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DE2127267A1 - 2-amino-4,5,7,8-tetrahydro-6h-thiazolo-or oxazolo(5,4-d) - azepines - as hypotensive, antiphlogistic, sedative and bechic agents - Google Patents

2-amino-4,5,7,8-tetrahydro-6h-thiazolo-or oxazolo(5,4-d) - azepines - as hypotensive, antiphlogistic, sedative and bechic agents

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Publication number
DE2127267A1
DE2127267A1 DE19712127267 DE2127267A DE2127267A1 DE 2127267 A1 DE2127267 A1 DE 2127267A1 DE 19712127267 DE19712127267 DE 19712127267 DE 2127267 A DE2127267 A DE 2127267A DE 2127267 A1 DE2127267 A1 DE 2127267A1
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DE
Germany
Prior art keywords
acid
general formula
benzyl
urea
tetrahydro
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
DE19712127267
Other languages
German (de)
Inventor
Gerhart Dipl Chem Dr Kleemann Manfred Dipl Chem Dr Grell Wolfgang Dipl Chem Dr Ballhause Helmut 7950 Biberach Gnss
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim Pharma GmbH and Co KG
Original Assignee
Dr Karl Thomae GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dr Karl Thomae GmbH filed Critical Dr Karl Thomae GmbH
Priority to DE19712127267 priority Critical patent/DE2127267A1/en
Priority to BG018197A priority patent/BG17968A3/en
Priority to BG019141A priority patent/BG17785A3/en
Priority to BG019142A priority patent/BG17786A3/en
Priority to RO70457A priority patent/RO59127A/ro
Priority to RO70468A priority patent/RO59129A/ro
Priority to RO67900A priority patent/RO60635A/ro
Priority to ES393881A priority patent/ES393881A1/en
Priority to US00169065A priority patent/US3804849A/en
Priority to RO70469A priority patent/RO59925A/ro
Priority to CH1180571A priority patent/CH571003A5/xx
Priority to DK394071A priority patent/DK136654C/en
Priority to CS5856A priority patent/CS178084B2/cs
Priority to HUTO858A priority patent/HU162343B/hu
Priority to IL37492A priority patent/IL37492A/en
Priority to JP46061588A priority patent/JPS5246236B1/ja
Priority to AT711071A priority patent/AT310174B/en
Priority to FI2265/71A priority patent/FI54925C/en
Priority to NO3034/71A priority patent/NO131887C/no
Priority to FR7129692A priority patent/FR2102192B1/fr
Priority to YU2084/71A priority patent/YU35027B/en
Priority to PL1971150004D priority patent/PL85080B1/pl
Priority to GB3816071A priority patent/GB1321509A/en
Priority to CA120,522A priority patent/CA965423A/en
Priority to IE1027/71A priority patent/IE35517B1/en
Priority to NLAANVRAGE7111176,A priority patent/NL168516C/en
Priority to BE771330A priority patent/BE771330A/xx
Priority to SE7110347A priority patent/SE380529B/en
Priority to AU32411/71A priority patent/AU462319B2/en
Priority to ES396454A priority patent/ES396454A1/en
Priority to ES396453A priority patent/ES396453A1/en
Publication of DE2127267A1 publication Critical patent/DE2127267A1/en
Priority to US435719A priority patent/US3907996A/en
Priority to YU2884/78A priority patent/YU42168B/en
Priority to YU2882/78A priority patent/YU40542B/en
Priority to YU2883/78A priority patent/YU35029B/en
Priority to YU2881/78A priority patent/YU35028B/en
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

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

Abstract

Cpds (I) and their salts. (where R1 is H, 1-4C alkyl opt. substd. by OH, allyl, cycloalkyl, hexahydrobenzyl, phenyl, phenethyl or benzyl opt. substd by 1 or 2 halogen, 1-3-MeO, Cf3 or 1-3C alkyl, R2 is (when X is S) H, 1-5C alkyl, allyl, cycloalkyl, phenyl, benzyl, or phenethyl, and (when X is O) H) are prepd by reacting a hexahydroazepin-4-one with a urea or thiourea in the presence of halogen or a halo hydroazepin-4-one with a urea or thiourea or a 4-alkoxy-tetrahydroazepine with a thiourea in the presence of a halogen or by reducing (I R1 or R2= acyl) by hydroxyalkylating (I R1=He with an epoxide or by diacylating a 6-acylamino deriv. of (I). Thus 1-benzyl-5-bromohexahydro-1H-azepinone-(4)-and thiourea gave (I R1=benzyl R2=N, X=S).

Description

Verfahren zur Herstellung von AzePin-Derivaten zusatz zum DBP.............(Patentanmeldung P 20 40 510.i17 Im DBP......(Aktenzeichen P 20 40 510.1) werden u. a. Azepin-Derivate der allgemeinen Formel in der R1 ein Wasserstoffatom, einen gegebenenfalls durch eine Hydroxylgruppe substituierten geradkettigen oder verzweigten Alkylrest mit 1-4 Kohlenstoffatomen, einen Allyl-, Cycloalkyl-, Hexahydrobenzyl-, Phenyl-, Phenyläthyl- oder Benzylrest, wobei der Benzylrest im Kern durch ein oder zwei Halogenatome, durch 1-3 Methoxygruppen, durch eine Trifluormethyl - oder Alkylgruppe mit 1-3 Kohlenstoffatomen substituiert sein kann, bedeutet, deren Säureadditionssalze mit physiologisch verträglichen anorganischen oder organischen Säuren sowie Verfahren zu ihrer Herstellung beschrieben.Process for the production of azePine derivatives in addition to the DBP ............. (patent application P 20 40 510.i17 In the DBP ...... (file number P 20 40 510.1), among other things, azepine Derivatives of the general formula in which R1 is a hydrogen atom, a straight-chain or branched alkyl radical with 1-4 carbon atoms optionally substituted by a hydroxyl group, an allyl, cycloalkyl, hexahydrobenzyl, phenyl, phenylethyl or benzyl radical, the benzyl radical in the nucleus by one or two halogen atoms , can be substituted by 1-3 methoxy groups, by a trifluoromethyl or alkyl group with 1-3 carbon atoms, means whose acid addition salts with physiologically compatible inorganic or organic acids and processes for their preparation are described.

Diese Verbindungen weisen wertvolle pharmakologische Eigenschaften auf, insbesondere besitzen sie eine hustenstillende neben einer,sedierenden und blutzuckersenkenden Wirksamkeit.These compounds have valuable pharmacological properties on, in particular, they have a cough suppressant in addition to a, sedative and blood sugar lowering effectiveness.

Es wurde nun gefunden, daß sich die Verbindungen der allgemeinen Formel I auch nach folgendem Verfahren herstellen lassen: Umsetzung eines halogenwasserstoffsauren Salzes eines 5-Halogen-azepinons-(4) der allgemeinen Formel in der R1 wie eingangs definiert iat und Hal ein Chlor-, Brom- oder Jodatom darstellt, mit Harnstoff in einem Lösungsmittel.It has now been found that the compounds of the general formula I can also be prepared by the following process: Reaction of a hydrohalic acid salt of a 5-halo-azepinone- (4) of the general formula in which R1 as defined at the outset and Hal represents a chlorine, bromine or iodine atom, with urea in a solvent.

Die Umsetzung erfolgt in einem Lösungsmittel wie Äthanol, Isopropanol, tertXutanol, Eisessig, Dioxan, Dimethylformamid oder einem Gemisch der erwähnten Lösungsmittel vorzugsweise bei Temperaturen bis zur Siedetemperatur des verwendeten Lösungsmittel und'gegebenenfalls in Gegenwart einer Säure wie Eisessig.The reaction takes place in a solvent such as ethanol, isopropanol, tertXutanol, glacial acetic acid, dioxane, dimethylformamide or a mixture of the mentioned Solvent preferably at temperatures up to the boiling point of the one used Solvent and optionally in the presence of an acid such as glacial acetic acid.

Die erhaltenen Verbindungen können gewünschtenfalls nach üblichen Methoden in ihr hysiologisch verträglichen Säureadditionssalze mit einer anorganischen oder organischen Säure überführt werden. Als Säuren kommen beispielsweise Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Weinsäure, Bernsteinsäure, Zitronensäure, Adipinsäure, Embonsäure, Fumarsäure oder Maleinsäure in Betracht.The compounds obtained can, if desired, by customary Methods in her physiologically compatible acid addition salts with an inorganic one or organic acid. Examples of acids are hydrochloric acid, Hydrobromic acid, sulfuric acid, phosphoric acid, tartaric acid, succinic acid, citric acid, Adipic acid, emboxylic acid, fumaric acid or maleic acid can be considered.

Die als Ausgangsstoffe verwendeten 5-Halogen-azepinone-(4) der allgemeinen Formel II erhält man durch Halogenierung der entsprechenden Aæepinone-(4) in Eisessig mit der äquimolaren Menge Chlor, Brom oder Jod. Die hierfür verwendeten Azepinone-(4) sind teilweise literaturbekannt (Ak. Yokoo et al., Bull. Chem. Soc.The 5-halo-azepinone- (4) used as starting materials of the general Formula II is obtained by halogenating the corresponding Aæepinone- (4) in glacial acetic acid with the equimolar amount of chlorine, bromine or iodine. The azepinones used for this (4) are partially known from the literature (Ak. Yokoo et al., Bull. Chem. Soc.

Japan 29, 631 (1959)). Die bisher nicht beschriebenen in 1-Stellung substituierten Azepinone-(4) erhält man durch Dieckmann-Kondensation (Organic Reactions, Volume 15, 1-203) von N-subætituierten-N-z2-Athoxy-carbonylEthyl2-4-aminobuttersäure-äthylestern, wobei als Kondensationsmittel vorzugsweise Kalium-tert.-butylat oder Natriumhydrid verwendet wird, und anschließender Verseifung und Decarboxylierung der als Zwischenprodukt erhaltenen 1-substituierten-Hexahydro-4H-azepinon- (4)-3 bzw. 5-(carbonsäure-äthylester-Gemischen in Gegenwart von Säuren.Japan 29, 631 (1959)). Those not previously described in 1-position substituted azepinone- (4) are obtained by Dieckmann condensation (Organic Reactions, Volume 15, 1-203) of N-substituted-N-z2-ethoxy-carbonylEthyl2-4-aminobutyric acid ethyl esters, the preferred condensing agent being potassium tert-butoxide or sodium hydride is used, and subsequent saponification and decarboxylation of the intermediate product obtained 1-substituted-hexahydro-4H-azepinon- (4) -3 or 5- (carboxylic acid ethyl ester mixtures in the presence of acids.

Die nachfolgenden Beispiele sollen die Erfindung näher erläutern: Beispiel 1 2-Amino-6-äthyl-4,5,7,8-tetrahydro-6H-oxazolo[5,4-d7az epindihydrochlorid 9 g (30 m Mol) 1-Äthyl-5-brom-hexahydro-4H-azepinon-(4) hydrobromid (Schmelzpunkt: 1420C) und 9 g (150 m Mol) Harnstoff werden in 30 ml Isopropanol zwei Stunden zum Sieden erhitzt, während dieser Zeit geht die anfängliche Suspension in eine Lösung Ubcr. Nach Abdestillieren des Lösungsmittels wird der Destillationsrückstand in Wasser gelöst, mit Natronlauge auf pH 12 gestellt und mit Chloroform extrahiert. Die aus den getrockneten Chloroformextrakten erhaltene Rohbase wird aus Aceton umkristallisiert.The following examples are intended to explain the invention in more detail: example 1 2-Amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo [5,4-d7az epine dihydrochloride 9 g (30 m mol) 1-ethyl-5-bromo-hexahydro-4H-azepinone- (4) hydrobromide (melting point: 1420C) and 9 g (150 m mol) of urea are boiled in 30 ml of isopropanol for two hours heated, during this time the initial suspension goes into a solution Ubcr. After the solvent has been distilled off, the distillation residue is dissolved in water dissolved, adjusted to pH 12 with sodium hydroxide solution and extracted with chloroform. From the crude base obtained from the dried chloroform extracts is recrystallized from acetone.

Ausbeute: 1,4 g (26 % der Theorie), Schmelzpunkt: 152-1530C C9H15N3° (181,23) Ber.: C 59,60 H 8,35 N 23,20 Gef.: C 59,60 H 8,38 N 23,45 Zur terführung in das Dihydrochlorid wird die Base in 4 ml Methanol/Aceton (1/3) suspendiert und Salzsäure bis zur Sättigung eingeleitet, dabei bildet sich eine Lösung, aus der das Dihydrochlorid beim Erkalten auskristallisiert0 Ausbeute: 96 % der Theorie, Schmelzpunkt: 217-2190C (Zers.) C9H15N3O Ber.: C 42,56 H 6,74 N 16,54 Gef.: C 42,60 H 6,82 N 16,68 Beispiel 2 2-Amino-6-propyl-4,5,7,8-tetrahydro-oxazolo[5,4-d]azepindihydrochlorid Hergestellt analog Beispiel 1 aus 1-Propyl-5-brom-hexa'hydro-4H-azepinon-(4)-hydrobromid und Harnstoff in tert. Butanol.Yield: 1.4 g (26% of theory), melting point: 152-1530C C9H15N3 ° (181.23) Calc .: C 59.60 H 8.35 N 23.20 Found: C 59.60 H 8.38 N 23.45 the base is suspended in 4 ml of methanol / acetone (1/3) and in the dihydrochloride Hydrochloric acid is introduced to saturation, a solution is formed from which the dihydrochloride crystallizes out on cooling 0 Yield: 96% of theory, Melting point: 217-2190C (dec.) C9H15N3O Calculated: C 42.56 H 6.74 N 16.54 Found: C 42.60 H 6.82 N 16.68 Example 2 2-Amino-6-propyl-4,5,7,8-tetrahydro-oxazolo [5,4-d] azepine dihydrochloride Prepared analogously to Example 1 from 1-propyl-5-bromo-hexa'hydro-4H-azepinone- (4) -hydrobromide and urea in tert. Butanol.

Auæbeute: 18 96 der Theorie, Schmelzpunkt: 221°C (Zers) Beispiel 3 2-Amino-6-isopropvl-4,5,7,8-tetrahydro-oxazolo[5,4-d]azepin Hergestellt analog Beispiel 1 aus 1-Isopropyl-5-brom-hexa'hydro-4H-azepinon-(4)-hydrobromid und Harnstoff in Isopropanol/ Eisessig (30 : 1).Yield: 18 96 of theory, melting point: 221 ° C. (decomposition), Example 3 2-Amino-6-isopropyl-4,5,7,8-tetrahydro-oxazolo [5,4-d] azepine Prepared analogously to the example 1 from 1-isopropyl-5-bromo-hexa'hydro-4H-azepinone- (4) -hydrobromide and urea in Isopropanol / glacial acetic acid (30: 1).

Ausbeute: 23 % der Theorie, Schmelzpunkt: 1100C Beispiel 4 2-Amino-6-n-butyl-4,5,7,8-tetrahydro-6H-oxazolo[5,4-d]azepindihYdrochlorid Hergestellt analog Beispiel 1 aus 1-n-Butyl-5-brom-hexahydro-4H-azepinon-(4)-hydrobromid und Harnstoff in Isopropanol.Yield: 23% of theory, melting point: 1100 ° C. Example 4 2-Amino-6-n-butyl-4,5,7,8-tetrahydro-6H-oxazolo [5,4-d] azepinedihydrochloride Manufactured analogously to Example 1 from 1-n-butyl-5-bromo-hexahydro-4H-azepinone- (4) -hydrobromide and urea in isopropanol.

Ausbeute: 25 % der Theorie, Schmelzpunkt: 2100C (Zers.) Beispiel 5 2-Amino-6-isobutyl-4,5,7,8-tetrahydro-6H-oxazolo[5,4-d]azepindihydrochlorid Hergestellt analog Beispiel 1 aus 1-Isobutyl-5-brom-hexa'hydro-4H-azepinon-(4)-hydrobromid und Harnstoff in tert. Butanol.Yield: 25% of theory, melting point: 2100C (decomp.) example 5 Prepared 2-amino-6-isobutyl-4,5,7,8-tetrahydro-6H-oxazolo [5,4-d] azepine dihydrochloride analogously to Example 1 from 1-isobutyl-5-bromo-hexa'hydro-4H-azepinone- (4) -hydrobromide and Urea in tert. Butanol.

Ausbeute: 19 96 der Theorie, Schmelzpunkt: 2100C (Zers.) Beispiel 6 2-Amino-6-allyl-4f5,7,8-tetrahydro-6H oxazoloz5,4-dzazepindihydrochlorid Hergestellt analog Beispiel 1 aus 1-Allyl-5-brom-hexahydro-4H-azepinon-(4)-hydrobromid und Harnstoff in Isopropanol.Yield: 19 96 of theory, melting point: 2100 ° C. (decomp.) Example 6 2-Amino-6-allyl-4f5,7,8-tetrahydro-6H oxazoloz5,4-dzazepine dihydrochloride Prepared analogously to Example 1 from 1-allyl-5-bromo-hexahydro-4H-azepinone- (4) -hydrobromide and urea in isopropanol.

Ausbeute: 14 ffi der Theorie, Schmelzpunkt: 2090C (Zers.) Beispiel 7 2-Amino-6-benzyl-4,5,7,8-tetrahydro-6H-oxazolo[5,4-d]azepindihydrochlorid Hergestellt analog Beispiel 1 aus 1-Benzyl-5-brom-hexahydro-13, [5,4-d]azepin-hydrobromid und Harnstoff in Isopropanol/Eisessig.Yield: 14 ff of theory, melting point: 2090C (decomp.) Example 7 Prepared 2-amino-6-benzyl-4,5,7,8-tetrahydro-6H-oxazolo [5,4-d] azepine dihydrochloride analogously to Example 1 from 1-benzyl-5-bromo-hexahydro-13, [5,4-d] azepine hydrobromide and Urea in isopropanol / glacial acetic acid.

Ausbeute: 24 % der Theorie, Schmelzpunkt: 2090C (Zers.) Beispiel 8 2-Amino-6-benzyl-4,5,7,8-tetrahydro-6H-oxazolo[5,4-d]azepindihydrochlorid Hergestellt analog Beispiel 1 aus 1-Hexahydrobenzyl-5-bromhexahydro-4H-azepinon-(4)-hydrobromid und Harnstoff in Isopropanol.Yield: 24% of theory, melting point: 2090C (decomp.) example 8 Prepared 2-amino-6-benzyl-4,5,7,8-tetrahydro-6H-oxazolo [5,4-d] azepine dihydrochloride analogous to Example 1 from 1-hexahydrobenzyl-5-bromohexahydro-4H-azepinone- (4) -hydrobromide and urea in isopropanol.

Ausbeute: 12 % der Theorie, Schmelzpunkt: 2290C (Zers.) Beispiel 9 2-Amino-6-(4-methyl-benzyl)-4,5,7,8-tetrahydro-6H-oxazolo[5,4-d]-azepin-dihydrochlorid Hergestellt analog Beispiel 1 aus 1-(4-Methyl-benzyl)-5-bromhexahydro-4H-azepinon-(4)-hydrobromid und Harnstoff in Dimethylformamid.Yield: 12% of theory, melting point: 2290 ° C. (decomp.) Example 9 2-Amino-6- (4-methyl-benzyl) -4,5,7,8-tetrahydro-6H-oxazolo [5,4-d] -azepine dihydrochloride Prepared analogously to Example 1 from 1- (4-methyl-benzyl) -5-bromohexahydro-4H-azepinone- (4) -hydrobromide and urea in dimethylformamide.

Ausbeute: 15 % der Theorie, Schmelzpunkt: t 2040C (Zers)Yield: 15% of theory, melting point: t 2040C (decomposition)

Claims (4)

Patentansprüche ============= 1. Verfahren zur Herstellung von Azepin-Derivaten der allge-- meinen Formel in der R1 ein Wasserstoffatom, einen gegebenenfalls durch eine Hydroxylgruppe substituierten geradkettigen oder verzweigten Alkylrest mit 1-4 Kohlenstoffatomen, einen Allyl-, Cycloalkyl-, Hexahydrobenzyl-, Phenyl-, Phenyläthyl- oder Benzylrest, wobei der Benzylrest im Kern durch ein oder zwei Halogenatome, durch 1-3 Methoxygruppen, durch eine Trifluormethyl- oder Alkylgruppe mit 1-3 Kohlenstoffatomen substituiert sein kann, bedeutet, sowie von deren physiologisch verträglichen Säuren additionssalzen gemäß DJ3P. (Aktenzeichen P 20 40 510.1), dadurch gekennzeichnet, daß ein halogenwasserstoffsaures Salz eines 5-Halogen-az'epinons-(4) der allgemeinen Formel in der R1 wie eingangs definiert ist und Hal ein Chlor-, Brom- oder Jodatom darstellt, mit Harnstoff in einem Lösungsmittel umgesetzt wird und die erhaltene Verbindung der allgemeinen Formel I gewünschtenfalls in ein Salz mit einer physiologisch verträglichen anorganischen oder organischen Säure überführt wird.Claims ============= 1. Process for the preparation of azepine derivatives of the general formula in which R1 is a hydrogen atom, a straight-chain or branched alkyl radical with 1-4 carbon atoms optionally substituted by a hydroxyl group, an allyl, cycloalkyl, hexahydrobenzyl, phenyl, phenylethyl or benzyl radical, the benzyl radical in the nucleus by one or two halogen atoms , can be substituted by 1-3 methoxy groups, by a trifluoromethyl or alkyl group with 1-3 carbon atoms, means, as well as of their physiologically acceptable acids, addition salts according to DJ3P. (File number P 20 40 510.1), characterized in that a hydrohalic acid salt of a 5-halo-az'epinons- (4) of the general formula in which R1 is defined as above and Hal represents a chlorine, bromine or iodine atom, is reacted with urea in a solvent and the compound of general formula I obtained is converted, if desired, into a salt with a physiologically acceptable inorganic or organic acid. 2. Verfahren gemäß Anspruch 1, dadurch gennzeichnet, daß die Umsetzung in einem Lösungsmittel wie Äthanol, Isopropanol, tert.-Butanol, Eisessig, Dioxan, Dimethylformamid oder einem Gemisch der erwähnten Lösungsmittel durchgeführt wird.2. The method according to claim 1, characterized in that the implementation in a solvent such as ethanol, isopropanol, tert-butanol, glacial acetic acid, dioxane, Dimethylformamide or a mixture of the solvents mentioned is carried out. 3. Verfahren gemäß Anspruch 1 und 2, dadurch gekennzeichnet, daß die Umsetzung bei Temperaturen bis zur Siedetemperatur des verwendeten Lösungsmittels durchgeführt wird.3. The method according to claim 1 and 2, characterized in that the Implementation at temperatures up to the boiling point of the solvent used is carried out. 4. Verfahren gemäß Anspruch 1, 2 und 3, dadurch gekennzeichnet, daß die Umsetzung in Gegenwart einer Säure wie Eisessig durchgeführt wird.4. The method according to claim 1, 2 and 3, characterized in that the reaction is carried out in the presence of an acid such as glacial acetic acid.
DE19712127267 1970-08-14 1971-06-02 2-amino-4,5,7,8-tetrahydro-6h-thiazolo-or oxazolo(5,4-d) - azepines - as hypotensive, antiphlogistic, sedative and bechic agents Withdrawn DE2127267A1 (en)

Priority Applications (36)

Application Number Priority Date Filing Date Title
DE19712127267 DE2127267A1 (en) 1971-06-02 1971-06-02 2-amino-4,5,7,8-tetrahydro-6h-thiazolo-or oxazolo(5,4-d) - azepines - as hypotensive, antiphlogistic, sedative and bechic agents
BG018197A BG17968A3 (en) 1970-08-14 1971-07-30 METHOD FOR OBTAINING AZEPINE DERIVATIVES
BG019141A BG17785A3 (en) 1970-08-14 1971-07-30 METHOD FOR OBTAINING NEW AZETINE DERIVATIVES
BG019142A BG17786A3 (en) 1970-08-14 1971-07-30 METHOD FOR OBTAINING NEW AZEPINE DERIVATIVES
RO70457A RO59127A (en) 1970-08-14 1971-08-04
RO70468A RO59129A (en) 1970-08-14 1971-08-04
RO67900A RO60635A (en) 1970-08-14 1971-08-04
ES393881A ES393881A1 (en) 1970-08-14 1971-08-04 2-amino-4,5,7,8-tetrahydro-6h-thiazolo or oxazolo(5,4-d)azepines and salts
US00169065A US3804849A (en) 1970-08-14 1971-08-04 2-amino-4,5,7,8-tetrahydro-6h-thiazolo or oxazolo(5,4-d)azepines and salts
RO70469A RO59925A (en) 1970-08-14 1971-08-04
CH1180571A CH571003A5 (en) 1970-08-14 1971-08-11
DK394071A DK136654C (en) 1970-08-14 1971-08-12 ANALOGICAL PROCEDURE FOR THE PREPARATION OF AZEPIN DERIVATIVES OR SALTS THEREOF
CS5856A CS178084B2 (en) 1970-08-14 1971-08-12
HUTO858A HU162343B (en) 1970-08-14 1971-08-12
IL37492A IL37492A (en) 1970-08-14 1971-08-12 6h-oxazolo(or thiazolo)(5,4-d)-azepine derivatives,their salts,preparation thereof and pharmaceutical compositions containing them
FI2265/71A FI54925C (en) 1970-08-14 1971-08-13 PROCEDURE FOR THE PREPARATION OF OIL BLOOD TRYCYCLES 2-AMINO-4,5,7,8-TETRAHYDRO-6H-THIAZOLO-OCH OXAZOLO (5,4-D) AZEPINER
BE771330A BE771330A (en) 1970-08-14 1971-08-13
JP46061588A JPS5246236B1 (en) 1970-08-14 1971-08-13
NO3034/71A NO131887C (en) 1970-08-14 1971-08-13
FR7129692A FR2102192B1 (en) 1970-08-14 1971-08-13
YU2084/71A YU35027B (en) 1970-08-14 1971-08-13 Process for preparing novel oxazolo-or thiazoloazepine derivatives
PL1971150004D PL85080B1 (en) 1970-08-14 1971-08-13
GB3816071A GB1321509A (en) 1970-08-14 1971-08-13 Azepine derivatives
CA120,522A CA965423A (en) 1970-08-14 1971-08-13 Azepine-derivatives
IE1027/71A IE35517B1 (en) 1970-08-14 1971-08-13 Azepine derivatives
NLAANVRAGE7111176,A NL168516C (en) 1970-08-14 1971-08-13 METHOD FOR PREPARING A PHARMACEUTICALLY BASED ON A NITROGEN CONTAINED NITROGEN CONTAINING NITROGEN CONTAINED WITH A NITROGEN GROUP AND / OR A PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALT THEREFOR AND ITS PROPERTY THEREFOR AND ITS PROCESS.
AT711071A AT310174B (en) 1970-08-14 1971-08-13 Process for the preparation of new azepine derivatives and their acid addition salts
SE7110347A SE380529B (en) 1970-08-14 1971-08-13 ANALOGICAL PROCEDURES FOR THE PREPARATION OF NEW AZEPINE DERIVATIVES
AU32411/71A AU462319B2 (en) 1970-08-14 1971-08-16 Azepine derivatives
ES396454A ES396454A1 (en) 1970-08-14 1971-10-28 PROCEDURE FOR THE PREPARATION OF AZEPINE DERIVATIVES.
ES396453A ES396453A1 (en) 1970-08-14 1971-10-28 2-amino-4,5,7,8-tetrahydro-6h-thiazolo or oxazolo(5,4-d)azepines and salts
US435719A US3907996A (en) 1970-08-14 1974-01-23 Pharmaceutical composition containing a 2-amino-4,5,7,8-tetrahydro-6H-thiazolo or -oxazolo 5,4-D azepine and method of use
YU2884/78A YU42168B (en) 1970-08-14 1978-12-06 Process for preparing new azepine derivatives
YU2882/78A YU40542B (en) 1970-08-14 1978-12-08 Process for preparing new azepine derivatives
YU2883/78A YU35029B (en) 1970-08-14 1978-12-08 Process for preparing novel azepine derivatives
YU2881/78A YU35028B (en) 1970-08-14 1978-12-08 Process for preparing novel azepine derivatives

Applications Claiming Priority (1)

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DE19712127267 DE2127267A1 (en) 1971-06-02 1971-06-02 2-amino-4,5,7,8-tetrahydro-6h-thiazolo-or oxazolo(5,4-d) - azepines - as hypotensive, antiphlogistic, sedative and bechic agents

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5180721A (en) * 1989-05-22 1993-01-19 Allergan, Inc. Combinations of selective alpha-adrenergic agonists and antagonists useful in lowering intraocular pressure
US5252595A (en) * 1990-02-28 1993-10-12 Allergan, Inc. Method for reducing or maintaining intraocular pressure in the mammalian eye by administering pharmaceutical compositions containing 2-(2-alkylphenylamino)-oxazolines, 2-(2-alkylphenylamino)-thiazolines and 2-(2-alkylphenylamino)-imidazolines
US5281591A (en) * 1989-05-22 1994-01-25 Allergan, Inc. Combinations of selective alpha-adrenergic agonists and antagonists useful in lowering intraocular pressure
US5580892A (en) * 1993-10-22 1996-12-03 Allergan Method for using 2-(2-alkylphenylamino)-oxazolines as adrenergic agents

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In Betracht gezogene ältere Anmeldung: DE-OS 20 40 510.1 *
R.C. Elderfield Heterocyclic Compounds Vo 25, 1957, S. 307-308 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5180721A (en) * 1989-05-22 1993-01-19 Allergan, Inc. Combinations of selective alpha-adrenergic agonists and antagonists useful in lowering intraocular pressure
US5281591A (en) * 1989-05-22 1994-01-25 Allergan, Inc. Combinations of selective alpha-adrenergic agonists and antagonists useful in lowering intraocular pressure
US5252595A (en) * 1990-02-28 1993-10-12 Allergan, Inc. Method for reducing or maintaining intraocular pressure in the mammalian eye by administering pharmaceutical compositions containing 2-(2-alkylphenylamino)-oxazolines, 2-(2-alkylphenylamino)-thiazolines and 2-(2-alkylphenylamino)-imidazolines
US5580892A (en) * 1993-10-22 1996-12-03 Allergan Method for using 2-(2-alkylphenylamino)-oxazolines as adrenergic agents
US5708015A (en) * 1993-10-22 1998-01-13 Allergan Method for using pharmaceutical compositions containing 2-(2-alkyphenyl-amino)-thiazolines as adrenergic agents

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