1,4-5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester from m.p. 2560.

Beispiel 2 2-Methyl-4-(2'-nitrophenyl)-1,4-5,6,7,8-hexahydro-5-oxochinolin-3 -carbonsäureäthylester.Example 2 2-Methyl-4- (2'-nitrophenyl) -1,4-5,6,7,8-hexahydro-5-oxoquinoline-3 - ethyl carboxylate.

Man erhitzt die Lösung von 30 g 2-Nitrobenzaldehyd, 26 g ß-Aminocrotonsäureäthylester und 22,6 g Cyclohexandion-1,3 in 160 com Alkohol und 60 com Eisessig 2 Stunden zum Sieden, filtriert ab und erhält nach dem Kühlen und Absaugen gelbe Kristalle (36 g) die aus Alkohol umkristallisiert bei 196 -1980 schmelzen.The solution of 30 g of 2-nitrobenzaldehyde and 26 g of ß-aminocrotonic acid ethyl ester is heated and 22.6 g of 1,3-cyclohexanedione in 160 com alcohol and 60 com glacial acetic acid for 2 hours Boil, filtered off and after cooling and suctioning off yellow crystals (36 g) which, recrystallized from alcohol, melt at 196-1980.

Auf gleiche Weise wurden dargestellt: a) 2-Methyl-4-(2'-nitrophenyl)-1,4, 5,6,7,8-hexahydro-5-oxochinolincarbonsäuremethylester vom Fp. 2500 b) 2-Methyl-4-(2'-nitrophenyl)-1,4, 5,6'7,8-hexahydro-5-oxochinolin-3-carbonsäureisopropylester vom Fp. 2300 c) 2-Methyl-4-(3'-nitrophenyl)-1,4, 5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester vom Fp. 208 - 210° d) 2-Methyl-4-(4'-nitrophenyl)-1,4, 5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäuremethylester vom Fp. 208° 3) 2-Methyl-4-(4'-nitrophenyl)-1,4, 5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester vom Fp. 212° f) 2-Methyl-4-(4'-nitrophenyl)-1,4, 5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureisopropylester vom Fp.> 2500 g) 2-Methyl-4-(7'-nitro-6-chlorphnyl)-1,4, 5,6,7,8-hexahydro-5-oxo-chinolin-3-carbonsäureäthylester vom Fp.The following were prepared in the same way: a) 2-Methyl-4- (2'-nitrophenyl) -1,4, 5,6,7,8-hexahydro-5-oxoquinolinecarboxylic acid methyl ester of melting point 2500 b) 2-methyl-4- (2'-nitrophenyl) -1,4, 5,6'7,8-hexahydro-5-oxoquinoline-3-carboxylic acid isopropyl ester of melting point 2300 c) 2-methyl-4- (3'-nitrophenyl) -1,4, 5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 208-210 ° d) 2-methyl-4- (4'-nitrophenyl) -1,4, 5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid methyl ester of melting point 208 ° 3) 2-methyl-4- (4'-nitrophenyl) -1,4, 5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 212 ° f) 2-methyl-4- (4'-nitrophenyl) -1,4, 5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid isopropyl ester with a melting point of> 2500 g) Ethyl 2-methyl-4- (7'-nitro-6-chlorophenyl) -1,4, 5,6,7,8-hexahydro-5-oxo-quinoline-3-carboxylate from fp.

1760 h) 2-Methyl-4-(2'-methoxyphenyl)-1,4-5,6,7,8-hexa-4-oxochinolin-3-carbonsäureäthylester vom Fp. 251 - 2530 i) 2-Methyl-4-(4'-methoxyphenyl)-1,4-5,6,7,8-hexahydro-5-oxochinoin-3-carbonsäureäthylester vom Fp. 207 - 209° 2-htethyl-4-(4'-dimethylaminophenyl)-1*4-5,6,7,8-hexa-5-oxochinolin-3-carbonsäureäthylester vom Fp. 243° k) 2-Methyl-4-(3'-aminophenyl)-1,4, 5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester vom Fp. 223° Beispiel 3 2-Methyl-4-(4',6'-dimethoxy-5'-pyrimidyl-1,4-5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester. 1760 h) 2-Methyl-4- (2'-methoxyphenyl) -1,4-5,6,7,8-hexa-4-oxoquinoline-3-carboxylic acid ethyl ester of mp 251-2530 i) 2-Methyl-4- (4'-methoxyphenyl) -1,4-5,6,7,8-hexahydro-5-oxoquinin-3-carboxylic acid ethyl ester of m.p. 207-209 ° 2-ethyl-4- (4'-dimethylaminophenyl) -1 * 4-5,6,7,8-hexa-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 243 ° k) ethyl 2-methyl-4- (3'-aminophenyl) -1,4, 5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylate of melting point 223 ° Example 3 2-Methyl-4- (4 ', 6'-dimethoxy-5'-pyrimidyl-1,4-5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

Nach 8-stUndigem Kochen von 17 g 4,6-Dimethoxypyrimidin-5-aldehyd, 13 g ß-AminoGrotonsäureäthylester und 11,3 g Cyclohexandion-1,3 in 80 ccm Alkohol und 30 ccm Eisessig wird abgekühlt und abgesaugt. 18 g gelbe Kristalle vom Fp. 261 - 2630 (Alkohol).After boiling 17 g of 4,6-dimethoxypyrimidine-5-aldehyde for 8 hours, 13 g of ß-AminoGrotonsäureäthylester and 11.3 g of 1,3-cyclohexanedione in 80 ccm of alcohol and 30 cc of glacial acetic acid is cooled and suctioned off. 18 g of yellow crystals with a melting point of 261 - 2630 (alcohol).

Es wurde ferner dargestellt: a) 2-Methyl-4-(4'-pyrimidyl)-1,4-526,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester vom Fp. 256 - 258° Beispiel 4 2-Methyl-3-aceto-4(4'-pyridyl)-1,4 5,6,7,8-hexahydro-5-oxochinolin 21,4 g Pyridin-4-aldehyd, 22,6 g Cyclohexandion-1'3 und 20 g 2-Aminopenten-2-on-4 werden 6 Stunden in 180 ccm Alkohol und 60 ccm Eisessig zum Sieden erhitzt. Anschließend engt man im Vakuum um die Hälfte ein und fällt mit verdünnter Natronlauge.It was also shown: a) 2-Methyl-4- (4'-pyrimidyl) -1,4-526,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 256-258 °. Example 4 2-Methyl-3-aceto-4 (4'-pyridyl) -1,4 5,6,7,8-hexahydro-5-oxoquinoline 21.4 g pyridin-4-aldehyde, 22.6 g cyclohexanedione-1'3 and 20 g 2-aminopenten-2-one-4 are heated to boiling in 180 cc alcohol and 60 cc glacial acetic acid for 6 hours. Afterward you narrow in Vacuum by half and falls with dilute sodium hydroxide solution.

Nach dem Stehen über Nacht wird abgesaugt und aus Methanol umkristallisiert. 20 g gelbe Kristalle vom Fp. 2570.After standing overnight, it is filtered off with suction and recrystallized from methanol. 20 g of yellow crystals with a melting point of 2570.

Beispiel 5 1,2-Dimethyl-4-(4'-pyridyl)-1,4-5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester.Example 5 1,2-Dimethyl-4- (4'-pyridyl) -1,4-5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

Man erhitzt 58 g B-Methylaminocrotonsäureäthylester, 45,2 g Cyclohexandion-1,3 und 40 ccm Pyridin-4-aldehyd in 360 ccm Alkohol und 120 ccm Eisessig mehrere Stunden zum Sieden, engt im Vakuum um die Hälfte ein, nimmt in Wasser auf und erhält nach Zugabe von verdünnter Natronlauge 44 g hellgelbe Kristalle vom Fp. 1760 (Alkohol).58 g of ethyl B-methylaminocrotonate and 45.2 g of 1,3-cyclohexanedione are heated and 40 cc of pyridine-4-aldehyde in 360 cc of alcohol and 120 cc of glacial acetic acid for several hours to boiling, concentrated in a vacuum by half, absorbed in water and maintained Addition of dilute sodium hydroxide solution, 44 g of pale yellow crystals, melting point 1760 (alcohol).

Auf gleiche Weise wurden erhalten: a) 1,2-Dimethyl-4-(2' -pyridyl)1,4-5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester vom Fp. 142 - 144o b) 1,2-Dimethyl-4-(4'-dimethylaminophenyl)-1,4-5,6,7,8-hexhydro-5-oxochinolin-3-carbonsäureäthylester vom Fp. 154 Beispiel 6 2-Methyl-4-phenyl-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester.The following were obtained in the same way: a) 1,2-Dimethyl-4- (2'-pyridyl) 1,4-5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 142-144o b) 1,2-Dimethyl-4- (4'-dimethylaminophenyl) -1,4-5,6,7,8-hexhydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 154 Example 6 2-Methyl-4-phenyl-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester.

Nach 3-stündigem Erhitzen einer Lösung von 22 ccm Benzaldehyd, 24 g Cyclohexamdion-1,3, 26 ccm Acetessigsäureäthylester und 22 ccm Ammoniak in 200 ccm Alkohol (oder 160 ccm Alkohol und 60 ccm Eisessig) zum Sieden wird gekühlt, abgesaugt und mit Alkohol bzw. Äther gewaschen.After heating a solution of 22 cc benzaldehyde, 24 g of 1,3-cyclohexamdione, 26 cc of ethyl acetoacetate and 22 cc of ammonia in 200 cc alcohol (or 160 cc alcohol and 60 cc glacial acetic acid) for boiling is cooled, sucked off and washed with alcohol or ether.

Weiße Kristalle vom Fp. 2630 (Alkohol) 47 g.White crystals, m.p. 2630 (alcohol) 47 g.

Auf gleiche Weise wurden dargestellt: a) 2-Methyl-4-(2'-chlorphenyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester, Fp. 218° b) 2-Methyl-4-(4'-chlorphenyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester, Fp. 2380 c) 2-Methyl-4-(2',4'-dichlorphenyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester, Fp. 2450 d) 2-Methyl-4-(2',6'-dichlorphenyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester, Fp. > 260° e) 2-Methyl-4-(α-thienyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester, Fp. 236° f) 2-Methyl-4-(4'-carbmethoxyphenyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester, Fp. 2000 -g) 2-Methyl-4-(4'-hydroxyphenyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester, Fp. 252° h) 2-Methyl-4-(3'-hydroxy-4'-nitrophenyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureäthylester, Fp. 2150 i) 2-Methyl-4-(3'-nitro-6'-chlorphenyl)-1,4,5,6,7,8-hexa-0 hydro-5-oxochinolin-3-carbonsäurepropargylester, Fp. 220° j) 2-Methyl-4-(3'-nitro-4'-chlorphenyl)-1,4,5,6,7,8-hexahydro-5-oxochinolin-3-carbonsäureisopropylester, Fp.>280° k) 2-Methyl-4-(3'-nitro-4'-chlorphenyl)-1,4,5,6,7,8-hexahydro-3-oxochinolin-3-carbonsäurefurfurylester, Fp. 190° Beispiel 7 1,2,3,4,5,6,7,8,9,10-Dekahydro-9-(4'nitrophenyl)-1,3-dioxoacridin.The following were prepared in the same way: a) 2-Methyl-4- (2'-chlorophenyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester, Mp. 218 ° b) 2-methyl-4- (4'-chlorophenyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester, Mp. 2380 c) 2-methyl-4- (2 ', 4'-dichlorophenyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester, Mp. 2450 d) 2-methyl-4- (2 ', 6'-dichlorophenyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester, Mp.> 260 ° e) 2-methyl-4- (α-thienyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester, Mp. 236 ° f) 2-methyl-4- (4'-carbmethoxyphenyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester, M.p. 2000 g) 2-methyl-4- (4'-hydroxyphenyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester, Mp. 252 ° h) 2-methyl-4- (3'-hydroxy-4'-nitrophenyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester, Mp. 2150 i) 2-methyl-4- (3'-nitro-6'-chlorophenyl) -1,4,5,6,7,8-hexa-0 hydro-5-oxoquinoline-3-carboxylic acid propargyl ester, Mp. 220 ° j) 2-methyl-4- (3'-nitro-4'-chlorophenyl) -1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid isopropyl ester, Mp.> 280 ° k) 2-methyl-4- (3'-nitro-4'-chlorophenyl) -1,4,5,6,7,8-hexahydro-3-oxoquinoline-3-carboxylic acid furfuryl ester, Mp. 190 ° Example 7 1,2,3,4,5,6,7,8,9,10-decahydro-9- (4'nitrophenyl) -1,3-dioxoacridine.

151 g 4-Nitrobenzaldehyd, 250 g Cyclohexandion-1,3 und 100 ccm Ammoniak werden in 500 com methanol 6 Stunden zum Sieden erhitst. Es wird heiß abgesaugt und der Rückstand mit Methanol nachgewaschen.151 g of 4-nitrobenzaldehyde, 250 g of 1,3-cyclohexanedione and 100 cc of ammonia are heated to boiling in 500 com methanol for 6 hours. It is sucked off hot and the residue was washed with methanol.

Dunkelbraune Kristalle (150 g) Fp.>310° Auf gleiche Weise wurden dargestellt: a) 1,2,3,4,5,6,7,8,9,10-Dekahydro-9-(3'-nitrophenyl)-1,8-dioxoacridin, Fp.>260° b) 1,2,3,4,5,6,7,8,9,10-Dekahydro-9-(4'-aminophenyl)-1,8-dioioacridin, Pp. 2470 c) 1,2,3,4,5,6,7,8,9,10-Dekahydro-9-(3'-aminophenyl)-1,8-dioxoacridin, Fp. >260° d) 1,2,3,4,5,6,7,8,9,10-Dekahydro-9-(4'-dimethylaminophenyl)-1,8-dioxoacridin, Fp.>260° e) 1,2,3,4,5,6,7,8,9,10-Dekahydro-9-α-pyridyl-1,8-dioxoacridin, Fp.>260° f) 1,2,3,4,5,6,7,8,9,10-Dekahydro-9-ß-pyridyl-1,8-dioxoacridin, Fp.>260 g) 1,2,3,4,5,6,7,8,9,10-Dekahydro-9-γ-pyridyl-1,8-dioxoacridin, Fp.>260° h) 1,2,3,4,5,6,7,8,9,10-Dekahydro-3,6-Tetramthyl-9-(2'-nitrophenyl)-1,8-dioxoacridin, Fp. 258 - 2600 i) 1,2,3,4,5,6,7,8,9,10-Dekahydro-3,6-tetramethyl-9-(4'-nitrophenyl)-1,8-dioxoacridin, Fp. 300° Beispiel 8 N-Methyl-1,2,3,4,5,6,7,8,9,10-Dekahydro-9-α-pyridyl-1,8-d ioxoacridin., Man läßt die Lösung von 20 com Pyridin-2-aldehyd, 42 g Cyclohexandion-1,3 und 18 ccm Methylaminlösung in 250 ml Alkohol 2 Stunden bei Zimmertemperatur rühren, erhitzt anschießend mehrere Stunden zum Sieden und- erhält nach dem Abkühlen und Absaugen gelbe Kristalle vom Fp. 236 - 2380 (12 g, Chloroform/ Ligroin).Dark brown crystals (150 g), melting point> 310 ° shown: a) 1,2,3,4,5,6,7,8,9,10-decahydro-9- (3'-nitrophenyl) -1,8-dioxoacridine, Mp> 260 ° b) 1,2,3,4,5,6,7,8,9,10-decahydro-9- (4'-aminophenyl) -1,8-dioacridine, Pp. 2470 c) 1,2,3,4,5,6,7,8,9,10-decahydro-9- (3'-aminophenyl) -1,8-dioxoacridine, Mp> 260 ° d) 1,2,3,4,5,6,7,8,9,10-decahydro-9- (4'-dimethylaminophenyl) -1,8-dioxoacridine, Mp> 260 ° e) 1,2,3,4,5,6,7,8,9,10-decahydro-9-α-pyridyl-1,8-dioxoacridine, Mp> 260 ° f) 1,2,3,4,5,6,7,8,9,10-decahydro-9-ß-pyridyl-1,8-dioxoacridine, mp> 260 g) 1,2,3,4,5,6,7,8,9,10-decahydro-9-γ-pyridyl-1,8-dioxoacridine, m.p.> 260 ° h) 1,2,3,4,5,6,7,8,9,10-decahydro-3,6-tetramthyl-9- (2'-nitrophenyl) -1,8-dioxoacridine, M.p. 258-2600 i) 1,2,3,4,5,6,7,8,9,10-decahydro-3,6-tetramethyl-9- (4'-nitrophenyl) -1,8-dioxoacridine, M.p. 300 ° Example 8 N-methyl-1,2,3,4,5,6,7,8,9,10-decahydro-9-α-pyridyl-1,8-d ioxoacridin., The solution of 20 com pyridine-2-aldehyde, 42 g cyclohexanedione-1,3 and stir 18 cc methylamine solution in 250 ml alcohol for 2 hours at room temperature, then heated to the boil for several hours and-obtained after cooling and Yellow crystals of melting point 236-2380 (12 g, chloroform / ligroin) are filtered off with suction.

Auf gleiche Weise wurden dargestellt: N-Methyl-1,2,3,4,5,6,7,8,9,10-Dekahydro-9-(4'-nitrophenyl) 1,8-dioxoacridin vom Fp. 295°The following were prepared in the same way: N-methyl-1,2,3,4,5,6,7,8,9,10-decahydro-9- (4'-nitrophenyl) 1,8-dioxoacridine, mp 295 °

Claims (7)

Patentansprüche 1. 1,4-Dihydropyridine der allgemeinen Formel in der R Wasserstoff, einen gesättigten oder ungesättigten, geradlinigen, verzweigten oder cyclischen Alkylrest mit 1 - 6 C-Atoven, der durch eine Hydroxy- oder Alkoxygruppe mit 1 - 3 C-Atomen im Alkoxyrest substituiert sein kann, sowie einen Benzyl- oder Phenäthylrest, dessen Arylrest durch 1 - 3 Alkoxygruppen und/oder 1 - 2 Alkylgruppen und/oder 1 - 2 HaIogenatome substituiert sein kann, wobei vorstehend erwähnte Alkyl- und Alkoxygruppen 1 - 3 C-Atome tragen können und unter Halogenatomen Fluor-, Chlor- oder Bromatome zu verstehen sind, einen geradkettigen oder verzweigten Alkylrest mit 1 - 4 C-Atomen, einen geradkettigen oder verzweigten Alkylrest mit 1 - 4 C-Atomen, wobei R und R" auch ringförmig miteinander verbunden sein können, oder einen Alkoxyrest mit 1 - 6 0-Atomen, der geradkettig, verzweigt oder cyclisch, gesättigt oder ungesättigt sein kann und der durch t - 2 Sauerstoffatome in der, Kette unterbrochen und durch eine Hydroxygruppe substituiert sein kann, einen Arylrest, der durch 1 - 3 Nitrogruppen und/ oder 1 - 3 Halogenatome und/oder 1 - 2 Hydroxygruppen land/oder 1 - 2 Acyloxygruppen und/oder 1 - 3 Alkoxygruppen und/oder eine Dioxymethylengruppe und/ oder 1 - 2 Aminogruppen-und/oder 1 - 2 Acylaminogruppen und/oder eine Alkylmercaptogruppe und/oder eine Trifluormethylgruppe und/oder eine Carboxy-und/oder Carbalkoxygruppe und/oder einen Sulfonsäure-Rest und/oder ein Alkylsulfonylrest und/oder eine Ritrilgruppe substituiert sein kann, wobei die rorerwähnten Alkyl-, Alkoxy-, Alkylmercapto- oder Alkylsulfonylgruppen 1 - 4 C-Atome umfassen und die vorerwähnten Acylreste 1 - 2 -Atome umfassen und unter Halogenatomen Pluor-, Chlor- oder Bromatome zu verstehen sind, einen Benzyl- oder Styrylrest, oder einen Pyridyl-, Pyrimidinyl-, Furyl-, Thienyl-oder Pyrolylrest, wobei die vorerwähnten Pyridyl-, Pyrolyl-, Thienyl- oder Purylreste durch einen Alkylrest nit 1 - 2 C-Atomen und der vorerwähnte Pyrimidinylrest zusätzlich durch 1 - 2 Methoxy- oder Äthoxygruppen substituiert sein kann, R"" Wasserstoff oder einen niederen Alkylrest von 1 - 3 Kohlenstoffatomen und n = 2 - 4 bedeuten.Claims 1. 1,4-dihydropyridines of the general formula in which R is hydrogen, a saturated or unsaturated, straight, branched or cyclic alkyl radical with 1 - 6 carbon atoms, which can be substituted by a hydroxyl or alkoxy group with 1 - 3 carbon atoms in the alkoxy radical, and a benzyl or phenethyl radical , the aryl radical of which can be substituted by 1-3 alkoxy groups and / or 1-2 alkyl groups and / or 1-2 halogen atoms, whereby the aforementioned alkyl and alkoxy groups can carry 1-3 carbon atoms and, among halogen atoms, fluorine, chlorine or Bromine atoms are to be understood as meaning a straight-chain or branched alkyl radical with 1-4 carbon atoms, a straight-chain or branched alkyl radical with 1-4 carbon atoms, where R and R ″ can also be connected to one another in a ring, or an alkoxy radical with 1-6 0 atoms, which can be straight-chain, branched or cyclic, saturated or unsaturated and which can be interrupted by t - 2 oxygen atoms in the chain and substituted by a hydroxyl group, an aryl radical, de r by 1-3 nitro groups and / or 1-3 halogen atoms and / or 1-2 hydroxy groups and / or 1-2 acyloxy groups and / or 1-3 alkoxy groups and / or a dioxymethylene group and / or 1-2 amino groups and / or 1 - 2 acylamino groups and / or an alkyl mercapto group and / or a trifluoromethyl group and / or a carboxy and / or carbalkoxy group and / or a sulfonic acid radical and / or an alkylsulfonyl radical and / or a ritrile group can be substituted, where the above-mentioned alkyl , Alkoxy, alkyl mercapto or alkylsulfonyl groups comprise 1 - 4 carbon atoms and the aforementioned acyl radicals comprise 1 - 2 atoms and halogen atoms are to be understood as fluorine, chlorine or bromine atoms, a benzyl or styryl radical, or a pyridyl, Pyrimidinyl, furyl, thienyl or pyrolyl radical, the aforementioned pyridyl, pyrolyl, thienyl or puryl radicals being replaced by an alkyl radical having 1-2 carbon atoms and the aforementioned pyrimidinyl radical being additionally replaced by 1-2 methoxy or ethoxy groups, see below may be substituted, R "" is hydrogen or a lower alkyl radical of 1-3 carbon atoms and n = 2-4. 2. Arzneimittel, gekennzeichnet durch einen Gehalt an einer Verbindung gesäß Anspruch 1.2. Medicinal product, characterized by a content of a compound according to claim 1. 3. Verfahren zur Herstellung von Arzneimitteln, dadurch gekennzeichnet, daß man Verbindungen gemäß Anspruch 1 als Wirkstoff verwendet.3. Process for the production of pharmaceuticals, characterized in that that one uses compounds according to claim 1 as an active ingredient. 4. Mittel mit Coroharwirkung, gekennzeichnet durch einen Gehalt an einer Verbindung gemäß Anspruch 1.4. Agent with Corohar effect, characterized by a content of a compound according to claim 1. 5. Verfahren zur Herstellung von Mitteln mit Coronarwirkung, dadurch gekennzeichnet, daß man Verbindungen gemäß Anspruch 1 als Wirkstoff verwendet.5. Process for the preparation of agents with coronary effects, thereby characterized in that compounds according to claim 1 are used as active ingredients. 6. Oral applizierbare Mittel mit Ooronarwirkung gekennzeichnet durch einen Gehalt an einer Verbindung gemäß Anspruch 1.6. Orally applicable agents with oral effect characterized by a content of a compound according to claim 1. 7. Verfahren zur Herstellung oral applizierbarer Mittel mit Coronarwirkung, dadurch gekennzeichnet, daß man Verbindungen gemäß Anspruch 1 als Wirkstoff verwendet.7. Process for the production of orally administrable agents with coronary effects, characterized in that compounds according to Claim 1 are used as active ingredients.
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* Cited by examiner, † Cited by third party
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US4546186A (en) * 1983-12-14 1985-10-08 American Home Products Corporation 1,4,5,6,7,8-Hexahydro-2-methyl-5-oxo-4-(2-thiazolyl)-3-quinoline carboxylic acid 2-methyl(phenylmethyl)amino ethyl ester and pharmaceutically acceptable salts
US4853392A (en) * 1987-07-17 1989-08-01 Pfizer Inc. Fused 1,4-dihydropyridines as antiallergy and antiinflammatory agents
EP0342182A1 (en) * 1988-05-13 1989-11-15 Gerot-Pharmazeutika Gesellschaft m.b.H. Derivatives of 5-aminomethyl-2-furan methanol, their preparation and use
EP0539153A1 (en) * 1991-10-21 1993-04-28 Zeneca Limited Acridine derivative as therapeutic agent
EP0539154A1 (en) * 1991-10-21 1993-04-28 Zeneca Limited Acridine-1,8-dione-derivatives as therapeutic agents
WO1994008966A1 (en) * 1992-10-20 1994-04-28 Zeneca Limited Quinolone and acridinone derivatives for the treatment of urinary incontinence
US5455253A (en) * 1992-10-20 1995-10-03 Zeneca Limited Heterocyclic derivatives
WO1995028388A1 (en) * 1994-04-14 1995-10-26 Zeneca Limited Quinolone derivative for treatment of urinary incontinence
EP0705830A1 (en) 1994-08-25 1996-04-10 Bayer Ag 2,3-Cyclic condensed 1,4-dihydropyridines, process for their preparation and their use as K-channel modulators
EP0823426A1 (en) * 1996-08-07 1998-02-11 F. Hoffmann-La Roche Ag Xanthene and acridine derivatives and their use
WO2000051986A1 (en) * 1999-03-04 2000-09-08 Abbott Laboratories Cyclopentanone dihydropyridine compounds useful as potassium channel openers
WO2002010103A1 (en) * 2000-08-02 2002-02-07 Astrazeneca Ab PROCESS FOR SYNTHESIS OF α,β-UNSATURATED KETONES
WO2002010134A1 (en) * 2000-08-02 2002-02-07 Astrazeneca Ab Process for asymmetric synthesis of substituted 1,4-dihydropyridines
WO2007095424A1 (en) * 2006-02-10 2007-08-23 Janssen Pharmaceutica N.V. Novel tricyclic dihydropyrazines as potassium channel openers
WO2013178821A1 (en) * 2012-06-01 2013-12-05 Leibniz-Institut für Altersforschung - Fritz-Lipmann-Institut e.V. (FLI) Inhibitors of the notch signalling pathway and secretion for use in medicine

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4546186A (en) * 1983-12-14 1985-10-08 American Home Products Corporation 1,4,5,6,7,8-Hexahydro-2-methyl-5-oxo-4-(2-thiazolyl)-3-quinoline carboxylic acid 2-methyl(phenylmethyl)amino ethyl ester and pharmaceutically acceptable salts
US4853392A (en) * 1987-07-17 1989-08-01 Pfizer Inc. Fused 1,4-dihydropyridines as antiallergy and antiinflammatory agents
EP0342182A1 (en) * 1988-05-13 1989-11-15 Gerot-Pharmazeutika Gesellschaft m.b.H. Derivatives of 5-aminomethyl-2-furan methanol, their preparation and use
AT391471B (en) * 1988-05-13 1990-10-10 Gerot Pharmazeutika NEW DERIVATIVES OF 5-AMINOMETHYL-2-FURANMETHANOL, THEIR PRODUCTION AND USE
US5017586A (en) * 1988-05-13 1991-05-21 Gerot-Pharmazeutika Gesellschaft M.B.H. 5-dialkylaminomethyl-2-furanomethanol derivatives having anti-hypertensive properties
US5484792A (en) * 1991-10-21 1996-01-16 Imperial Chemical Industries, Plc 1,8-(2H,5H)-acridinedione therapeutic agents
EP0539153A1 (en) * 1991-10-21 1993-04-28 Zeneca Limited Acridine derivative as therapeutic agent
EP0539154A1 (en) * 1991-10-21 1993-04-28 Zeneca Limited Acridine-1,8-dione-derivatives as therapeutic agents
US5258390A (en) * 1991-10-21 1993-11-02 Imperial Chemical Industries Plc 9-(3 cyanophenyl) hexahydro-1,8 acridinedione
US5340819A (en) * 1991-10-21 1994-08-23 Imperial Chemical Industries Plc Method for treating urinary incontinence using 9-(3-nitrophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H) acridinedione
US5622964A (en) * 1992-10-20 1997-04-22 Zeneca Limited Heterocyclic derivatives
US5455253A (en) * 1992-10-20 1995-10-03 Zeneca Limited Heterocyclic derivatives
WO1994008966A1 (en) * 1992-10-20 1994-04-28 Zeneca Limited Quinolone and acridinone derivatives for the treatment of urinary incontinence
WO1995028388A1 (en) * 1994-04-14 1995-10-26 Zeneca Limited Quinolone derivative for treatment of urinary incontinence
US6121284A (en) * 1994-08-25 2000-09-19 Bayer Aktiengesellschaft 2,3-bridged 1,4-dihydropyridines, and their use as medicaments
EP0705830A1 (en) 1994-08-25 1996-04-10 Bayer Ag 2,3-Cyclic condensed 1,4-dihydropyridines, process for their preparation and their use as K-channel modulators
US6162918A (en) * 1996-08-07 2000-12-19 Hoffmann-La Roche Inc. Xanthene and acridine derivatives
CN1100759C (en) * 1996-08-07 2003-02-05 弗·哈夫曼-拉罗切有限公司 Xanthene and arcridine derivative and its use
US5969139A (en) * 1996-08-07 1999-10-19 Hoffmann-La Roche Inc. Acridine derivatives
EP0823426A1 (en) * 1996-08-07 1998-02-11 F. Hoffmann-La Roche Ag Xanthene and acridine derivatives and their use
WO2000051986A1 (en) * 1999-03-04 2000-09-08 Abbott Laboratories Cyclopentanone dihydropyridine compounds useful as potassium channel openers
US6518279B2 (en) 1999-03-04 2003-02-11 Abbott Laboratories Cyclopentanone dihydropyridine compounds useful as potassium channel openers
WO2002010103A1 (en) * 2000-08-02 2002-02-07 Astrazeneca Ab PROCESS FOR SYNTHESIS OF α,β-UNSATURATED KETONES
WO2002010134A1 (en) * 2000-08-02 2002-02-07 Astrazeneca Ab Process for asymmetric synthesis of substituted 1,4-dihydropyridines
US6995289B2 (en) 2000-08-02 2006-02-07 Astrazeneca Ab Process for synthesis of alpha, beta-unsaturated ketones
US7074931B2 (en) 2000-08-02 2006-07-11 Astrazeneca Ab Process for asymmetric synthesis of substituted 1,4 -dihydropyridines
WO2007095424A1 (en) * 2006-02-10 2007-08-23 Janssen Pharmaceutica N.V. Novel tricyclic dihydropyrazines as potassium channel openers
US7674793B2 (en) 2006-02-10 2010-03-09 Janssen Pharmaceutica Nv Tricyclic dihydropyrazines as potassium channel openers
WO2013178821A1 (en) * 2012-06-01 2013-12-05 Leibniz-Institut für Altersforschung - Fritz-Lipmann-Institut e.V. (FLI) Inhibitors of the notch signalling pathway and secretion for use in medicine
US9828344B2 (en) 2012-06-01 2017-11-28 LEIBNIZ-INSTITUT FÜR ALTERSFORSCHUNG FRITZ-LIPMANN-INSTITUT e.V. (FLI) Inhibitors of the notch signaling pathway and secretion for use in medicine

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