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DE3044072A1 - Bis-aminomethyl-anthraquinone derivs. - with antiprotozoal, antiviral and interferon inducing activity - Google Patents

Bis-aminomethyl-anthraquinone derivs. - with antiprotozoal, antiviral and interferon inducing activity

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Publication number
DE3044072A1
DE3044072A1 DE19803044072 DE3044072A DE3044072A1 DE 3044072 A1 DE3044072 A1 DE 3044072A1 DE 19803044072 DE19803044072 DE 19803044072 DE 3044072 A DE3044072 A DE 3044072A DE 3044072 A1 DE3044072 A1 DE 3044072A1
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Germany
Prior art keywords
anthraquinone
bis
formula
aminomethyl
methyl
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DE19803044072
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German (de)
Inventor
Wolfgang Dr. 6072 Dreieichenhain Raether
Heinrich Dr. 6233 Kelkheim Rolly
Erhardt Dr. 6233 Kelkheim Winkelmann
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Hoechst AG
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Hoechst AG
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Publication date
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Priority to DE19803044072 priority Critical patent/DE3044072A1/en
Priority to EP81109738A priority patent/EP0052853A1/en
Priority to ES507234A priority patent/ES507234A0/en
Priority to GR66570A priority patent/GR78224B/el
Priority to JP56185574A priority patent/JPS57118540A/en
Priority to FI813709A priority patent/FI813709L/en
Priority to IL64336A priority patent/IL64336A0/en
Priority to ZA818107A priority patent/ZA818107B/en
Priority to DK519581A priority patent/DK519581A/en
Priority to PT74023A priority patent/PT74023B/en
Priority to NO813974A priority patent/NO813974L/en
Priority to KR1019810004526A priority patent/KR830007489A/en
Priority to AR287543A priority patent/AR227341A1/en
Priority to AU77766/81A priority patent/AU7776681A/en
Publication of DE3044072A1 publication Critical patent/DE3044072A1/en
Priority to ES516225A priority patent/ES8306734A1/en
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C50/00—Quinones
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    • C07—ORGANIC CHEMISTRY
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    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07C50/00—Quinones
    • C07C50/26—Quinones containing groups having oxygen atoms singly bound to carbon atoms
    • C07C50/34—Quinones containing groups having oxygen atoms singly bound to carbon atoms the quinoid structure being part of a condensed ring system having three rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
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    • C07—ORGANIC CHEMISTRY
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    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
    • C07D295/112—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C07D295/116—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hydrogenated Pyridines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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Abstract

Bis-aminomethyl-anthraquinone derivs. of formula (I) and their salts with acids are new. R1 and R2 are each H or 1-4C alkyl, or R1 and R2 together form a 4-6C alkylene residue so that N(R1)(R2) is a 5- to 7-membered heterocyclic ring which may contain N, O or S as a further heteroatom and which may be substd. by 1-4C alkyl; and R3 is H or OH). The new cpds. can be used for combatting protozoal diseases, in humans and animals, e.g. amoebiasis due to Entamoeba histolytica. In addn., the cpds. have a direct or (due to interferon-induction) indirect activity against influenza and encephalomyocarditis viruses. On account of their interferon-inducing activity, the cpds. can be used against virus and cancer diseases. In addition, the new cpds. (esp. those in which R3 is OH) are effective against trichomoniasis.

Description

Bis-Aminomethyl-anthrachinon-Derivate, Verfahren zu ihrerBis-aminomethyl-anthraquinone derivatives, process for their

Herstellung, sie enthaltende Mittel und ihre Verwendung 2,6-Diamino-anthrachinone sind nach DE-OS 25 38 878 und Anthrachinon-bis-amidine sind nach DE-OS 25 21 357 zur Bekämpfung von Protozoenerkrankungen wie Amöbiasis bekannt.Manufacture, compositions containing them and their use 2,6-diamino-anthraquinones are according to DE-OS 25 38 878 and anthraquinone-bis-amidines are according to DE-OS 25 21 357 known for combating protozoal diseases such as amebiasis.

Gegenstand der Erfindung sind Bis-Aminomethyl-anthrachinen-Derivate der Formel I und ihre Salze mit physiologisch verträglichen Säuren, worin R¹ und R² gleich oder verschieden sind und Wasserstoff, geradkettiges oder verzweigtes Alkyl mit ein bis vier Kohlenstoffatomen, wie Methyl, Äthyl, Propyl, Isopropyl, Butyl, Isobutyl, oder R¹ und R² zusammen eine Alkylenkette mit vier, fünf oder sechs Kohlenstoffatomen dje mit dem Stickstoffatom einen fEin£-, sechs- ocler siebengliedrigen heterocyclischen Ring bilden, der ein weiteres Heteroatom aus der Gruppe Stickstoff, Sauerstoff und Schwefel enthalten kann und seinerseits durch geradkettiges oder verzweigtes alkyl mit ein bis vier Kohlenstoffatomen substituiert -sein kann, wie Pyrrolidin, 2-Methyl-pyrrolidin, 2,5-Dimethyl-pyrrolidin, Piperidin, 2-Methyl-piperidin, 2,6-Dimethyl-piperidin, 3-Methyl-piperidin, 4-Methylpiperidin, 4-Dimethylamino-piperidin, 4-Piperidino-piperidin, Morpholin, 2-Methyl-morpholin, 2,6-Dimethyl-morpholin, Piperazin, N-Methyl-piperazin, N-Äthyl-piperazin, N-Propylpiperazin, N-Butyl-piperazin, N-2-Hydroxyäthyl-piperazin, N-3-Hydroxypropyl-piperazin, N-Methyl-hexahydropyrimidin, N-Methyl-homopiperazin, Hexamethylenimin oder Thiomorpholin, bedeuten.The invention relates to bis-aminomethyl-anthraquinene derivatives of the formula I and their salts with physiologically acceptable acids, in which R¹ and R² are identical or different and are hydrogen, straight-chain or branched alkyl having one to four carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or R¹ and R² together have an alkylene chain four, five or six carbon atoms each with the nitrogen atom form a single, six or seven-membered heterocyclic ring, which can contain a further heteroatom from the group consisting of nitrogen, oxygen and sulfur and which in turn is substituted by straight-chain or branched alkyl with one to four carbon atoms -can be, such as pyrrolidine, 2-methyl-pyrrolidine, 2,5-dimethyl-pyrrolidine, piperidine, 2-methyl-piperidine, 2,6-dimethyl-piperidine, 3-methyl-piperidine, 4-methylpiperidine, 4-dimethylamino -piperidine, 4-piperidino-piperidine, morpholine, 2-methyl-morpholine, 2,6-dimethyl-morpholine, piperazine, N-methyl-piperazine, N-ethyl-piperazine, N-propylpiperazine, N-butyl-piperazine, N -2-H hydroxyethyl-piperazine, N-3-hydroxypropyl-piperazine, N-methyl-hexahydropyrimidine, N-methyl-homopiperazine, hexamethyleneimine or thiomorpholine.

Bevorzugt sind Verbindungen der Formel 1, in welcher sich die beiden Aminomethyl-Reste in 2,6- oder 2,7-Position am Anthrachinongerüst befinden.Compounds of formula 1 in which the two are preferred are preferred Aminomethyl residues are in the 2,6- or 2,7-position on the anthraquinone skeleton.

Bevorzugt sind weiter Verbindungen der Formel I, in welcher beide subst:ituierten Amino-Gruppen ein N-Alkylpiperazin darstellen.Also preferred are compounds of the formula I in which both substituted amino groups represent an N-alkylpiperazine.

Gegenstand der Erfindung ist auch ein Verfahren zur Herstellung von Bis-Aminomethyl-anthrachinon-Derivaten der Formel I sowie von deren Salzen, das dadurch gekennzeichnet ist, daß man a) ein substituiertes Dimethyl-anthrachinon der Formel II worin Y ein Halogellatom wie Chlor, Brom, Jod, eine Acyloxygruppe oder eine Arylsulfonyloxygruppe bedeutet, mit einem Amin der Formel III worin R1 und R2 die zu Formel I erwähnten Bedeutungen haben, umsetzt und gegebenenfalls durch Zugabe einer physiologisch verträglichen Säure in ein Salz überführt, oder b) ein Anthrachinon-dicarbonsäureamid der Formel IV worin R1 und R2 die zu Formel I erwähnten Bedeutungen haben, reduziert und die als Zwischenprodukt erhalteneri Anthrahydrochinon-Derivate zu Anthrachinon-Derivaten der Formel I oxydiert und gegebenenfalls durch Zugabe einer physiologisch verträglichen Säure in ein Salz überführt.The invention also relates to a process for the preparation of bis-aminomethyl-anthraquinone derivatives of the formula I and their salts, which is characterized in that a) a substituted dimethyl-anthraquinone of the formula II wherein Y is a halogen atom such as chlorine, bromine, iodine, an acyloxy group or an arylsulfonyloxy group, with an amine of the formula III in which R1 and R2 have the meanings mentioned for formula I, are converted and optionally converted into a salt by adding a physiologically acceptable acid, or b) an anthraquinone dicarboxamide of the formula IV in which R1 and R2 have the meanings mentioned for formula I, and the anthrahydroquinone derivatives obtained as an intermediate are oxidized to anthraquinone derivatives of the formula I and optionally converted into a salt by adding a physiologically acceptable acid.

Die Herstellung der Verbindungen der Formel I nach Verfahren a) wird zweckmäßig mit äquivalenten Mengen der Ausgangsstoffe der Formel II (1 Mol) und der Formel III (2 Mol) in Gegenwart eines säurebindenden Mittels (2 Mol) oder auch durch Anwendung eines Uberschusses des Amins der Formel III (4 Mol) durchgeführt. The preparation of the compounds of formula I by process a) is expediently with equivalent amounts of the starting materials of the formula II (1 mol) and of the formula III (2 mol) in the presence of an acid-binding agent (2 mol) or else carried out by using an excess of the amine of formula III (4 moles).

Als Ausgangsstoffe der Formel II kommen beispielsweise in Frage 2,6- bzw. 2,7-Bis-Chlormethyl-,-Brommethyl-, -Jodmethyl-, -Acetoxymethyl-, -Benzoyloxymethyl-, -Methansulfonyloxymethyl, -Benzolsulfonyloxymethyl-und -4-Toluolsulfonyloxymethyl-anthrachinon. As starting materials of the formula II, for example, 2,6- or 2,7-bis-chloromethyl, bromomethyl, iodomethyl, acetoxymethyl, benzoyloxymethyl, -Methanesulfonyloxymethyl, -Benzenesulfonyloxymethyl- and -4-Toluenesulfonyloxymethyl-anthraquinone.

Bevorzugt ist 2,6- bzw. 2,7-Bis-Brommethyl-anthrachinon. 2,6- or 2,7-bis-bromomethyl-anthraquinone is preferred.

Die Verbindungen können erhalten werden durch Bromierung von 2,6- bzw. 2,7-Dimethylanthrachinon z.B. mittels N-Bromsuccinimid. 2,6- bzw. 2,7-Dimethylanthrachinon können nach der deutschen Patentschrift 494 433 durch Diensynthese aus Benzochinon und Isopren dargestellt werden. The compounds can be obtained by bromination of 2,6- or 2,7-dimethylanthraquinone, for example by means of N-bromosuccinimide. 2,6- or 2,7-dimethylanthraquinone can according to German Patent 494 433 by diene synthesis from benzoquinone and isoprene can be represented.

Als Ausgangs stoffe der Formel III kommen beispielsweise in Frage Ammoniak oder Ammoniakbildner, wie Ammoniumcarbonat, Harnstoff, Urotropin, ferner Dimethylamin, Diäthylamin, Dipropylamin, Diisopropylamin, Dibutylamin, Diisobutylamin, Methyläthylamin, Methylpropylamin, Methylbutylamin, Pyrrolidin, 2-Methyl-pyrrolidin, 2,5-Dimethyl-pyrrolidin, Piperidin, 2-Methyl-piperidin, 2,6-Dimethyl-piperidin, 3-Methyl-piperidin,, 4-Methyl-piperidin, 4-Dimethylaminopiperidin, 4-Piperidino-piperidin, Morpholin, 2-Methylmorpholin, 2,6-Dimethyl-morpholin, Piperazin, N-Methylpiperidin, N-Äthyl-piperidin, N-Propyl-piperidin, N-Butylpiperazin, N-2-Hydroxyäthyl-piperidin, N-3-Hydroxypropyl- piperidin, N-Methyl-hexahydropyrimidin, N-Methyl-homopiperidin, Hexamethylenimin und Thiomorpholin.As starting materials of the formula III, for example, come into question Ammonia or ammonia formers, such as ammonium carbonate, urea, urotropine, also Dimethylamine, diethylamine, dipropylamine, diisopropylamine, dibutylamine, diisobutylamine, Methylethylamine, methylpropylamine, methylbutylamine, pyrrolidine, 2-methyl-pyrrolidine, 2,5-dimethyl-pyrrolidine, piperidine, 2-methyl-piperidine, 2,6-dimethyl-piperidine, 3-methyl-piperidine, 4-methyl-piperidine, 4-dimethylaminopiperidine, 4-piperidino-piperidine, Morpholine, 2-methylmorpholine, 2,6-dimethylmorpholine, piperazine, N-methylpiperidine, N-ethyl piperidine, N-propyl piperidine, N-butyl piperazine, N-2-hydroxyethyl piperidine, N-3-hydroxypropyl piperidine, N-methyl-hexahydropyrimidine, N-methyl-homopiperidine, Hexamethyleneimine and thiomorpholine.

Die Ausgangsstoffe der Formel III sind bekannt.The starting materials of the formula III are known.

Als säurebindende Mittel kommen beispielsweise in Frage Basen wie Triäthylamin, N-Athylmorpholin, Pyridin, Chinolin, Alkali-, Erdalkali-carbonate, -bicarbonate.Bases such as, for example, can be used as acid-binding agents Triethylamine, N-ethylmorpholine, pyridine, quinoline, alkali, alkaline earth carbonates, -bicarbonates.

Die Herstellung wird vorteilhaft in einem Lösungs- oder -Verteilungsmittel durchgeführt. Als Lösungs- oder Verteilungsmittel kommen beispielsweise in Frage Alkohole, wie Methanol, Äthanol, Propanol, Butanol, Methoxyäthanol, Äthoxyäthanol, Ketone wie Aceton, Methyläthylketon, Diäthylketon, Methylisobutylketon, Amide wie Dimethylformamid, Dimethylacetamid, N-Methylpyrrolidon, Tetramethylharnstoff, Hexamethylphosphorsäuretriamid, Äther wie Dipropyläther, Dibutyläther, Äthylenglycoldimethyläther, -diäthyläther, Diäthylenglycoldimethyläther, Tetrahydrofuran, Dioxan, gegebenenfalls chlorierte, aliphatische und aromatische Kohlenwasserstoffe, wie Methylenchlorid, Chlorcform, Dichloräthan, Tetrachloräthan, Benzol, Toluol, Xylol, Chlorbenzol, Dichlorbenzol, ferner Dimethylsulfoxid, Tetramethylensulfon, Acetonitril.The preparation is advantageously carried out in a solvent or dispersant carried out. Examples of suitable solvents or distributing agents are Alcohols such as methanol, ethanol, propanol, butanol, methoxyethanol, ethoxyethanol, Ketones such as acetone, methyl ethyl ketone, diethyl ketone, methyl isobutyl ketone, amides such as Dimethylformamide, dimethylacetamide, N-methylpyrrolidone, tetramethylurea, hexamethylphosphoric acid triamide, Ethers such as dipropyl ether, dibutyl ether, ethylene glycol dimethyl ether, diethyl ether, Diethylene glycol dimethyl ether, tetrahydrofuran, dioxane, optionally chlorinated, aliphatic and aromatic hydrocarbons, such as methylene chloride, chloroform, Dichloroethane, tetrachloroethane, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, also dimethyl sulfoxide, tetramethylene sulfone, acetonitrile.

Die Reaktionszeiten betragen wenige Minuten bis einige Stunden. Die Reaktionstemperaturen liegen zwischen o und 1000C,vorteilhaft zwischen 60 und 80°C.The reaction times are a few minutes to a few hours. the Reaction temperatures are between 0 and 1000C, advantageously between 60 and 80.degree.

Die Herstellung der Verbindungen der Formel I nach Verfahren b) wird durch Umsetzung eines Reduktionsmittels mit einem Anthrachinon-d.icarbonsäureamid der Formel IV durchgeführt.The preparation of the compounds of formula I by process b) is by reacting a reducing agent with an anthraquinone-dicarboxamide of formula IV carried out.

Als Ausgangsstoffe der Formel IV kommen beispielsweise in Frage Anthrachinon-2,6-, bzw. -2,7-dicarbonsäureamide des Ammoniak, Dimethylamin, Diäthylamin, Dipropylamin, Diisopropyllmin, Dibutylamin, Diisobutylamin, Methyl- äthylamin, Methylpropylamin, Methybutylamin, Pyrrolidin, 2-Methyl-pyrrolidin, 2,5-Dimethyl-pyrrolidin, Piperidin, 2-Methyl-piperidin, 2,6-Dimethyl-piperidin, 3-Methylpiperidin, 4-Methyl-piperidin, 4-Dimethylamino-piperidin, 4-Piperidino-piperidin, Morpholin, 2-Methyl-morpholin, 2,6-Dimethyl-morpholin, Piperazin, N-Methyl-piperazin, N-Athyl-piperazin, N-Propyl-piperazin, N-Butyl-pipen-izi n, N-2-Hydroxyäthyl-piperazin, N-3-Hydroxypropyl-piperazin, N-Methyl-hexahydropyrimidin, N-Methyl-homopiperazin, Hexamethylenimin und Thiomorpholin.As starting materials of the formula IV, for example, anthraquinone-2,6-, or -2,7-dicarboxamides of ammonia, dimethylamine, diethylamine, dipropylamine, Diisopropylamine, dibutylamine, diisobutylamine, methyl- ethylamine, Methylpropylamine, methybutylamine, pyrrolidine, 2-methyl-pyrrolidine, 2,5-dimethyl-pyrrolidine, Piperidine, 2-methyl-piperidine, 2,6-dimethyl-piperidine, 3-methylpiperidine, 4-methyl-piperidine, 4-dimethylamino-piperidine, 4-piperidino-piperidine, morpholine, 2-methyl-morpholine, 2,6-dimethyl-morpholine, piperazine, N-methyl-piperazine, N-ethyl-piperazine, N-propyl-piperazine, N-butyl-pipen-izi n, N-2-hydroxyethyl-piperazine, N-3-hydroxypropyl-piperazine, N-methyl-hexahydropyrimidine, N-methyl-homopiperazine, hexamethyleneimine and thiomorpholine.

Die Ausgangsstoffe der Formel IV können erhalten werden ---durch Umsetzung von Anthrachinon-2,6- bzw. -2,7-dicarbonsäureester oder Anthrachinon-2,6-, bzw -2, 7-dicarbon -säurechloride mit entsprechenden Aminen. The starting materials of the formula IV can be obtained through --- Conversion of anthraquinone-2,6- or -2,7-dicarboxylic acid ester or anthraquinone-2,6-, or -2, 7-dicarboxylic acid chlorides with corresponding amines.

Die den Anthrachinon-2,6- bzw. -2,7-carbonsäurederivaten zugrunde liegenden Carbonsäuren können nach US-Patent 3 939 276 durch Oxydation von 2,7- bzw. 2,7-Dimethylanthrachinon mittels Chromsäure erhalten werden. The basis of the anthraquinone-2,6- or -2,7-carboxylic acid derivatives lying carboxylic acids can according to US Patent 3,939,276 by oxidation of 2.7- and 2,7-dimethylanthraquinone can be obtained by means of chromic acid.

Als Reduktionsmittel kommen vorzugsweise in Frage Metallhydride, wie Lithiumaluminiumhydrid oder Natriumaluminiumbisalkoxydihydrid. Die Metallhydride werden in äquivalenten Mengen angewendet. Z.B. auf 1 Mol Anthrawchinon-dicarbonsäureamid der Formel IV 1,5 Mol Lithiumalanat. Vorteilhafterweise empfiehlt sich jedoch die Anwendung eines Überschusses an Reduktionsmittel bis 100% Die Reduktionen werden vorteilhaft in einem Lösungs- oder Verteilungsmittel durchgeführt. Als Lösungs- oder Verteilungsmittel kommen beispielsweise in Frage Äther wie -Diäthyläther, Dipropyläther, Dibutyläther, Äthylenglycoldimethyläther, -diäthyläther, Diäthylenglycoldimethyläther, Tetrahydrofuran, Dioxan. Als Lösungsvermittler können manchmal mit Vorteil Pyridin oder N-Äthylmorpholin zugesetzt werden. Metal hydrides are preferably used as reducing agents, such as lithium aluminum hydride or sodium aluminum bisalkoxydihydride. The metal hydrides are used in equivalent amounts. E.g. to 1 mole of anthrawquinone dicarboxamide of formula IV 1.5 moles of lithium alanate. Advantageously, however, is recommended Use of an excess of reducing agent up to 100% The reductions are advantageously carried out in a solvent or distribution medium. As a solution or distribution agents are, for example, ethers such as diethyl ether, dipropyl ether, Dibutyl ether, ethylene glycol dimethyl ether, diethyl ether, diethylene glycol dimethyl ether, Tetrahydrofuran, dioxane. Pyridine can sometimes be used as a solubilizer or N-ethylmorpholine can be added.

Die Reduktionszeiten betragen wenige Minuten bis einige Stunden. Die Reduktionstemperaturen liegen zwischen 0 und 1000C, vorteilhaft zwischen 25 und 600C.The reduction times are a few minutes to a few hours. the Reduction temperatures are between 0 and 1000C, advantageously between 25 and 600C.

Die nach der Reduktion der Anthrachinon-dicarbonsäureamide der Formel IV als Zwischenprodukte anfallenden Anthrahydrochinone werden durch Behandeln mit einem Oxydationsmi t.L.el in Anthrachinon-Derivate der Formel I umgewandelt.After the reduction of the anthraquinone dicarboxamides of the formula IV anthrahydroquinones obtained as intermediates are treated with an Oxydationsmi t.L.el converted into anthraquinone derivatives of the formula I.

Als Oxydationsmittel wird vorteilhafterweise Luftsauerstoff verwendet. Zur Oxydation wird- zweckmäßig durch eine wässrige oder alkoholisch-wässrige Suspension des Anthranydrochir.ons Luft geleitet.Atmospheric oxygen is advantageously used as the oxidizing agent. An aqueous or alcoholic-aqueous suspension is expediently used for the oxidation of the Anthranydrochir.ons air.

Die Isolierung der Verbindungen der Formel I, wie sie nach Verfahren a) oder b) erhalten werden, erfolgt nach üblichen Methoden durch Abdestillieren der verwendeten Lösungsmittel oder durch Verdünnen der Reaktionslösung mit Wasser und Absaugen des Endprodukts.The isolation of the compounds of formula I as they are by method a) or b) are obtained, is carried out by customary methods by distilling off the solvents used or by diluting the reaction solution with water and aspirating the end product.

Gegenbenenfalls kann eine Reinigung der Endprodukte durch Umkristallisieren aus einem geeigneten Lösungsmittel wie Äthanol, Isopropanol oder Glykolmonomethyläther oder Lösut silil ttelgeiiiiscli wie Dimethy lformamid mit einem der vorgenannten erfolgen.If necessary, the end products can be purified by recrystallization from a suitable solvent such as ethanol, isopropanol or glycol monomethyl ether or Lösut silil ttelgeiiiiscli such as dimethylformamide with one of the aforementioned take place.

Die neuen Verbindungen der Formel I können gegebenenfalls durch Zusetzen einer physiologisch verträglichen Säure in das entsprechende Salz übergeführt werden. Als physiologisch vcrträgliche Säuren kommen beispielsweise in Frage Halogenwasserstoffsäuren, insbesondere Salzsäure, ferner Schwefelsäure, Phosphorsäure, Essigsäure, Milchsäure oder Weinsäure.The new compounds of the formula I can, if appropriate, by adding a physiologically acceptable acid can be converted into the corresponding salt. Suitable physiologically compatible acids are, for example, hydrohalic acids, in particular hydrochloric acid, also sulfuric acid, phosphoric acid, acetic acid, lactic acid or tartaric acid.

Die Bis-Aminomethylanthrachinon-Derivate der Formel I sind gut verträglich und eignen sich zur Bekämpfung von Protozoenerkrankungen bei Mensch und Tier, insbesondern der Amöbiasis, die durch Infektionen mit Entamoeba histolytica hervorgerufen wird. Außerdem entfalten die neuen Verbindungen eine direkte oder durch ihre inter- feroninduzierende Eigenschaft indirekte Wirkung gegen Influenza- und Encephalomyocarditis-Viren. Durch ihre interfcron-induzierende Wirkung sind sie geeiqnct zur Bekämpfung von Virus- und Krebserkrankungen.The bis-aminomethylanthraquinone derivatives of the formula I are well tolerated and are particularly suitable for combating protozoal diseases in humans and animals the amebiasis caused by infections with Entamoeba histolytica. In addition, the new connections develop a direct or through their inter- feron-inducing Property indirect action against influenza and encephalomyocarditis viruses. By their interfcron-inducing effect, they are suitable for combating virus and cancers.

Die Anwendung der neuen Verbindungen kann oral parenteral oder lokal erfolgen, z.B. nasal bei der Behandlung der lnfluenza. The application of the new compounds can be oral, parenteral or topical for example, nasally in the treatment of influenza.

Die orale Anwendung erfolgt in pharmazeutisch üblichen Zubereitungen, z.B. in Form von Tabletten oder Kapseln, die pro Tagesdosis etwa 10 bis 1000 mg des Wirkstoffes in Mischung mit einem gebräuchlichen Trägerstoff und/oder Konstituens enthalten. Die parenterale Anwendung erfolgt in Form von Lösungen, insbesondere in Wasser oder physiologischer Kochsalzlösung. Oral use takes place in conventional pharmaceutical preparations, e.g. in the form of tablets or capsules, which contain about 10 to 1000 mg per daily dose of the active ingredient in a mixture with a customary carrier and / or constituent contain. Parenteral use is in the form of solutions, in particular in water or physiological saline solution.

Die nasale Anwendung erfolgt in Form von Sprays, bei welchen eine-geeignete Lösung des Verfahrenserzeugnis£;es, z.B. die wäßrige Lösung eines Hydrochlorids, durch ein Treibmittel fein zerstäubt wird. The nasal application takes place in the form of sprays, in which a-suitable Solution of the product of the process; it, e.g. the aqueous solution of a hydrochloride, is finely atomized by a propellant.

Herstellungsbeispiele: Beispiel 1 (Verfahren a)) 2,6-Bis-(N-Methylpiperazinomethyl)-anthrachinon-9L10 39,4 g (0,1 Mol) 2,6-Bis-Brommethyl-anthrachinon-9,10 (Fp. 3160C) werden in 500 ml Äthanol suspendiert, 44 g (0,44 Mol) N-Methylpiperazin werden zugegeben und die Reaktionsmischung 1,5 Stunden unter Rückfluß erhitzt.Manufacturing examples: Example 1 (method a) 2,6-bis (N-methylpiperazinomethyl) anthraquinone-9L10 39.4 g (0.1 mol) of 2,6-bis-bromomethyl-anthraquinone-9.10 (melting point 3160C) are in 500 ml of ethanol suspended, 44 g (0.44 mol) of N-methylpiperazine are added and the The reaction mixture was refluxed for 1.5 hours.

Dabei geht 2,6-Bis-Brommethyl-anthrachinon-9,10 in Lösung.2,6-bis-bromomethyl-anthraquinone-9,10 goes into solution.

Danach wird die Lösung unter vermindertem Druck zur Trockene eingedampft, der feste Rückstand mit Wasser angerührt, abfiltriert, mit Wasser gewaschen und aus Äthanol unter Zusatz von Aktivkohle umkristallisiert.The solution is then evaporated to dryness under reduced pressure, the solid residue is stirred with water, filtered off, washed with water and recrystallized from ethanol with the addition of activated charcoal.

Man erhält so 33 g (76 % der Theorie), 2,6-Bis-(N-piperazinomethyl) -anthrachinon-9, 10 in Form von gelblichen Kristallen vom Fp. 2020C.This gives 33 g (76% of theory), 2,6-bis (N-piperazinomethyl) -anthraquinone-9, 10 in the form of yellowish crystals of melting point 2020C.

Das als Ausgangsstoff verwendete 2,6-Bis-Brommethylanthrachinon-9,10 erhält man durch Umsetzung von 2,6-Dimethyl-anthrachinon-9,10 mit N-Bromsuccinimid in 80%iger Ausbeute in Form von gelben Kristallen mit einem Fp. 3160C (Zersetzung).The 2,6-bis-bromomethylanthraquinone-9,10 used as starting material obtained by reacting 2,6-dimethyl-anthraquinone-9,10 with N-bromosuccinimide in 80% yield in the form of yellow crystals with a melting point of 3160C (decomposition).

Anal.og erhält man aus 2,7-Dimethyl-anthrachinon-9,10 mit N-Bromsuccinimid, 2,7-Bis-Brommethyl-anthrachinon-9,10 vom Fp. 265 0C.Similarly, from 2,7-dimethyl-anthraquinone-9,10 with N-bromosuccinimide, 2,7-bis-bromomethyl-anthraquinone-9.10 of m.p. 265 ° C.

Nach dem in Beispiel 1 beschriebenen Verfahren können durch Umsetzung von 2,6-Bis-Brommethyl-anthrachinon-9,10 und entsprechenden Aminen der Formel III erhalten werden: 2,6-Bis-(Aminomethyl)-anthrachinon-9,10x2HCl , Fp 3000C 2,6-Bis-(Dimethylaminomethyl)-anthrachinon-9,10x2HCl Fp. 3000C, Base 1550C 2,6-Bis-(Diäthylaminomethyl)-anthrachinon-9,10 Fp.94°C 2,6-Bis- (Dipropylaminomethyl)-anthrachinon-9, 10 Fp. 400C 2,6-Bis-(Dibutylaminomethyl)-anthrachinon-9,10 Oel 2, 6-Bis- (Methyläthylaminomethyl) -anthrachinon-9, 10 2,6-Bis-(Pyrrolidinomethyl)-anthrachinon-9,10 Fp.156°C 2,6-Bis-(2,5-Dimethylpyrrolidinomethyl)-anthrachinon-9,10 2,6-Bis-(Piperidinomethyl)-anthrachinon-9,10 Fp.184°C 2,6-Bis-(2-Methylpiperidinomethyl)-anthrachinon-9,10 Fp.193°C 2,6-Bis-(2,6-Dimethylpiperidinomethyl)-anthrachinon-9,10 Fp.160°C 2,6-Bis-(Morpholinomethyl)-anthrachinon-9,10 Fp.224°C 2,6-Bis-(2,6-Dimethylmorpholinomethyl)-anthrachinon-9,10 2,6-Bis-(4-Piperidinopiperidinomethyl-anthrachinon-9,10 Fp.181°C 2,6-Bis-(N-Äthylpiperazinomethyl)-anthrachinon-9,10 Fp.165°C 2,6-Bis- (N-2-Hydroxyäthylpiperazinomethyl) -anthrachinon-9,10 Fp.168°C 2,6-Bis-(N-Methylhomopiperazinomethyl)-anthrachinon-9,10 Fp.200°C 2,6-Bis- (Hexamethyleniminsmethyl) -anthrachinon-9, 10 Fp. 186 0C Nach dem in Beispiel 1 beschriebenen Verfahren können durch Umsetzung von 2, 7-Bis-Brommethyl-anthrachinon-9, 10 und entsprechenden Aminen der Formel III erhalten werden: 2, 7-Bis- (Aminomethyl) -anthrachinon-9, 10 2,7-Bis-(Dimethylaminomethyl)-anthrachinon-9,10 Fp.96°C 2,7-Bis-(Diäthylaminomethyl)-anthrachinon-9,10 Fp.68°C 2,7-Bis- (Dipropylaminomethyl)-anthrachinon-9, 10 Oel 2,7-Bis-(Dibutylaminomethyl)-anthrachinon-9,10 2,7-Bis- (Methyläthylaminomethyl) -anthrachinon-9 , 10 2, 7-Bis- (Pyrrolidinomethyl) -anthrachinon-9 ,10 Fp. 1200C 2,7-Bis- (2, 5-Dimethylpyrrolidinomethyl) -anthrachinon-9, 10 2,7-Bis-(Piperidinomethyl)-anthrachinon-9,10 Fp.166°C 2,7-Bis-(2-Methylpiperidinomethyl)-anthrachinon-9,10 2,7-Bis-(2,6-Dimethylpiperidinomethyl)-anthrachinon-9,10 2,7-Bis-(4-piperidinopiperidinomethyl)-anthrachinon-9,10 Fp.167°C 2,7-Bis-(Morpholinomethyl)-anthrachinon-9,10 Fp.190°C 2,7-Bis-(2,6-Dimethylmorpholinomethyl)-anthrachinon-9,10 2,7-Bis-(N-Methyliperazinomethyl)-anthrachinon-9,10 Fp.138°C 2,7-Bis-(N-Äthylpiperazinomethyl)-anthrachinon-9,10 Fp.120°C 2,7-Bis- (N- 2-Hydroxyäthylpiperazinomethyl) -anthrachinon-9,10 Fp.1090C 2,7-Bis-(N-Methylhomopiperazinomethyl)-anthrachinon-9,10 2,7-Bis-(Hexamethyleniminomethyl)-anthrachinon-9,10 Beispiel 2 (Verfahren b)) 2,6-Bis-(N-Methylpiperazinomethyl)-anthrachinon-9,10 4,6 g (0,01 Mcl) Anthrachinon-9,10-dicarbonsäure-2,6-bis-(N-methylpiperazid) werden in 100 ml trockenem Tctrahydrofuran suspendiert. Unter Rühren und Temperaturen von 30-40°C (Kühlung) werden portionsweise 1,14 g (0,03 Mol = 100 % überschuß) Lithiumaluminiumhydrid suspendiert in 50 ml Tetrahydrofuran eingetragen. Nach erfolger Reaktion wird noch 3 Stunden unter Rühren auf 40-500C erwärmt. Nach dem Abkühlen wird der Ansatz durch Zutropfen von Wasser unter Rühren und Kühlen hydrolysiert, die Lithiumaluminiumhydroxyde durch Absaugen abgetrennt, mit Tetrahydrofuran mehrfach gut gewaschen, die wässrige Tetrahydrofuranlösung unter kräftigem Durchleiten von Luft eingeengt. Dabei fällt das Endprodukt aus. Die Ausfällung wird durch Zugabe von Wasser vervollständigt, abgesaugt und aus Äthanol unter Kohlezusatz umkristallisiert. Man erhält so 2,6-Bis-(N-Methylpiperazinomethyl)-anthrachinon-9,10 in guter Ausbeute vom Fp. 202°C. Es ist identisch mit dem nach Verfahren a) Beispiel 1 erhaltenen Endprodukt.According to the method described in Example 1, by reaction of 2,6-bis-bromomethyl-anthraquinone-9,10 and corresponding amines of the formula III the following are obtained: 2,6-bis- (aminomethyl) -anthraquinone-9.10x2HCl, mp 3000C 2,6-bis- (dimethylaminomethyl) -anthraquinone-9.10x2HCl M.p. 3000C, base 1550C 2,6-bis (diethylaminomethyl) anthraquinone-9.10 M.p. 94 ° C 2,6-bis- (dipropylaminomethyl) -anthraquinone-9.10. M.p. 400C 2,6-bis- (dibutylaminomethyl) -anthraquinone-9.10 Oil 2,6-bis (methylethylaminomethyl) -anthraquinone-9, 10 2,6-bis- (pyrrolidinomethyl) -anthraquinone-9,10 Mp 156 ° C 2,6-bis- (2,5-dimethylpyrrolidinomethyl) -anthraquinone-9.10 2,6-bis- (piperidinomethyl) -anthraquinone-9.10 M.p. 184 ° C 2,6-bis- (2-methylpiperidinomethyl) -anthraquinone-9.10 M.p. 193 ° C 2,6-bis- (2,6-dimethylpiperidinomethyl) -anthraquinone-9.10 Mp 160 ° C 2,6-bis- (morpholinomethyl) -anthraquinone-9.10. Mp 224 ° C 2,6-bis- (2,6-dimethylmorpholinomethyl) -anthraquinone-9.10 2,6-bis- (4-piperidinopiperidinomethyl-anthraquinone-9.10 m.p. 181 ° C 2,6-bis- (N -ethylpiperazinomethyl) -anthraquinone-9.10 M.p. 165 ° C 2,6-bis (N-2-hydroxyethylpiperazinomethyl) anthraquinone-9.10 m.p. 168 ° C 2,6-bis- (N-methylhomopiperazinomethyl) -anthraquinone-9.10 mp 200 ° C 2,6-bis- (hexamethyleneiminesmethyl) -anthraquinone-9, 10 m.p. 186 0C According to the method described in Example 1 can by reacting 2, 7-bis-bromomethyl-anthraquinone-9, 10 and corresponding amines of the formula III are obtained: 2,7-bis (aminomethyl) anthraquinone-9, 10 2,7-bis (dimethylaminomethyl) anthraquinone-9,10 Mp 96 ° C 2,7-bis (diethylaminomethyl) anthraquinone-9.10 m.p. 68 ° C 2,7-bis (dipropylaminomethyl) -anthraquinone-9, 10 oil 2,7-bis- (dibutylaminomethyl) -anthraquinone-9,10 2,7-bis- (methylethylaminomethyl) -anthraquinone-9, 10 2, 7-bis (pyrrolidinomethyl) -anthraquinone-9, 10 m.p. 1200C 2,7-bis- (2,5-dimethylpyrrolidinomethyl) -anthraquinone-9, 10 2,7-bis- (piperidinomethyl) -anthraquinone-9.10 Mp 166 ° C 2,7-bis- (2-methylpiperidinomethyl) -anthraquinone-9.10 2,7-bis- (2,6-dimethylpiperidinomethyl) -anthraquinone-9.10 2,7-bis- (4-piperidinopiperidinomethyl) -anthraquinone-9.10 m.p. 167 ° C 2,7-bis- (morpholinomethyl) -anthraquinone-9.10 Mp 190 ° C 2,7-bis- (2,6-dimethylmorpholinomethyl) -anthraquinone-9.10 2,7-bis (N-methyliperazinomethyl) anthraquinone-9.10 Mp 138 ° C 2,7-bis (N-ethylpiperazinomethyl) -anthraquinone-9.10 m.p. 120 ° C 2,7-bis (N- 2-hydroxyethylpiperazinomethyl) anthraquinone-9.10 m.p. 1090C 2,7-bis (N-methylhomopiperazinomethyl) anthraquinone-9.10 2,7-bis- (hexamethyleneiminomethyl) -anthraquinone-9.10 Example 2 (method b)) 2,6-bis- (N-methylpiperazinomethyl) -anthraquinone-9.10 4.6 g (0.01 Mcl) of anthraquinone-9,10-dicarboxylic acid-2,6-bis- (N-methylpiperazide) suspended in 100 ml of dry tetrahydrofuran. With stirring and temperatures of 30-40 ° C (cooling) 1.14 g (0.03 mol = 100% excess) lithium aluminum hydride are added in portions suspended in 50 ml of tetrahydrofuran. After a successful reaction, will still be Heated to 40-500C for 3 hours while stirring. After cooling, the approach is through Dropwise addition of water with stirring and cooling hydrolyzes the lithium aluminum hydroxides separated by suction, washed well several times with tetrahydrofuran, the aqueous Tetrahydrofuran solution concentrated while vigorously passing air through. It falls the end product. The precipitation is completed by adding water, suctioned off and recrystallized from ethanol with the addition of charcoal. This gives 2,6-bis (N-methylpiperazinomethyl) anthraquinone-9,10 in good yield of melting point 202 ° C. It is identical to the example according to method a) 1 final product obtained.

Das als Ausgangsstoff verwendete Anthrachinon-9, 1 0-dicarbonsäure-2,6-bis-(N-Methylpiperazid) vom Fp.248°C (Umwandlungspunkt Fp.226°C) erhält man durch Umsetzung von Anthrachinon-9,10-dicarbonsäurechlorid-2,6 vom Fp.210°C mit N-Methylpipera zid.The anthraquinone-9, 10-dicarboxylic acid-2,6-bis- (N-methylpiperazide) used as starting material with a melting point of 248 ° C. (conversion point, melting point 226 ° C.) is obtained by reacting anthraquinone-9,10-dicarboxylic acid chloride-2,6 of m.p. 210 ° C with N-Methylpipera zid.

In analoger Weise wird durch Reduktion mit Lithiumaluminiumhydrid aus Anthrachinon-9,10-dicarbonsäure-2,7-bis-(N-Methylpiperazid) Fp. 1450C (aus Ant}rachi.non-9,10-dicarbonsäurechlorid-2,7 Fp.188°C und N-Methylpiperazin) 2,7-Bis-(N-Methylpiperazinomethyl)-anthrachinon-9,10 vom Fp.138°C in guter Ausbeute gewonnen.In an analogous manner, by reduction with lithium aluminum hydride from anthraquinone-9,10-dicarboxylic acid-2,7-bis (N-methylpiperazide) m.p. 1450C (from anthraquinone-9,10-dicarboxylic acid chloride-2,7 M.p. 188 ° C and N-methylpiperazine) 2,7-bis (N-methylpiperazinomethyl) -anthraquinone-9.10 obtained in good yield with a melting point of 138 ° C.

Claims (5)

PATENTANSPRÜCHE 1. Bis-Aminomethyl-anthrachinon-Derivate der Formel I und ihre Salze mit physiologisch verträglichen Säuren, worin R1 und R2 gleich oder verschieden sind und Wasserstoff, geradkettiges oder verzweigtes Alkyl mit ein bis vier Kohlenstoffatomen, oder 1 und R2 zusammen eine Alkylenkette mit vicr, fünf oder sechs Kohlenstoffatomen, die mit dem Stickstoffatom einen fünf-, sechs- oder siebengliedrigen heterocyclischen Ring bilden, der ein weiteres Heteroatom aus der Gruppe Stickstoff, Sauerstoff und Schwefel enthalten kann und seinerseits durch geradkettiges oder verzweigtes Alkyl mit ein bis vier Kohlenstoffatomen substituiert sein kann, bedeuten.PATENT CLAIMS 1. Bis-aminomethyl-anthraquinone derivatives of the formula I. and their salts with physiologically acceptable acids, in which R1 and R2 are identical or different and are hydrogen, straight-chain or branched alkyl with one to four carbon atoms, or 1 and R2 together form an alkylene chain with vicr, five or six carbon atoms, which with the nitrogen atom a five - Form, six- or seven-membered heterocyclic ring which can contain a further heteroatom from the group consisting of nitrogen, oxygen and sulfur and which in turn can be substituted by straight-chain or branched alkyl having one to four carbon atoms. 2. Verfahren zur Herstellung von Bis-Aminomethyl-anthrachinon-Derivaten der Formel I in Anspruch 1 sowie von deren Salzen, dadurch gekennzeichnet, daß man a) ein substituitertes Dimethyl-anthrachinon der Formel II worin Y ein Halogenatom wie Chlor, Brom, Jod, eine Acyloxygruppe oder eine Arylsulfonyloxygruppe bedeutet, mit einem Amin der Formel III worin R1 und R2 die zu Formel I erwähnten Bedeutungen haben, umsetzt und gegebenenfalls durch Zugabe einer physiologisch verträglichen Säure in ein Salz überführt, oder b) ein Anthrachinon-dicarbonsäureamid der Formel IV worin R1 und R2 die zu Formel I erwähnten Bedeutungen haben, reduziert und die als Zwischenprodukt erhaltenen Anthrahydrochinon-Derivate zu Anthrachinon-Derivaten der Formel 1 oxydiert und gegebenenfalls durch Zugabe einer physiologisch verträglichen Säure in ein Salz überführt.2. Process for the preparation of bis-aminomethyl-anthraquinone derivatives of the formula I in claim 1 and of their salts, characterized in that a) a substituted dimethyl-anthraquinone of the formula II wherein Y is a halogen atom such as chlorine, bromine, iodine, an acyloxy group or an arylsulfonyloxy group, with an amine of the formula III in which R1 and R2 have the meanings mentioned for formula I, are converted and optionally converted into a salt by adding a physiologically acceptable acid, or b) an anthraquinone dicarboxamide of the formula IV in which R1 and R2 have the meanings mentioned for formula I, and the anthrahydroquinone derivatives obtained as an intermediate are oxidized to anthraquinone derivatives of the formula 1 and optionally converted into a salt by adding a physiologically acceptable acid. 3. Arzneimittel, gekennzeichnet durch einen Gehalt an einem Bis-Aminomethylanthrachinonderivat der Formel I in Anspruch 1.3. Medicaments, characterized in that they contain a bis-aminomethylanthraquinone derivative of formula I in claim 1. 4. Verwendung von einem Bis-Aminomethylanthrachinonderivat der Formel I in Anspruch 1 zur Behandlung von Protozoen-, Virus- oder Krebserkrankungen.4. Use of a bis-aminomethylanthraquinone derivative of the formula I in claim 1 for the treatment of protozoal, viral or cancer diseases. 5. Verwendung von einem Bis-Antinomethylanthrachinonderivat der Formel I in Anspruch 1 zur Herstellung eines Arzneimittels gegen Protozoen-, Virus- oder Krebserkrankungen.5. Use of a bis-antinomethylanthraquinone derivative of the formula I in claim 1 for the preparation of a medicament against protozoal, virus or Cancers.
DE19803044072 1980-11-24 1980-11-24 Bis-aminomethyl-anthraquinone derivs. - with antiprotozoal, antiviral and interferon inducing activity Withdrawn DE3044072A1 (en)

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Application Number Priority Date Filing Date Title
DE19803044072 DE3044072A1 (en) 1980-11-24 1980-11-24 Bis-aminomethyl-anthraquinone derivs. - with antiprotozoal, antiviral and interferon inducing activity
EP81109738A EP0052853A1 (en) 1980-11-24 1981-11-17 Bis-aminomethyl-anthraquinone derivatives, process for their manufacture, compositions containing them and their use
ES507234A ES507234A0 (en) 1980-11-24 1981-11-18 PROCEDURE FOR THE PREPARATION OF DERIVATIVES OF BIS-AMINO-METHYL-ANTHRAQUINONE.
GR66570A GR78224B (en) 1980-11-24 1981-11-19
JP56185574A JPS57118540A (en) 1980-11-24 1981-11-20 Bis-aminomethyl-anthraquinone derivative
FI813709A FI813709L (en) 1980-11-24 1981-11-20 BIS-AMINOMETHYLTRAKINONDERIVAT FOERFARANDEN FOER DERAS FRAMSTAELLNING DESSA INNEHAOLLANDE LAEKEMEDEL OCH DERAS ANVAENDNING
IL64336A IL64336A0 (en) 1980-11-24 1981-11-22 Bis-aminomethyl-anthraquinone derivatives,a process for their preparation,agents containing them and their use
ZA818107A ZA818107B (en) 1980-11-24 1981-11-23 Bis-aminomethyl-anthraquinone derivatives,a process for their preparation,agents containing them and their use
DK519581A DK519581A (en) 1980-11-24 1981-11-23 BIS-AMINOMETHYL-ANTRAQUINON DERIVATIVES OF THEIR PREPARATION AND USE
PT74023A PT74023B (en) 1980-11-24 1981-11-23 BIS-AMINOMETHYL ANTHRACINE DERIVATIVES METHOD FOR THE MANUFACTURE THEREOF AND THEIR USE
NO813974A NO813974L (en) 1980-11-24 1981-11-23 BIS-AMINOMETHYL-ANTRAKINON DERIVATIVES, PROCEDURES FOR THEIR PREPARATION, MATERIALS CONTAINING THESE AND THEIR USE
KR1019810004526A KR830007489A (en) 1980-11-24 1981-11-23 Method for preparing bis-aminomethyl-anthraquinone derivatives
AR287543A AR227341A1 (en) 1980-11-24 1981-11-23 PROCEDURE FOR PREPARING DERIVATIVES OF BIS-AMINOMETHYL-ANTHRAQUINONE
AU77766/81A AU7776681A (en) 1980-11-24 1981-11-23 Bisaminomethyl-anthraquinone derivatives
ES516225A ES8306734A1 (en) 1980-11-24 1982-10-05 Bis-aminomethyl-anthraquinone derivatives, process for their manufacture, compositions containing them and their use.

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19803044072 DE3044072A1 (en) 1980-11-24 1980-11-24 Bis-aminomethyl-anthraquinone derivs. - with antiprotozoal, antiviral and interferon inducing activity

Publications (1)

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DE3044072A1 true DE3044072A1 (en) 1982-07-15

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DE19803044072 Withdrawn DE3044072A1 (en) 1980-11-24 1980-11-24 Bis-aminomethyl-anthraquinone derivs. - with antiprotozoal, antiviral and interferon inducing activity

Country Status (4)

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JP (1) JPS57118540A (en)
KR (1) KR830007489A (en)
DE (1) DE3044072A1 (en)
ZA (1) ZA818107B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101730531A (en) * 2007-05-10 2010-06-09 阿瓦隆药品公司 derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine and uses thereof
WO2016116527A1 (en) * 2015-01-20 2016-07-28 Cynora Gmbh Organic molecules, in particular for use in optoelectronic components

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101730531A (en) * 2007-05-10 2010-06-09 阿瓦隆药品公司 derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine and uses thereof
CN108314663A (en) * 2007-05-10 2018-07-24 多格伍德药品公司 The derivative and application thereof of fluorenes, anthracene, xanthene, Dibenzosuberone and acridine
CN108314663B (en) * 2007-05-10 2022-05-13 多格伍德药品公司 Derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine and uses thereof
WO2016116527A1 (en) * 2015-01-20 2016-07-28 Cynora Gmbh Organic molecules, in particular for use in optoelectronic components

Also Published As

Publication number Publication date
KR830007489A (en) 1983-10-21
JPS57118540A (en) 1982-07-23
ZA818107B (en) 1982-10-27

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