DE2922488A1 - 2-Hydroxy-4-amino-6-methyl-isophthalic acid - and 2,6-di:acetyl-3-hydroxy-5-methylphenol derivs. with cardiovascular activity - Google Patents

2-Hydroxy-4-amino-6-methyl-isophthalic acid - and 2,6-di:acetyl-3-hydroxy-5-methylphenol derivs. with cardiovascular activity

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DE2922488A1
DE2922488A1 DE19792922488 DE2922488A DE2922488A1 DE 2922488 A1 DE2922488 A1 DE 2922488A1 DE 19792922488 DE19792922488 DE 19792922488 DE 2922488 A DE2922488 A DE 2922488A DE 2922488 A1 DE2922488 A1 DE 2922488A1
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methyl
hydroxy
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alkyl
phenyl
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Fritz Prof Dr Eiden
Hans-Perer Leister
Dieter Prof Dipl Chem Dr Mayer
Ernst-Guenther Dr Teupe
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THIEMANN CHEM PHARM FAB
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

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

Abstract

New 2-hydroxy-4-methylbenzene derivs. are cpds. of formula (I) and their acid addn. salts. In (I):- each R1 (identical) is CH3 or 1-4C alkoxy; R3 and R3 are 1-4C alkyl or NR2R3 is pyrrolidino, piperidino, 4-cyano-4-methyl-1,4-diazepino, morpholino, di(1-4C alkyl) morpholino, 1,2,3,4-tetrahydro-isoquinolino, or 4-R6-piperazin-1-yl in which R6 is 1-4C alkyl, 2-hydroxyethyl, phenyl, (1-4C alkyl) phenyl; (1-4C alkoxy)phenyl, halophenyl or trifluoromethylphenyl; and R4 is H, CH3 or C2H5. (I) ahve cardiovascular activity. They are also useful as intermediates for 3-(2-pyrazolyl)-4-amino-2-hydroxyacetophenone derivs. with cardiovascular activity.

Description

2-Hydroxy-4-methyl-benzolverbindungen, Verfahren zu2-Hydroxy-4-methyl-benzene compounds, method too

ihrer Herstellung und ihre Verwendung Die Erfindung betrifft neue 2-Hydroxy-4-methyl-benzolverbindungen, die als Arzneimittel geeignet sind.their manufacture and use The invention relates to new 2-hydroxy-4-methyl-benzene compounds that are suitable as pharmaceuticals are.

Die Erfindung ist in den Patentansprüchen definiert.The invention is defined in the claims.

Die Reste R2 und R3 können gleich oder verschieden sein.The radicals R2 and R3 can be identical or different.

R2, R3 und R5 können Methyl, Athyl, n-Propyl, i-Propyl, n-Butyl, i-Butyl oder t-Butyl bedeuten und sind vorzugsweise Methyl oder Methyl.R2, R3 and R5 can be methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl or t-butyl and are preferably methyl or methyl.

Wenn R2 + R3 + N C1- - bis C4-Dialkyl-morpholino bedeuten, so ist Dimethylmorpholino, insbesondere 2,6-Dimethylmorpholino, bevorzugt.If R2 + R3 + N are C1- to C4-dialkylmorpholino, then is Dimethylmorpholino, in particular 2,6-dimethylmorpholino, is preferred.

Wenn R6 einen substituierten Phenylrest bedeutet, so steht der Substituent vorzugsweise in m-Stellung zur Verknüpfungsstelle. Bedeutet R6 einen C1- bis C4-Alkylrest oder enthält R einen solchen Rest, so sind Methyl und Äthyl bevorzugt.If R6 is a substituted phenyl radical, then the substituent is preferably in the m-position to the connection point. If R6 is a C1 to C4 alkyl radical or if R contains such a radical, methyl and ethyl are preferred.

Bevorzugte Salze sind die Hydrohalogenide, Hydrogenmaleinate und Hydrogenfumarate.Preferred salts are the hydrohalides, hydrogen maleate and hydrogen fumarates.

Erfindungsgemässe Verbindungen sind beispielsweise 2,6-Diacetyl-5-methyl-3-(4-cyano-4-phenyl-piperidino)-phenol vom F. 160 - 162 0C; 2-Hydroxy-6-methyl-4-(2,6-dimethyl-N-morpholino)-isophthalsäurediäthylester vom F. 63 - 65 OC; 2-Hydroxy-6-methyl-4-(N-1,2,3,4-tetrahydroisochinolino)-isophthalsäurediäthylester vom F. 121 - 123 OC; 2,6-Diacetyl-5-methyl-3-(4-benzyl-N-piperazino)-phenol vom F. 88 - 90 OC und 2-Hydroxy-6-methyl-4-~T-(3-trifluormethylphenyl)-N-piperazino/-isophthalsäurediäthylester vom F. 109 - 111 °C Das als Ausgangsprodukt des erfindungsgemässen Verfahrens dienende 3,5-Diacetyl-2,6-dimethyl-4H-pyran-4-on (Verbindung der allgemeinen Formel II mit R1 = Methyl) kann man nach der Verfahrensweise von Thomas und Lefevre (Bull. Soz. Chim. Fr., Bd. 50 (2), Seite 193 (1888)) aus Kupferacetylacetonat und Phosgen synthetisieren. Zur Herstellung der Ausgangsverbindungen der allgemeinen Formel II, in denen der Rest R1 = oR5 ist, kann man das Kupfersalz des entsprechenden Acetessigsäureesters mit Phosgen nach der Methode von Conrad und Guthzeit (Ber. Dtsch. Chem. Ges., Bd. 19, Seite 22 (1886); Bd. 20, Seite 152 (1887)) herstellen. Der nach dieser Verfahrensweise hergestellte 2,6-Dimethyl-4H-pyran-4-on-3,5-dicarbonsäurediäthylester hat einen F. 81 OC (Äthanol).Compounds according to the invention are, for example, 2,6-diacetyl-5-methyl-3- (4-cyano-4-phenyl-piperidino) -phenol mp 160-162 ° C; 2-Hydroxy-6-methyl-4- (2,6-dimethyl-N-morpholino) -isophthalic acid diethyl ester from m.p. 63-65 ° C; 2-Hydroxy-6-methyl-4- (N-1,2,3,4-tetrahydroisoquinolino) isophthalic acid diethyl ester from mp 121-123 OC; 2,6-Diacetyl-5-methyl-3- (4-benzyl-N-piperazino) -phenol vom F. 88-90 ° C. and 2-hydroxy-6-methyl-4- ~ T- (3-trifluoromethylphenyl) -N-piperazino / isophthalic acid diethyl ester with a temperature of 109 - 111 ° C As the starting product of the invention Process serving 3,5-diacetyl-2,6-dimethyl-4H-pyran-4-one (compound of the general Formula II with R1 = methyl) can be prepared using the procedure of Thomas and Lefevre (Bull. Soz. Chim. Fr., Vol. 50 (2), page 193 (1888)) from copper acetylacetonate and Synthesize phosgene. For the preparation of the starting compounds of the general Formula II, in which the radical R1 = OR5, you can use the copper salt of the corresponding Acetoacetic acid ester with phosgene according to the method of Conrad and Guthzeit (Ber. German Chem. Ges., Vol. 19, p. 22 (1886); Vol. 20, page 152 (1887)). The 2,6-dimethyl-4H-pyran-4-one-3,5-dicarboxylic acid diethyl ester prepared by this procedure has an F. 81 OC (ethanol).

Geht man zur Durchführung des erfindungsgemässen Verfahrens von 3,5-Diacetyl-2,6-dimethyl-4H-pyran-4-on aus, so beträgt die Reaktionszeit im allgemeinen 0,5 bis 2 Stunden bei einer Temperatur von 50 bis 150 OC, insbesondere etwa 100 °C. Ein Lösungsmittel ist im allgemeinen nicht notwendig.If the process according to the invention is carried out from 3,5-diacetyl-2,6-dimethyl-4H-pyran-4-one off, the reaction time is generally 0.5 to 2 hours at one temperature from 50 to 150.degree. C., in particular about 100.degree. A solvent is generally unnecessary.

Geht man von Ausgangsverbindungen der allgemeinen Formel II aus, in denen R1 = OR5 ist, so arbeitet man vorzugsweise in Gegenwart eines Lösungsmittels, wie äthanol, und erhitzt unter Rückfluss ca. 1 bis 50 Stunden. In manchen Fällen, z.B.If one proceeds from starting compounds of the general formula II, in where R1 = OR5, it is preferably carried out in the presence of a solvent, like ethanol, and heated under reflux for about 1 to 50 hours. In some cases, e.g.

bei Verwendung von 1,2,3,4-Tetrahydroisochinolin oder Dialkylmorpholinen, kann die Umsetzung auch ohne Lösungsmittel in der Schmelze erfolgen, wobei die Umsetzungszeit dann 1 bis 3 Stunden beträgt.when using 1,2,3,4-tetrahydroisoquinoline or dialkylmorpholines, the reaction can also be carried out in the melt without a solvent, the reaction time being then 1 to 3 hours.

Die Säureadditionssalze erhält man durch Umsetzung mit einer Säure in bekannter Weise.The acid addition salts are obtained by reaction with an acid in a known way.

Man erhält durch die erfindungsgemässe Umsetzung von Verbindungen der allgemeinen Formel II, worin R1 Methyl bedeutet mit einem sekundären Amin erfindungsgencsse Verbindungen der allgemeinen Formel Diese kann man nach der Verfahrensweise von Föhlisch (Ber.The inventive reaction of compounds of the general formula II in which R1 denotes methyl with a secondary amine gives compounds of the general formula according to the invention This can be done according to the method of Föhlisch (Ber.

Dtsch. Chem. Ges., Bd. 104, Seite 348 (1971) ) mit einem Dimethylformamiddiacetaly beispielsweise dem Dimethylacetal oder Diisopropylacetal, zu Verbindungen der allgemeinen Formel umsetzen. So erhält man beispielsweise die Verbindung l-Acetyl-3-(3-dimethylamino-acryloyl)-2-hydroxy-6-methyl-4-(piperidin-1-yl)-benzol vom F. 138 OC, Setzt man dieses Enaminoketon (Verbindung der allgemeinen Formel IV) mit Säure,z.B. mit verdünnter Schwefelsäure, vorzugsweise in der Wärme, um, so erhält man Chromonverbindungen der allgemeinen Formel Die Cyclisierung erfolgt nach der Vorschrift von Föhlisch (Ber. Dtsch. Chem. Ges., Bd. 104, Seite 348 (1971) ). Eine so hergestellte Verbindung ist beispielsweise 8-Acetyl-7-methyl-5-(piperidin-1-yl) -4H-benzo/b~7pyran-4-on vom F. 141 bis 142 °C.German Chem. Ges., Vol. 104, page 348 (1971)) with a dimethylformamide diacetaly, for example dimethyl acetal or diisopropyl acetal, to give compounds of the general formula realize. For example, the compound l-acetyl-3- (3-dimethylamino-acryloyl) -2-hydroxy-6-methyl-4- (piperidin-1-yl) benzene with a melting point of 138 OC is obtained. Compound of the general formula IV) with acid, for example with dilute sulfuric acid, preferably in the heat, to obtain chromone compounds of the general formula The cyclization is carried out according to the instructions of Föhlisch (Ber. Dtsch. Chem. Ges., Vol. 104, page 348 (1971)). A compound prepared in this way is, for example, 8-acetyl-7-methyl-5- (piperidin-1-yl) -4H-benzo / b ~ 7pyran-4-one with a melting point of 141 to 142 ° C.

Die Chromonverbindungen (V) lassen sich mit einem Hydrazin der allgemeinen Formel 8 H2N-NHR8 , VI worin R8 Wasserstoff, Methyl, Athyl oder Phenyl bedeutet, zu Benzolverbindungen der allgemeinen Formel umsetzen. Die Umsetzung erfolgt vorzugsweise unter Rückfluss in einem Lösungsmittel, insbesondere Äthanol. Die Verfahrensdauer beträgt mehrere Stunden. Man kann so z.B.The chromone compounds (V) can be converted to benzene compounds of the general formula with a hydrazine of the general formula 8H2N-NHR8, VI in which R8 is hydrogen, methyl, ethyl or phenyl realize. The reaction is preferably carried out under reflux in a solvent, in particular ethanol. The procedure takes several hours. You can for example

l-Acetyl-2-hydroxy-6-methyl-3-(1-phenyl-pyrazol-5-yl)-4-(piperidin-1-yl)-benzol vom F. 142 OC, l-Acetyl-2-hydroxy-6-methyl-3-(1-methyl-pyrazol-5-yl)-4-(piperidin-1-yl)-benzol vom F. 162 CC oder l-Acetyl-2-hydroxy-6-methyl-3-(pyrazol-5-yl)-4-(piperidin-1-yl)-benzol vom F. 195 OC synthetisieren.1-Acetyl-2-hydroxy-6-methyl-3- (1-phenyl-pyrazol-5-yl) -4- (piperidin-1-yl) -benzene vom F. 142 OC, 1-acetyl-2-hydroxy-6-methyl-3- (1-methyl-pyrazol-5-yl) -4- (piperidin-1-yl) -benzene vom F. 162 CC or 1-acetyl-2-hydroxy-6-methyl-3- (pyrazol-5-yl) -4- (piperidin-1-yl) -benzene synthesize from F. 195 OC.

Die Benzolverbindungen (VII) kann man aber auch herstellen, indem man eine Enaminoketonverbindung (IV) unmittelbar mit einer Hydrazinverbindung (VI) in einem Lösungsmittel, vorzugsweise Äthanol, in Gegenwart einer Säure, z.B. Eisessig, umsetzt. Die Umsetzung erfolgt insbesondere in der Wärme, z.B. unter Rückfluss.The benzene compounds (VII) can also be prepared by one enaminoketone compound (IV) directly with a hydrazine compound (VI) in a solvent, preferably ethanol, in the presence of an acid, e.g. glacial acetic acid, implements. The conversion takes place in particular in the heat, e.g. under reflux.

Die erfindungsgemässen Verbindungen der Formel I haben vor allem Wirkungen auf Herz und Kreislauf. Auch die Verbindungen der allgemeinen Formel VII haben arzneiliche, vor allem Herz- und Kreislaufwirkungen.The compounds of the formula I according to the invention have above all effects on the heart and circulation. The compounds of the general formula VII also have medicinal, especially cardiovascular effects.

Die erfindungsgemässen Verbindungen können zu üblichen flüssigen oder festen Arzneimittelzubereitungen verarbeitet werden, beispielsweise zu Dragees, Tabletten, Suppositorien und Lösungen, auch für die Injektion. Hierzu werden übliche Träger- und Verdünnungsmittel und übliche Verfahrensweisen verwendet.The compounds according to the invention can be added to conventional liquid or solid pharmaceutical preparations are processed, for example into coated tablets, Tablets, suppositories and solutions, also for injection. For this purpose, the usual Carriers and diluents and conventional procedures used.

Die orale Einzeldosis beträgt 1 bis 10 mg/kg, die orale Tagesdosis beträgt 3 bis 30 mg/kg. Die parenterale Einzeldosis beträgt 0,1 bis 2 mg/kg, die parenterale Tagesdosis beträgt ,3 bis 6 mg/kg.The oral single dose is 1 to 10 mg / kg, the oral daily dose is 3 to 30 mg / kg. The single parenteral dose is 0.1 to 2 mg / kg, the parenteral daily dose is 3 to 6 mg / kg.

Beispiel 1 1 ,3-Diacetyl-2-hydroxy-4-methyl-6-(piperidin-1-yl)-benzol 2 g (0,01 Mol) 355-Diacetyl-2,6-dimethyl-4H-pyran-4-on werden ohne Lösungsmittel mit 950 mg (0,011 Mol) Piperidin 1 1/2 Stunden bei 100 OC gehalten. Nach Zugabe von wenig Äthanol kristallisiert die gesuchte Verbindung in gelblichen Kristallen; F. 95-96 OC; Ausb. 2,2 g (84 % d. Th.).Example 1 1,3-Diacetyl-2-hydroxy-4-methyl-6- (piperidin-1-yl) -benzene 2 g (0.01 mol) of 355-diacetyl-2,6-dimethyl-4H-pyran-4-one become without a solvent with 950 mg (0.011 mol) of piperidine held at 100 ° C. for 1 1/2 hours. After adding from a little ethanol the sought compound crystallizes in yellowish crystals; F. 95-96 OC; Yield 2.2 g (84% of theory).

Beispiel 2 1,3-Diacetyl-2-hydroxy-4-methyl-6-(pyrrolidin-1-yl)-benzol 2 g (0,01 Mol) 3,5-Diacetyl-2,6-dimethyl-4H-pyran-4-on werden mit 690 mg (0,011 Mol) Pyrrolidin nach der Verfahrensweise des Beispiels 1 behandelt.Example 2 1,3-Diacetyl-2-hydroxy-4-methyl-6- (pyrrolidin-1-yl) -benzene 2 g (0.01 mol) of 3,5-diacetyl-2,6-dimethyl-4H-pyran-4-one are mixed with 690 mg (0.011 Mol) pyrrolidine treated according to the procedure of Example 1.

Gelbliche Kristalle aus Äthanol, F. 129 OC; Ausb. 1,8 g (71 % d. Th.).Yellowish crystals from ethanol, m.p. 129 OC; Yield 1.8 g (71% of theory).

Beispiel 3 1 2-hydroxy-4-methyl-6-(morpholin-4-y)-be 2 g (0,01 Mol) 3,5-Diacetyl-2,6-dimethyl-4H'-pyran-4-on werden mit 900 mg Morpholin nach der Verfahrensweise des Beispiels 1 behandelt.Example 3 1 2-hydroxy-4-methyl-6- (morpholin-4-y) -be 2 g (0.01 mol) 3,5-Diacetyl-2,6-dimethyl-4H'-pyran-4-one are mixed with 900 mg of morpholine according to the procedure of Example 1 treated.

Gelbliche Kristalle aus Athanol; F. 78 OC; Aush. 1,8 g (69 % d. Th.).Yellowish crystals of ethanol; M.p. 78 OC; Excluding 1.8 g (69% of theory).

Beispiel 4 1,5-Diacetyl-2-methyloxy-4-methyl-6-tpiperidin-1-yl)-benzol 0,5 g (0,002 Mol) 1,3-Diacetyl-2-hydroxy-4-methyl-6-(piperidinl-yl)-benzol werden nach der Vorschrift von Kostanecki (Ber. Dtsch. Chem. Ges., Bd. 35, Seite 1669 (1902)) mit Dimethylsulfat und KOH methyliert.Example 4 1,5-Diacetyl-2-methyloxy-4-methyl-6-tpiperidin-1-yl) -benzene 0.5 g (0.002 mol) of 1,3-diacetyl-2-hydroxy-4-methyl-6- (piperidinl-yl) -benzene according to the instructions of Kostanecki (Ber. Dtsch. Chem. Ges., Vol. 35, page 1669 (1902)) methylated with dimethyl sulfate and KOH.

Farblose Kristalle aus Äthanol; F. 75 OC; Ausb. 480 mg (93 % d. Th.).Colorless crystals of ethanol; M.p. 75 OC; Yield 480 mg (93% of theory).

Beispiel 5 2-Hydroxy-4-methyl-6-(piperidin-1-yl)-benzol-1,3-dicarbonsäure-diäthylester 2 g (0,0074 Mol) 2,6-Dimethyl-4H-pyran-4-on-3,5-dicarbonsäurediäthylester werden mit 1,9 g t0,0223 Mol) Piperidin in 5 ml Äthanol 1 Stunde rückfliessend erhitzt. Nach dem Abkühlen farblose Kristalle aus Athanol; F. 56 OC; Ausb. 1>4 g (58 % d. Th.).Example 5 2-Hydroxy-4-methyl-6- (piperidin-1-yl) -benzene-1,3-dicarboxylic acid diethyl ester 2 g (0.0074 mol) of 2,6-dimethyl-4H-pyran-4-one-3,5-dicarboxylic acid diethyl ester refluxed with 1.9 g t0.0223 mol) of piperidine in 5 ml of ethanol for 1 hour. After cooling, colorless crystals of ethanol; F. 56 OC; Yield 1> 4 g (58% d. Th.).

Ende der BeschreibungEnd of description

Claims (3)

Patentansprüche 1.2-Hydroxy-4-methyl-benzolverbindungen der allgemeinen Formel worin bedeuten R1 beide Methyl oder beide OR5 mit R5 gleich C1- bis C4-Alkyl R2 und R3 C1- bis C4-Alkyl oder R2 + R3 + N Pyrrolidino Piperidino 4-Cyano-4-phenyl-piperidino Azepino N-Methyl-1,4-diazepino Morpholino C1- bis C4-Dialkyl-morpholino 1,2,3,4-Tetrahydroisochinolino einen Rest der allgemeinen Formel 6 wobei R6 bedeutet C1- bis C4-Alkyl ß -Hydroxyäthy 1 Phenyl C1- bis C4-Alkylphenyl C1- bis C4-Alkoxyphenyl Halogenphenyl Trifluormethylphenyl R4 H Methyl ethyl und ihre Säureadditionssalze.Claims 1,2-hydroxy-4-methyl-benzene compounds of the general formula where R1 is both methyl or both OR5 with R5 being C1- to C4-alkyl R2 and R3 C1- to C4-alkyl or R2 + R3 + N pyrrolidino piperidino 4-cyano-4-phenyl-piperidino azepino N-methyl-1, 4-diazepino morpholino C1- to C4-dialkyl-morpholino 1,2,3,4-tetrahydroisoquinolino a radical of the general formula 6 where R6 is C1- to C4-alkyl ß-hydroxyethy 1 phenyl C1- to C4-alkylphenyl C1- to C4-alkoxyphenyl halophenyl trifluoromethylphenyl R4 H methyl ethyl and its acid addition salts. 2. Verfahren zur Herstellung der Verbindungen gemäss Anspruch 1, dadurch gekennzeichnet, dass man eine 2,6-Dimethyl-4H-pyran-4-on-Verbindung der allgemeinen Formel mit einem sekundären Amin der allgemeinen Formel oder mit Pyrrolidin, Piperidin, 4-Cyano-4-phenyl-piperidin Azepin, N-Methyl-1,4-diazepin, Morpholin, C1 bis C4-Dialkylmorpholin, 1,2,3,4-Tetrahydroisochinolin oder mit einer Piperazinverbindung der allgemeinen Formel umsetzt und gegebenenfalls die erhaltene Verbindung in an sich bekannter Weise an der Hydroxylgruppe methyliert oder äthyliert und/oder in ein Säureadditionssalz überführt.2. Process for the preparation of the compounds according to claim 1, characterized in that a 2,6-dimethyl-4H-pyran-4-one compound of the general formula is used with a secondary amine of the general formula or with pyrrolidine, piperidine, 4-cyano-4-phenyl-piperidine, azepine, N-methyl-1,4-diazepine, morpholine, C1 to C4-dialkylmorpholine, 1,2,3,4-tetrahydroisoquinoline or with a piperazine compound in general formula reacted and, if appropriate, the compound obtained is methylated or ethylated on the hydroxyl group in a manner known per se and / or converted into an acid addition salt. 3. Verwendung der Verbindungen des Anspruches 1 bei der Bekämpfung von Kreislauf- und Herzbeschwerden.3. Use of the compounds of claim 1 in combating of circulatory and heart problems.
DE19792922488 1979-06-01 1979-06-01 2-Hydroxy-4-amino-6-methyl-isophthalic acid - and 2,6-di:acetyl-3-hydroxy-5-methylphenol derivs. with cardiovascular activity Withdrawn DE2922488A1 (en)

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US8404681B2 (en) 2003-03-24 2013-03-26 Luitpold Pharmaceuticals, Inc. Xanthones, thioxanthones and acridinones as DNA-PK inhibitors

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Publication number Priority date Publication date Assignee Title
WO2002020500A2 (en) * 2000-09-01 2002-03-14 Icos Corporation Materials and methods to potentiate cancer treatment
WO2002020500A3 (en) * 2000-09-01 2003-07-31 Icos Corp Materials and methods to potentiate cancer treatment
US7179912B2 (en) 2000-09-01 2007-02-20 Icos Corporation Materials and methods to potentiate cancer treatment
US8242115B2 (en) 2000-09-01 2012-08-14 Luitpold Pharmaceuticals, Inc. Materials and methods to potentiate cancer treatment
US8404681B2 (en) 2003-03-24 2013-03-26 Luitpold Pharmaceuticals, Inc. Xanthones, thioxanthones and acridinones as DNA-PK inhibitors

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