DE3444135A1 - Selenoxides, process for their preparation and pharmaceutical preparations containing them - Google Patents
Selenoxides, process for their preparation and pharmaceutical preparations containing themInfo
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- DE3444135A1 DE3444135A1 DE19843444135 DE3444135A DE3444135A1 DE 3444135 A1 DE3444135 A1 DE 3444135A1 DE 19843444135 DE19843444135 DE 19843444135 DE 3444135 A DE3444135 A DE 3444135A DE 3444135 A1 DE3444135 A1 DE 3444135A1
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- benzisoselenazol
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D293/00—Heterocyclic compounds containing rings having nitrogen and selenium or nitrogen and tellurium, with or without oxygen or sulfur atoms, as the ring hetero atoms
- C07D293/10—Heterocyclic compounds containing rings having nitrogen and selenium or nitrogen and tellurium, with or without oxygen or sulfur atoms, as the ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D293/12—Selenazoles; Hydrogenated selenazoles
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Abstract
Description
Titel: Selenoxide, Verfahren zu ihrer Her-Title: Selenium Oxides, Process for Their Manufacture
stellung und diese enthaltende pharmazeutische Präparate. position and pharmaceutical preparations containing them.
Beschreibung Die Erfindung betrifft neue Selenoxide von Benzisoselenazolonen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zubereitungen und ihre Verwendung bei der Therapie von rheumatischen Erkrankunyen.Description The invention relates to new selenium oxides of benzisoselenazolones, Process for their preparation and pharmaceutical compositions containing these compounds Preparations and their use in the therapy of rheumatic diseases.
Benzisoselenazolone mit antiarteriosklerotischen und entzündungshemmenden Eigenschaften sind bereits mehrfach beschrieben worden, so z.B. in DE-OS 30 27 073r DE-OS 3U 27 074, DE-OS 30 27 076.Benzisoselenazolone with anti-arteriosclerotic and anti-inflammatory Properties have already been described several times, e.g. in DE-OS 30 27 073r DE-OS 3U 27 074, DE-OS 30 27 076.
Es wurde nun gefunden, daß Benzisoselenazolon-selenoxide der allyemeinen Formel I worin R1, R2 gleich oder verschieden sind und unabhängig voneinander Wasserstoff, Fluor, Chlor, Brom, C14-Alkyl, C14-Alkoxy, Hydroxy, Trifluormethyl, Nitro oder zusammen Methylendioxy bedeuten und R3, R4 gleich oder verschieden sind und unabhängig voneinander für Wasserstoff, Fluor, Chlor, Brom, C1-4-Alkyl, C14-Alkoxy, Hydroxy, Trifluormethyl, Nitro, Di-(C1,4-Alkyl)-aminor Cyan, -COOR5, CHR6-CooR5 oder zusammen für Methylendioxy stehen, wobei R5 Wasserstoff, ein Alkali in oder C14-Alkyl und R6 Wasserstoff, Methyl oder Ethyl darstellen und n Null oder eine ganze Zahl von 1 bis 4 ist, wertvolle pharmakologische Eigenschaften aufweisen.It has now been found that benzisoselenazolone selenium oxides of the general formula I in which R1, R2 are identical or different and are independently hydrogen, fluorine, chlorine, bromine, C14-alkyl, C14-alkoxy, hydroxy, trifluoromethyl, nitro or together are methylenedioxy and R3, R4 are identical or different and are independently hydrogen, Fluorine, chlorine, bromine, C1-4-alkyl, C14-alkoxy, hydroxy, trifluoromethyl, nitro, di- (C1,4-alkyl) -amino cyano, -COOR5, CHR6-CooR5 or together represent methylenedioxy, where R5 is hydrogen , an alkali in or C14-alkyl and R6 represent hydrogen, methyl or ethyl and n is zero or an integer from 1 to 4, have valuable pharmacological properties.
Bevorzugt sind dabei Benzisoselenazolon-selenoxide der allyemeinen Formel I, worin n = 0 und entweder R1 und R2 oder R1 und R3 stets Wasserstoff sind und die anderen Substituenten (R3 und R4 bzw. R2 und R4) Fluor, Chlor, Brom, Hydroxy, Methoxy, Methyl, Trifluormethyl oder Nitro sind.Benzisoselenazolone-selenoxides of the allyeminen are preferred Formula I, in which n = 0 and either R1 and R2 or R1 and R3 are always hydrogen and the other substituents (R3 and R4 or R2 and R4) fluorine, chlorine, bromine, hydroxy, Are methoxy, methyl, trifluoromethyl or nitro.
Eine andere bevorzuyte Gruppe der Benzisoselenazolonselenoxide der Formel I sind diejenigen, worin n Null oder eine ganze Zahl von 1 bis 4 ist, R1, R2 und R3 Wasserstoff sind und R4 -CN, -CooR5 oder -CHR6-CooR5 sind, wobei R5 Wasserstoff, Natrium, Methyl oder Ethyl und R6 Wasserserstoff, Methyl oder Ethyl darstellen.Another preferred group of benzisoselenazolone selenoxides Formula I are those in which n is zero or an integer from 1 to 4, R1, R2 and R3 are hydrogen and R4 are -CN, -CooR5 or -CHR6-CooR5, where R5 is hydrogen, Sodium, methyl or ethyl and R6 represent hydrogen, methyl or ethyl.
Bevorzugte Reste am Stickstoffatom der Benzisoselenazolonselenoxide sind z.B.: bei n = 0: 4-Fluorphenyl, 4-Chlorphenyl, 4-Hydroxyphenyl, 4-Methoxyphenyl, 4-Methylphenyl, 4-Trifluormethylphenyl, 4-Nitrophenyl, 4-Dimethylaminophenyl, 3-Brom-4-hydroxyphenyl, 3,4-Methylendioxyphenyl, 2-Hydroxyphenyl, 3-Hydroxyphenyl, 2-Fluorphenyl und 3-Methoxyphenyl, bei n / 0: 2-(4-Fluorphenyl)-ethyl, 4-Phenylbutyl, 3-Phenylpropyl, 2-Phenylethyl und 4-(4-Chlorphenyl)-butyl, bei n = 0 und R3 = H: 4-Carboxyphenyl, 4-Ethoxycarbonylphenyl, 4-Carboxymethylphenyl, 4-Ethoxycarbonylmethylphenyl, 4-(l-Ethoxycarbonyl-ethyl)phenyl, 4-Cyanphenyl.Preferred residues on the nitrogen atom of the benzisoselenazolone selenoxides are e.g .: when n = 0: 4-fluorophenyl, 4-chlorophenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-nitrophenyl, 4-dimethylaminophenyl, 3-bromo-4-hydroxyphenyl, 3,4-methylenedioxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-fluorophenyl and 3-methoxyphenyl, at n / 0: 2- (4-fluorophenyl) -ethyl, 4-phenylbutyl, 3-phenylpropyl, 2-phenylethyl and 4- (4-chlorophenyl) -butyl, when n = 0 and R3 = H: 4-carboxyphenyl, 4-ethoxycarbonylphenyl, 4-carboxymethylphenyl, 4-ethoxycarbonylmethylphenyl, 4- (l-ethoxycarbonyl-ethyl) phenyl, 4-cyanophenyl.
Erfindungsgemäße Verbindungen sind beispielsweise: 2-Phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-Methylphenyl)-1,2-benzisoselenazo1-3(2H)-on-Se-oxid 2-(4-Fluorphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-Chlorphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-MethOxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-Nitrophenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-EthOxycarbonylphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-E4-(1-EthOxycarbonylethyl)-phenyl7-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(2-Fluorphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-S4-(EthOxyzarbonylmethyl)-phenyQ7-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3,4-Methylendioxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3-MethOxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-Cyanphenyl)-l,2-benzisoselenazol-3<2H)-on-Se-oxid 2-(4-Dimethylaminophenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-Hydroxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3-Hydroxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(2-Hydroxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 6-Fluor-2-phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid 6-Methyl-2-phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxìd 6-chlor-2-phenyl-lt2-benzisoselenazol-3(2H)-on-se-oxid 6-MethOxy-2-phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid 5-Nitro-2-piienyl-l,2-benzisoselenazol-3( 2H)-on-Se-oxid 5-Chlor-2-phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid 7-Methoxy-2-phenyl-l,2-benzisoselenazol-3< 211)-on-Se-oxid 6,7-Methylendioxy-2-phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid 6-Hydroxy-2-phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid 5-Hydroxy-2-phenyl-l,2-benzisoselenazol-3< 2H)-on-Se-oxid 2-(4-Trifluormethylphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-Benzyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-Phenylbutyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3-Brom-4-hydroxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-chlorphenyl)-7-methoxy-lt2-benzisoselenazol-3(2H)-on Se-oxid 7-MethOxy-2-(4-methylphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 7-MethOxy-2-(4-nitrophenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3-Fluorphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxia 2-(3-Chlorphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 7-MethOxy-2-(3-methylphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 7-MethOxy-2-(3-methoxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 7-MethOxy-2-(3-nitrophenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3,4-Dichlorphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3,4-Difluorphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3,4-Dimethylphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3-Fluor-4-methylphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3-Chlor-4-methoxyphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3,4-Dimethoxyphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-Fluor-3-methylphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(4-Chlor-3-fluorphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 2-(3-Chlor-4-fluorphenyl)-7-methoxy-1,2-benzisoselenazol-3(2H)-on-Se-oxid 7-MethOxy-2-(3-methoxy-4-methylphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 7-MethOxy-2-(4-methoxy-3-methylphenyl)-l,Z-benzisoselenazol-3(2H)-on-Se-oxid 7-Methoxy-2-(2-methoxy-4-nitrophenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid 7-MethOxy-2-(4-methoxy-2-nitrophenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid Die erfindungsgemäßen Selenoxide der Formel I zeigen im CVF (Cobra venom factor) -induzierten Pfotenödemmodell (S. Leyck, u.a., Agents and Actions, Vol. 13, 5/6 (1983)) gegenüber den nicht oxidierten Verbindungen überlegene entzündunyshemmende Eigenschaften Darüber hinaus werden nach Verabreichung der Selenoxide höhere Plasmaspiegel erreicht als mit den nicht oxidierten Verbindungen.Examples of compounds according to the invention are: 2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-methylphenyl) -1,2-benzisoselenazo1-3 (2H) -one-Se-oxide 2- (4-fluorophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-Chlorophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-MethOxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-Nitrophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-Ethoxycarbonylphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2-E4- (1-Ethoxycarbonylethyl) -phenyl7-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (2-fluorophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se -oxide 2-S4- (ethoxyzarbonylmethyl) -phenyQ7-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3,4-methylenedioxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se -oxide 2- (3-Methoxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-Cyanophenyl) -1,2-benzisoselenazol-3 <2H) -one-Se-oxide 2- (4-Dimethylaminophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-Hydroxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3-Hydroxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (2-Hydroxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 6-fluoro-2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 6-methyl-2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide. 6-chloro-2-phenyl-lt2-benzisoselenazol-3 (2H) -one-se-oxide 6-methoxy-2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 5-nitro-2-piienyl-1,2-benzisoselenazol-3 ( 2H) -one-Se-oxide 5-chloro-2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 7-methoxy-2-phenyl-1,2-benzisoselenazol-3 < 211) -one-Se-oxide 6,7-methylenedioxy-2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 6-Hydroxy-2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 5-Hydroxy-2-phenyl-1,2-benzisoselenazol-3 < 2H) -one-Se-oxide 2- (4-Trifluoromethylphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2-Benzyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-Phenylbutyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3-Bromo-4-hydroxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-chlorophenyl) -7-methoxy-lt2-benzisoselenazol-3 (2H) -one Se oxide 7-methoxy-2- (4-methylphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 7-methoxy-2- (4-nitrophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3-fluorophenyl) -7-methoxy-1,2-benzisoselenazol-3 (2H) -one-Se-oxia 2- (3-chlorophenyl) -7-methoxy-1,2-benzisoselenazol-3 (2H) -on-Se-oxide 7-MethOxy-2- (3-methylphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 7-MethOxy-2- (3-methoxyphenyl) -1,2-benzisoselenazol-3 (2H) -on-Se-oxide 7-methoxy-2- (3-nitrophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3,4-dichlorophenyl) -7-methoxy-1,2-benzisoselenazol-3 ( 2H) -one-Se-oxide 2- (3,4-Difluorophenyl) -7-methoxy-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3,4-Dimethylphenyl) -7-methoxy-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3-fluoro-4-methylphenyl) -7-methoxy-1,2- benzisoselenazol-3 (2H) -one-Se-oxide 2- (3-chloro-4-methoxyphenyl) -7-methoxy-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3,4-dimethoxyphenyl) -7-methoxy-1,2- benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-fluoro-3-methylphenyl) -7-methoxy-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (4-chloro-3-fluorophenyl) -7-methoxy-1, 2-benzisoselenazol-3 (2H) -one-Se-oxide 2- (3-chloro-4-fluorophenyl) -7-methoxy-1,2-benzisoselenazol-3 (2H) -one-Se-oxide 7-methoxy-2- (3-methoxy-4-methylphenyl) -1, 2-benzisoselenazol-3 (2H) -one-Se-oxide 7-methoxy-2- (4-methoxy-3-methylphenyl) -1, Z-benzisoselenazol-3 (2H) -one-Se-oxide 7-methoxy-2- (2-methoxy-4-nitrophenyl) -1, 2-benzisoselenazol-3 (2H) -one-Se-oxide 7-Methoxy-2- (4-methoxy-2-nitrophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide The Selenium oxides of the formula I according to the invention show in the CVF (Cobra venom factor) -induced Paw edema model (S. Leyck, et al., Agents and Actions, Vol. 13, 5/6 (1983)) superior anti-inflammatory properties to non-oxidized compounds In addition, higher plasma levels are reached after administration of the selenium oxides than with the non-oxidized compounds.
Die Herstellung der erfindungsgemäßen Verbindungen erfolgt nach an sich bekannten Verfahren durch Oxydation von Benzisoselenazolonen der Formel II, in der R1, R2, R3, R4 und n die in Formel I angegebenen Bedeutungen haben, mit Wasserstoffperoxid. The compounds according to the invention are prepared by processes known per se by oxidation of benzisoselenazolones of the formula II, in which R1, R2, R3, R4 and n have the meanings given in formula I, with hydrogen peroxide.
Die Oxydation wird mit dem in einem chlorierten Kohlenwasserstoff wie Dichlormethan, Chloroform, Dichlorethan suspendierten 1,2-Benzisoselenazolon bei Temperaturen von -10" bis +40"C, vorzugsweise 0" bis +20"C in 2 bis 4 Stunden durch Zugabe einer annähernd äquimolaren Menge H202 durchyeführt.The oxidation is carried out with that in a chlorinated hydrocarbon such as dichloromethane, chloroform, dichloroethane suspended 1,2-benzisoselenazolone at temperatures from -10 "to +40" C, preferably 0 "to +20" C in 2 to 4 hours carried out by adding an approximately equimolar amount of H 2 O 2.
Die Darstellung der dafür benötigten Benzisoselenazolone ist in DE-OS 30 27 073, DE-OS 30 27 074 und DE-OS 30 27 075 beschrieben.The representation of the benzisoselenazolones required for this is in DE-OS 30 27 073, DE-OS 30 27 074 and DE-OS 30 27 075 described.
Die vorliegende Erfindung betrifft ebenfalls pharmazeutische Präparate, welche Verbindungen der Formel I enthalten. Bei den erfindungsgemäßen pharmazeutischen Präparaten handelt es sich um solche zur enteralen wie oralen oder rektalen sowie parenteralen Verabreichung, welche die pharmazeutischen Wirkstoffe allein oder zusammen mit einem üblichen, pharmazeutisch anwendbaren Trägermaterial enthalten. Vorteilhafterweise liegt die pharmazeutische Zubereitung des Wirkstoffes in Form von Einzeldosen vor, die auf die gewünschte Verabreichung abgestimmt sind, wie z.B.The present invention also relates to pharmaceutical preparations, which compounds of formula I contain. In the pharmaceutical according to the invention Preparations are those for enteral such as oral or rectal as well parenteral administration containing the active pharmaceutical ingredients alone or together with a conventional, pharmaceutically applicable carrier material. Advantageously if the pharmaceutical preparation of the active ingredient is available in the form of single doses, tailored to the desired administration, e.g.
Tabletten, Dragees, Kapseln, Suppositorien, Granulate, Lösungen, Emulsionen oder Suspensionen. Die Dosierung der Substanzen liegt überlicherweise zwischen 10 und 1000 mg pro Tay, vorzugsweise zwischen 30 und 300 mg pro Tag, und kann in einer Dosis oder mehreren Teildosen, vorzugsweise in zwei bis drei Teildosen pro Tag, verabreicht werden.Tablets, coated tablets, capsules, suppositories, granulates, solutions, emulsions or suspensions. The dosage of the Substances usually lies between 10 and 1000 mg per day, preferably between 30 and 300 mg per day, and can be in one dose or in several divided doses, preferably in two to three divided doses per day.
Die Herstellung der erfindungsgemäßen Verbindungen wird durch die folgenden Beispiele erläutert.The preparation of the compounds according to the invention is carried out by the following examples.
Die anyegebenen Schmelzpunkte wurden mit einem Büchi 510-Schmelzpunktbestimmungsapparat gemessen und sind mit "C anyegeben und nicht korrigiert.The given melting points were measured with a Büchi 510 melting point apparatus measured and given with "C any" and not corrected.
Beispiel 1 2-(4-Fluorphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Example 1 2- (4-Fluorophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide.
Zu einer Suspension von 1 9 (3,4 mmol) 2-(4-Fluorphenyl)-1,2-benzisoselenazol-3(2H)-on in 50 ml Dichlormethan werden unter Eiskühlung 0,43 ml (3,7 mmol) 30-%iges Wasserstoffperoxid zugegeben. Die Mischung wird weitere 2 Stunden bei etwa 0° und weitere 2 Stunden bei Raumtemperatur yerührt. Der weiße Niederschlag wird abgesaugt und mit Dichlormethan gewaschen.To a suspension of 19 (3.4 mmol) 2- (4-fluorophenyl) -1,2-benzisoselenazol-3 (2H) -one 0.43 ml (3.7 mmol) of 30% strength hydrogen peroxide are added to 50 ml of dichloromethane while cooling with ice admitted. The mixture is left for an additional 2 hours at about 0 ° and an additional 2 hours stirred at room temperature. The white precipitate is filtered off and washed with dichloromethane washed.
Ausbeute: 0,98 g (93,3 % d.Th.), Fp. 190-193"C (Zers.) Beispiel 2 2-(3,4-Metylendioxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 0.98 g (93.3% of theory), melting point 190-193 "C (decomp.) Example 2 2- (3,4-Metylenedioxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide.
Analog Beispiel 1 aus 1,25 g 2-(3,4-Methylendioxyphenyl)-1,2-benzisoselenazol-3(2H)-on und 0,5 ml 30-%igem Wasserstoffperoxid in 100 ml Dichlormethan.Analogously to Example 1 from 1.25 g of 2- (3,4-methylenedioxyphenyl) -1,2-benzisoselenazol-3 (2H) -one and 0.5 ml of 30% hydrogen peroxide in 100 ml of dichloromethane.
Ausbeute: 1,28 g (97,7 % d.Th.), Fp. 150"C (Zers.) Beispiel 3 2-(4-Nitrophenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 1.28 g (97.7% of theory), melting point 150 "C (decomp.) example 3 2- (4-nitrophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide.
Analoy Beispiel 1 aus 1 g 2-(4-Nitrophenyl)-1,2-benzisoselenazol-3(2H)-on und 0,39 ml 30-%igem Wasserstoffperoxid in 100 ml Dichlormethan.Analoy example 1 from 1 g of 2- (4-nitrophenyl) -1,2-benzisoselenazol-3 (2H) -one and 0.39 ml of 30% hydrogen peroxide in 100 ml of dichloromethane.
Ausbeute: 1 g (95 % d.Th.), Fp. 265°C (Zers.) Beispiel 4 2-(4-Methylphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 1 g (95% of theory), melting point 265 ° C. (decomp.) Example 4 2- (4-Methylphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide.
Analog Beispiel 1 aus 1 y 2-(4-Methylphenyl)-1,2-benzisoselenazol-3(2H)-on und 0,43 ml 30-%igem Wasserstoffperoxid in 40 ml Dichlormethan.Analogously to example 1 from 1 y 2- (4-methylphenyl) -1,2-benzisoselenazol-3 (2H) -one and 0.43 ml of 30% hydrogen peroxide in 40 ml of dichloromethane.
Ausbeute: 0,76 g (73,3 96 d.Th.), Fp. 130°C (Zers.) Beispiel 5 2-(4-Cyanphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 0.76 g (73.3 96 of theory), melting point 130 ° C. (decomp.) Example 5 2- (4-Cyanophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se -oxide.
Analog Beispiel 1 aus 0,4 y 2-(4-Cyanphenyl)-1,2-benzisoselenazol-3(2H)-on und 0,17 ml 30-%igem Wasserstoffperoxid in 70 ml Dichlormethan.Analogously to example 1 from 0.4 y 2- (4-cyanophenyl) -1,2-benzisoselenazol-3 (2H) -one and 0.17 ml of 30% hydrogen peroxide in 70 ml of dichloromethane.
Ausbeute: 0,41 g (97 % d.Th.), Fp. 228-229°C (Zers.) Beispiel 6 2-f4- < 1- Ethoxycarbonyl-e thyl ) phenyl/M1 2-benz isoselenazol-3(2H)-on-Se-oxid.Yield: 0.41 g (97% of theory), melting point 228-229 ° C. (decomp.) Example 6 2-f4- <1- ethoxycarbonyl-ethyl) phenyl / M1 2-benz isoselenazol-3 (2H) -one-Se-oxide.
Analoy Beispiel 1 aus 1,2 g 2-fi4-(1-Ethoxycarbonyl-ethyl)-phenyl]-1,2-benzisoselenazol-3(2H)-on und 0,4 ml 30-%igem Wasserstoffperoxid in 30 ml Dichlormethan.Analoy example 1 from 1.2 g of 2- (1-ethoxycarbonyl-ethyl) -phenyl] -1,2-benzisoselenazol-3 (2H) -one and 0.4 ml of 30% hydrogen peroxide in 30 ml of dichloromethane.
Ausbeute: 0,75 g (60 90 d.Th.), Fp. 95-98°C Beispiel 7 2-Benzyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 0.75 g (60-90 of theory), melting point 95-98 ° C example 7 2-Benzyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide.
Analog Beispiel 1 aus 2,88 g (10 mmol) 2-Benzyl-1,2-benzisoselenazol-3(2H)-on und 0,5 ml 30+Eigem Wasserstoffperoxid in 50 ml Dichlormethan.Analogously to Example 1 from 2.88 g (10 mmol) of 2-benzyl-1,2-benzisoselenazol-3 (2H) -one and 0.5 ml of 30+ own hydrogen peroxide in 50 ml of dichloromethane.
Ausbeute: 2,8 g (92 % d.Th.), Fp. 130-132"C Beispiel 8 2-(4-MethOxyphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 2.8 g (92% of theory), melting point 130-132 "C Example 8 2- (4-Methoxyphenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide.
Analog Beispiel 1 aus 3,04 g (10 mmol) 2-(4-Methoxyphenyl)-1,2-benzisoselenazol-3(2H)-on und 0,5 ml 30-%igem Wasserstoffperoxid in 50 ml Dichlormethan.Analogously to Example 1 from 3.04 g (10 mmol) 2- (4-methoxyphenyl) -1,2-benzisoselenazol-3 (2H) -one and 0.5 ml of 30% hydrogen peroxide in 50 ml of dichloromethane.
Ausbeute: 2,9 g (90,6 % d.Th.), Fp. 213-216"C Beispiel 9 2-(3-Fluorphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 2.9 g (90.6% of theory), melting point 213-216 "C Example 9 2- (3-fluorophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide .
Analog Beispiel 1 aus 2,92 g (10 mmol) 2-(3-Fluorphenyl)-1,2-benzisoselenazol-3(2H)-on und 0,5 ml 30-%igem Wasserstoffperoxid in 50 ml Dichlormethan.Analogously to Example 1 from 2.92 g (10 mmol) 2- (3-fluorophenyl) -1,2-benzisoselenazol-3 (2H) -one and 0.5 ml of 30% hydrogen peroxide in 50 ml of dichloromethane.
Ausbeute: 2,85 g (92,5 % d.Th.), Fp. 165-166"C Beispiel 10 2-(3-Chlorphenyl)-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 2.85 g (92.5% of theory), melting point 165-166 "C Example 10 2- (3-chlorophenyl) -1,2-benzisoselenazol-3 (2H) -one-Se-oxide .
Analog Beispiel 1 aus 3,08 g (10 mmol) 2-(3-Chlorphenyl)-1,2-benzisoselenazol-3(2H)-on und 0,5 ml 30-%igem Wasserstoffperoxid in 50 ml Dichlormethan.Analogously to Example 1 from 3.08 g (10 mmol) 2- (3-chlorophenyl) -1,2-benzisoselenazol-3 (2H) -one and 0.5 ml of 30% hydrogen peroxide in 50 ml of dichloromethane.
Ausbeute: 3,0 y (92,5 % d.Th.), Fp. 180-183"C Beispiel 11 2-Phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 3.0 y (92.5% of theory), melting point 180-183 "C example 11 2-Phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide.
Analog Beispiel 1 aus 2,74 g (10 mmol) 2-Phenyl-1,2-benzisoselenazol-3(2H)-on und 0,5 ml 3Q%igem Wasserstoffperoxid in 50 ml Dichlormethan.Analogously to Example 1 from 2.74 g (10 mmol) of 2-phenyl-1,2-benzisoselenazol-3 (2H) -one and 0.5 ml 3Q% hydrogen peroxide in 50 ml dichloromethane.
Ausbeute: 2,7 g (93 % d.Th.), Fp. 200°C (Zers.) Beispiel 12 7-MethOxy-2-phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 2.7 g (93% of theory), melting point 200 ° C. (decomp.) Example 12 7-Methoxy-2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide .
Analog Beispiel 1 aus 3,04 (10 mmol) 7-Methoxy-2-phenyl-1,2-benzisoselenazol-3(2H)-on und 0,5 ml 30-%igem Wasserstoffperoxid in 50 ml Dichlormethan.Analogously to Example 1 from 3.04 (10 mmol) 7-methoxy-2-phenyl-1,2-benzisoselenazol-3 (2H) -one and 0.5 ml of 30% hydrogen peroxide in 50 ml of dichloromethane.
Ausbeute: 3,0 g (93,7 % d.Th.), Fp: 122-125°C Beispiel 13 5-Chlor-2-phenyl-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 3.0 g (93.7% of theory), mp: 122-125 ° C. Example 13 5-chloro-2-phenyl-1,2-benzisoselenazol-3 (2H) -one-Se-oxide .
Analog Beispiel 1 aus 3,08 g (10 mmol) 5-Chlor-2-phenyl-1,2-benzisoselenazol-3(2H)-on und 0,5 ml 30-%igem Wasserstoffperoxid in 50 ml Dichlormethan.Analogously to Example 1 from 3.08 g (10 mmol) of 5-chloro-2-phenyl-1,2-benzisoselenazol-3 (2H) -one and 0.5 ml of 30% hydrogen peroxide in 50 ml of dichloromethane.
Ausbeute: 3,1 g (95,5 % d.Th.), Fp. 268-272"C Beispiel 14 2-ga-(1-Carboxyethyl)-phenyl7-1,2-benzisoselenazol-3(2H)-on-Se-oxid.Yield: 3.1 g (95.5% of theory), melting point 268-272 "C Example 14 2-ga- (1-carboxyethyl) -phenyl7-1,2-benzisoselenazol-3 (2H) -one -Se-oxide.
Analog Beispiel 1 aus 1 g (2,88 mmol) 2-ZZ-(1-Carboxyethyl)-phenyl]-1,2-benzisoselenazol-3(2H)-on und 0,32 ml 30-%igem Wasserstoffperoxid in 60 ml Dichlormethan.Analogously to example 1 from 1 g (2.88 mmol) 2-ZZ- (1-carboxyethyl) -phenyl] -1,2-benzisoselenazol-3 (2H) -one and 0.32 ml of 30% hydrogen peroxide in 60 ml of dichloromethane.
Ausbeute: 0,61 g (58,6 % d.Th.), Fp. 235°C (Zers.)Yield: 0.61 g (58.6% of theory), melting point 235 ° C. (decomp.)
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843444135 DE3444135A1 (en) | 1984-12-04 | 1984-12-04 | Selenoxides, process for their preparation and pharmaceutical preparations containing them |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843444135 DE3444135A1 (en) | 1984-12-04 | 1984-12-04 | Selenoxides, process for their preparation and pharmaceutical preparations containing them |
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| Publication Number | Publication Date |
|---|---|
| DE3444135A1 true DE3444135A1 (en) | 1986-06-05 |
| DE3444135C2 DE3444135C2 (en) | 1992-12-10 |
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| Application Number | Title | Priority Date | Filing Date |
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| DE19843444135 Granted DE3444135A1 (en) | 1984-12-04 | 1984-12-04 | Selenoxides, process for their preparation and pharmaceutical preparations containing them |
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| Country | Link |
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| DE (1) | DE3444135A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0701554B1 (en) * | 1994-04-07 | 2001-06-27 | OXIS Isle of Man, Limited | Novel compounds having a benzisoselen-azoline and -azine structure, method for preparing same and therapeutic uses thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3027075A1 (en) * | 1980-07-17 | 1982-02-18 | A. Nattermann & Cie GmbH, 5000 Köln | BENZISOSELENAZOLONE, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM |
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1984
- 1984-12-04 DE DE19843444135 patent/DE3444135A1/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3027075A1 (en) * | 1980-07-17 | 1982-02-18 | A. Nattermann & Cie GmbH, 5000 Köln | BENZISOSELENAZOLONE, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM |
| DE3027075C2 (en) * | 1980-07-17 | 1989-05-18 | A. Nattermann & Cie Gmbh, 5000 Koeln, De |
Non-Patent Citations (2)
| Title |
|---|
| Biochem. Pharmacol. 33(1984), 3235-3239 * |
| Biochem. Pharmacol. 33(1984), 3241-3245 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0701554B1 (en) * | 1994-04-07 | 2001-06-27 | OXIS Isle of Man, Limited | Novel compounds having a benzisoselen-azoline and -azine structure, method for preparing same and therapeutic uses thereof |
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| Publication number | Publication date |
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| DE3444135C2 (en) | 1992-12-10 |
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