DE1950351B2 - 1 - (2-Cyano-5-methylphenoxy) -2-hydroxy-3-alkylaminopropanes, process for their preparation and pharmaceuticals containing them - Google Patents

1 - (2-Cyano-5-methylphenoxy) -2-hydroxy-3-alkylaminopropanes, process for their preparation and pharmaceuticals containing them

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Publication number
DE1950351B2
DE1950351B2 DE19691950351 DE1950351A DE1950351B2 DE 1950351 B2 DE1950351 B2 DE 1950351B2 DE 19691950351 DE19691950351 DE 19691950351 DE 1950351 A DE1950351 A DE 1950351A DE 1950351 B2 DE1950351 B2 DE 1950351B2
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DE
Germany
Prior art keywords
hydroxy
methylphenoxy
cyano
formula
acid
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.)
Granted
Application number
DE19691950351
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German (de)
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DE1950351A1 (en
DE1950351C3 (en
Inventor
A Engelhardt
H Koppe
K Zeile
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CH Boehringer Sohn AG and Co KG
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CH Boehringer Sohn AG and Co KG
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Priority to BG018263A priority Critical patent/BG17528A3/en
Application filed by CH Boehringer Sohn AG and Co KG filed Critical CH Boehringer Sohn AG and Co KG
Priority to DE19691950351 priority patent/DE1950351C3/en
Priority to BG015085A priority patent/BG17590A3/en
Priority to CS646770A priority patent/CS162731B2/cs
Priority to BG018262A priority patent/BG17294A3/en
Priority to CH546221D priority patent/CH546221A/en
Priority to CH697273A priority patent/CH553166A/en
Priority to BG018264A priority patent/BG17295A3/en
Priority to CH697773A priority patent/CH553167A/en
Priority to CH697573A priority patent/CH542815A/en
Priority to CH546218D priority patent/CH546218A/en
Priority to BG018268A priority patent/BG17531A3/en
Priority to CH1461770A priority patent/CH542814A/en
Priority to BG018266A priority patent/BG17529A3/en
Priority to BG018261A priority patent/BG17527A3/en
Priority to BG015776A priority patent/BG17293A3/en
Priority to BG018265A priority patent/BG17296A3/en
Priority to CH546222D priority patent/CH546222A/en
Priority to CH546219D priority patent/CH546219A/en
Priority to CH696973A priority patent/CH555322A/en
Priority to CH546220D priority patent/CH546220A/en
Priority to ES384244A priority patent/ES384244A1/en
Priority to SU1705074A priority patent/SU400081A1/en
Priority to SU1481523A priority patent/SU361563A1/en
Priority to SU1705732A priority patent/SU423291A3/ru
Priority to SU1705733A priority patent/SU421182A3/en
Priority to SE1347570A priority patent/SE375094B/xx
Priority to SU1705040A priority patent/SU400082A1/en
Priority to SU1705730A priority patent/SU417938A3/en
Priority to PL17334370A priority patent/PL84637B1/en
Priority to PL14378570A priority patent/PL84252B1/en
Priority to PL17334270A priority patent/PL84642B1/en
Priority to DK505570A priority patent/DK128237B/en
Priority to JP8675670A priority patent/JPS501262B1/ja
Priority to SU1699774A priority patent/SU426360A3/en
Priority to SU1705731A priority patent/SU422137A3/en
Priority to YU244470A priority patent/YU34516B/en
Priority to AT900970A priority patent/AT302274B/en
Priority to AT1052371A priority patent/AT308072B/en
Priority to RO6726970A priority patent/RO59185A/ro
Priority to RO6728970A priority patent/RO58550A/ro
Priority to RO6727070A priority patent/RO58533A/ro
Priority to RO6726870A priority patent/RO58532A/ro
Priority to RO6727170A priority patent/RO59186A/ro
Priority to AT1053071A priority patent/AT306700B/en
Priority to AT1052671A priority patent/AT306696B/en
Priority to AT1052571A priority patent/AT306695B/en
Priority to AT1052971A priority patent/AT306699B/en
Priority to RO6727270A priority patent/RO58534A/ro
Priority to RO6461670A priority patent/RO56983A/ro
Priority to RO6727370A priority patent/RO58548A/ro
Priority to AT1052771A priority patent/AT306697B/en
Priority to RO6727470A priority patent/RO58549A/ro
Priority to AT1052471A priority patent/AT306694B/en
Priority to AT1052871A priority patent/AT306698B/en
Priority to AT1053171A priority patent/AT306701B/en
Publication of DE1950351A1 publication Critical patent/DE1950351A1/en
Priority to ES391141A priority patent/ES391141A1/en
Priority to ES391139A priority patent/ES391139A1/en
Priority to ES391136A priority patent/ES391136A1/en
Priority to ES391135A priority patent/ES391135A1/en
Priority to ES391140A priority patent/ES391140A1/en
Priority to ES391137A priority patent/ES391137A1/en
Priority to ES391138A priority patent/ES391138A1/en
Priority to ES391134A priority patent/ES391134A1/en
Priority to SU1699773A priority patent/SU503507A3/en
Publication of DE1950351B2 publication Critical patent/DE1950351B2/en
Application granted granted Critical
Publication of DE1950351C3 publication Critical patent/DE1950351C3/en
Expired legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/275—Nitriles; Isonitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/53—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and hydroxy groups bound to the carbon skeleton
    • E—FIXED CONSTRUCTIONS
    • E05—LOCKS; KEYS; WINDOW OR DOOR FITTINGS; SAFES
    • E05D—HINGES OR SUSPENSION DEVICES FOR DOORS, WINDOWS OR WINGS
    • E05D15/00—Suspension arrangements for wings
    • E05D15/40—Suspension arrangements for wings supported on arms movable in vertical planes
    • E05D15/44—Suspension arrangements for wings supported on arms movable in vertical planes with pivoted arms and vertically-sliding guides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Description

CNCN

(M)(M)

CH3
worin Z die GruppeCH 3
wherein Z is the group

CHCH

-CH,-CH,

NH,-RNH, -R

(111)(111)

worin R die in Anspruch 1 genannte Bedeutung besitzt, umsetzt, oder daß man
b) ein l-(2-Amino-5-methyl-phenoxy)-2-hydroxy-3-alkylaminopropan der Formel (IV)wherein R has the meaning given in claim 1, or that one
b) a l- (2-amino-5-methyl-phenoxy) -2-hydroxy-3-alkylaminopropane of the formula (IV)

0-CH2-CHOH-CH7-NHR0-CH 2 -CHOH-CH 7 -NHR

(IV)(IV)

worin R die in Anspruch 1 genannte Bedeutung besitzt, diazotiert und dann mit Kupfer(I)-cyanid umsetzt sowie gegebenenfalls die erhaltene Verbindung in ein physiologisch verträgliches Säureadditionssalz überführtwherein R has the meaning given in claim 1, diazotized and then with copper (I) cyanide converts and, if appropriate, the compound obtained into a physiologically acceptable acid addition salt convicted

4. Arzneimittel, gekennzeichnet durch einen Gehalt an 1 -(2-Cyano-5-methyl-phenoxy)-2-hydroxy-3-alkylaminopropanen oder deren Säureadditionssalzen nach Anspruch 1 als Wirkstoff neben gebräuchlichen Hilfsstoffen.4. Medicinal products, characterized by a content of 1 - (2-cyano-5-methyl-phenoxy) -2-hydroxy-3-alkylaminopropanes or their acid addition salts according to claim 1 as active ingredient in addition to customary auxiliaries.

Die Erfindung betrifft l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-alkylaminopropane und deren physiologisch verträgliche Säureadditionssalze, ein Verfahren zur Herstellung der erfindungsgemäQen Verbindungen sowie diese enthaltende Arzneimittel gemäß den Ansprüchen 1 bis 4.The invention relates to 1- (2-cyano-5-methylphenoxy) -2-hydroxy-3-alkylaminopropanes and their physiologically acceptable acid addition salts, a process for the preparation of the compounds according to the invention as well as medicaments containing them according to claims 1 to 4.

Die erfindungsgemäQen Verbindungen entsprechen der Formel (I)The compounds according to the invention correspond to the formula (I)

oder die Gruppe -CHOH-CH2-HaI (Hai = Halogenatom) bedeutet, mit einem Alkylamin der Formel (III)or the group -CHOH-CH 2 -HaI (Hai = halogen atom) means with an alkylamine of the formula (III)

CNCN

0-CH2-CH-CH2-NHR (I)0-CH 2 -CH-CH 2 -NHR (I)

OHOH

In dieser Formel bedeutet R einen Äthylrest oder einen Alkylrest mit 4 bis 6 C-Atomen.In this formula, R denotes an ethyl radical or an alkyl radical having 4 to 6 carbon atoms.

Die erfindungsgemäßen Verbindungen können in an sich bekannter Weise hergestellt werden durch
a) Umsetzung einer Verbindung der Formel (II),The compounds according to the invention can be prepared in a manner known per se by
a) reaction of a compound of formula (II),

(H)(H)

CH3
jo worin Z die GruppeCH 3
jo where Z is the group

-CH--CH-

CH2 CH 2

oder die Gruppe -CHOH-CH2-HaI (Hai = Halogenatom) bedeutet, mit einem Alkylamin der Formel (III)or the group -CHOH-CH 2 -HaI (Hai = halogen atom) means with an alkylamine of the formula (III)

NH,-RNH, -R

(III)(III)

worin R die obengenannte Bedeutung hat, oder
b) Diazotierung und anschließende Umsetzung mit Kupfer(I)-cyanid von 1 -(2-Amino-5-methylphenoxy)-2-hydroxy-3-alkyI-aminopropan der Formel (IV)wherein R has the abovementioned meaning, or
b) Diazotization and subsequent reaction with copper (I) cyanide of 1 - (2-amino-5-methylphenoxy) -2-hydroxy-3-alkyI-aminopropane of the formula (IV)

NH,NH,

0-CH2-CHOH-CH2-NHR (IV)0-CH 2 -CHOH-CH 2 -NHR (IV)

worin R die oben angegebene Bedeutung hatwherein R has the meaning given above

Das für die Durchführung der Verfahren benötigte Ausgangsmaterial ist zum Teil bereits bekannt, zum Teil kann es nach üblichen Verfahren gewonnen werden. So läßt sich das l-(2-Cyano-5-methylphenoxy)-2,3-epoxypropan der Formel II leicht durch Umsetzung von Epichlorhydrin mit 2-Cyano-5-methylphenol oder einem seiner Salze in alkalischem Medium darstellen. Das so erhaltene l-(2-Cyano-5-methylphenoxy)-2,3-epoxypropan läßt sich durch Umsetzung mit den entsprechenden Halogenwasserstoffsäuren in die Halogenhydrine der Formel II überführen.The starting material required to carry out the process is partly already known, partly it can be obtained by conventional methods. So can the 1- (2-cyano-5-methylphenoxy) -2,3-epoxypropane of formula II easily by reacting epichlorohydrin with 2-cyano-5-methylphenol or represent one of its salts in an alkaline medium. The l- (2-cyano-5-methylphenoxy) -2,3-epoxypropane thus obtained can be converted into the halohydrins by reaction with the corresponding hydrohalic acids of formula II convert.

Die Verbindungen der Formel IV enthalten bereits das fertige l-Phenoxy^-hydroxy-S-alkylaminopropan-Gerüst und lassen sich daher analog dem obenThe compounds of the formula IV already contain the finished l-phenoxy ^ -hydroxy-S-alkylaminopropane structure and can therefore be analogous to the above

beschriebenen Verfahren a), ausgehend von dem entsprechenden substituierten Phenol über das entsprechende l-Phenoxy-2,3-epoxypropan durch Umsetzung des letzteren mit einem Alkylamin der Formel III darstellen. Zur Herstellung solcher Verbindungen der Formel IV stellt man zweckmäßigerweise zunächst die entsprechende Nitroverbindung dar, die anschließend katalytisch reduziert werden kann.described method a), starting from the corresponding substituted phenol via the corresponding l-phenoxy-2,3-epoxypropane by reacting the latter with an alkylamine of the formula III represent. To prepare such compounds of the formula IV, it is expedient to first prepare the corresponding nitro compound, which can then be catalytically reduced.

Die erfindungsgemäßen Verbindungen besitzen an der CHOH-Gruppe ein asymmetrisches C-Atom und kommen daher als Racemat wie auch in Form der optischen Antipoden vor. Letztere können außer durch Racematentrennur.g mit üblichen Hilfssäuren, wie Dibenzoyl-D-weinsäure, Ditoluyl- D- weinsäure oder D-S-Bromcampher-e-sulfonsäure, auch durch Einsetzen von optisch aktivem Ausgangsmaterial erhalten werden.The compounds according to the invention have an asymmetric carbon atom on the CHOH group and therefore occur as a racemate as well as in the form of the optical antipodes. The latter can save through Racematentrennur.g with customary auxiliary acids such as dibenzoyl-D-tartaric acid, ditoluyl-D-tartaric acid or D-S-bromocamphor-e-sulfonic acid, also by onset from optically active starting material.

Die erfindungsgemäßen Substanzen der Formel I können in üblicher Weise in ihre physiologisch verträglichen Säureadditionssalze überführt werden. Geeignete Säuren sind beispielsweise Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Methansulfonsäure, Maleinsäure, Essigsäure, Oxalsäure, Milchsäure, Weinsäure, Bernsteinsäure oder 8-Chlortheophyllin.The substances of the formula I according to the invention can be converted into their physiological compatible acid addition salts are transferred. Suitable acids are, for example, hydrochloric acid, hydrobromic acid, Sulfuric acid, methanesulfonic acid, maleic acid, acetic acid, oxalic acid, lactic acid, tartaric acid, Succinic acid or 8-chlorotheophylline.

Tabelle ITable I.

Die Verbindungen der Formel I bzw. deren physiologisch verträgliche Säureadditionssalze haben im Tierversuch an Meerschweinchen hervorragende therapeutische, insbesondere ß-adrenolytische EigenschaftenThe compounds of the formula I or their physiologically acceptable acid addition salts have been tested on animals excellent therapeutic properties, especially ß-adrenolytic properties on guinea pigs

·> gezeigt und können daher beispielsweise zur Behandlung oder Prophylaxe von Erkrankungen der Herzkranzgefäße und zur Behandlung von Herzarrhythmien, insbesondere Tachycardien, in der Humanmedizin eingesetzt werden. Sie sind dabei strukturähnlichen·> Shown and can therefore be used, for example, for treatment or prophylaxis of diseases of the coronary arteries and for the treatment of cardiac arrhythmias, in particular tachycardia, are used in human medicine. They are structurally similar

in bekannten Verbindungen, wie beispielsweise dem l-(2-Cyano-3-methylphenoxy)-2-hydroxy-3-isopropylaminopropan und dem l-(2-Cyano-3-methylphenoxy)-2-hydroxy-3-tert.-butylaminopropan noch weitaus überlegen. Als ganz besonders wertvoll hat sich dabei das 1 -(2-Cyano-5-methylphenoxy)-2-hydroxy-3-tert.-butylaminopropan herausgestellt.in known compounds such as the 1- (2-cyano-3-methylphenoxy) -2-hydroxy-3-isopropylaminopropane and the 1- (2-cyano-3-methylphenoxy) -2-hydroxy-3-tert-butylaminopropane still far superior. 1 - (2-cyano-5-methylphenoxy) -2-hydroxy-3-tert.-butylaminopropane has proven to be particularly valuable exposed.

Die Einzeldosis der erfindungsgemäßen Substanzen liegt bei 0,5 bis 300 mg, vorzugsweise 1 bis IiO mg (oral) bzw. 0,1 bis 10 mg (parenteral).The single dose of the substances according to the invention is 0.5 to 300 mg, preferably 1 to 10 mg (orally) or 0.1 to 10 mg (parenteral).

2i) Die überlegene Wirkung der erfindungsgemäßen Verbindungen gegenüber aus DT-AS 15 43 357 und 16 43 237 bekannten strukturähnlichen Derivaten ist der Tabelle I zu entnehmen.2i) The superior action of the compounds according to the invention compared to DT-AS 15 43 357 and 16 43 237 known structurally similar derivatives can be found in Table I.

Verbindung (als HCl-Saiz)Compound (as HCl Saiz)

lsoproterenol-isoproterenol-

anüigonistischermore anuigonistic

Effekt*)Effect*)

A. Stand der TechnikA. State of the art

l-(2-Nitrilo-3-methylphenoxy)-2-hydroxy-3-isopropylaminopropan 55fach DCI1- (2-Nitrilo-3-methylphenoxy) -2-hydroxy-3-isopropylaminopropane 55-fold DCI

l-(2-Nitrilo-3-methylphenoxy)-2-hydroxy-t-butylaminopropan 60fach DCI1- (2-Nitrilo-3-methylphenoxy) -2-hydroxy-t-butylaminopropane 60X DCI

l-(2-Nitrilo-3-methylphenoxy)-2-hydroxy-3-s-butylaminopropan 14fach DCI1- (2-Nitrilo-3-methylphenoxy) -2-hydroxy-3-s-butylaminopropane 14X DCI

l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-3-isopropylarninopropan 43fach DCI1- (2-Nitrilo-5-methylphenoxy) -2-hydroxy-3-isopropyl aminopropane 43-fold DCI

B. ErfindungsgemäßB. According to the invention

l-(2-Nitrilo-5-methyIphenoxy)-2-hydroxy-3-s-butylaminopropan 74fach DCI1- (2-Nitrilo-5-methylphenoxy) -2-hydroxy-3-s-butylaminopropane 74-fold DCI

l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-t-butylaminopropan 777fach DCI1- (2-Nitrilo-5-methylphenoxy) -2-hydroxy-t-butylaminopropane 777-fold DCI

l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-3-(l,l-dimethyl-n-propylamino)-propan 130fach DCI1- (2-Nitrilo-5-methylphenoxy) -2-hydroxy-3- (1,1-dimethyl-n-propylamino) propane 130-fold DCI

l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-3-(l,I-dimethyl-n-butylamino)-propan 47fach DCI1- (2-Nitrilo-5-methylphenoxy) -2-hydroxy-3- (1,1-dimethyl-n-butylamino) propane 47-fold DCI

*) Die Tests wurden an lebenden Meerschweinchen durchgeführt. Als Standardsubstanz diente 3,4-Dichiorisoproterenol (DCI), dessen Wirkung gleich 1 gesetzt wurde.*) The tests were carried out on live guinea pigs. 3,4-dichiorisoproterenol was used as the standard substance (DCI), the effect of which was set equal to 1.

Die galenische Verarbeitung der erfindungsgemäßen Verbindungen bzw. ihrer Säureadditionssalze zu den üblichen Anwendungsformen wie Lösungen, Emulsionen, Tabletten, Dragees oder Depotformen kann in bekannter Weise unter Heranziehung der dafür gebräuchlichen galenischen Hilfs-, Träger-, Spreng-, Binde-, Überzugs- oder Schmiermittel, Geschmacksstoffe, Süßungsmittel, Mittel zur Erzielung eines Depoteffekts oder Lösungsvermittler geschehen.The pharmaceutical processing of the invention Compounds or their acid addition salts for the usual application forms such as solutions, emulsions, Tablets, coated tablets or depot forms can be used in a known manner using the for this Common pharmaceutical auxiliaries, carriers, disintegrants, binders, coatings or lubricants, flavorings, sweeteners, agents for achieving one Depot effect or solubilizer happen.

Die folgenden Beispiele erläutern die Erfindung näher:The following examples explain the invention in more detail:

A. VerfahrensbeispieleA. Process examples Beispiel 1example 1

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-sek.-butylaminopropan-hydrochlorid 1- (2-cyano-5-methylphenoxy) -2-hydroxy-3-sec-butylaminopropane hydrochloride

Aus 6,5 g (0,02MoI) l-(2-Amino-5-methyI-phenoxy)-2-hydoxy-3-sek.-butylaminopropam-dihydrochlorid, 10 ml konz. HCl und 40 ml HA 2,8 g (0,04 Mol) NaNO2 und 10 ml H2O wird eine Diazonium-Salzlösung hergestellt. Diese wird in eine 90° C heiße Lösung aus 10 g Kupfersulfat, 11,2g Kaliumcyanid und 60 ml H2O eingerührt und 30 Minuten bei 85 bis 90° C belassen. Nach Abkühlen wird alkalisch gemacht, ausfallende verharzte Anteile werden abgetrennt Nach Extraktion mit CHCl3 wird die CHCl3-Lösung über MgSO4 getrocknet, dann das CHCl3 abdestilliert. Der Rückstand wird durch Säulenchromatographie (z. B.From 6.5 g (0.02MoI) 1- (2-amino-5-methyI-phenoxy) -2-hydoxy-3-sec-butylaminopropam dihydrochloride, 10 ml conc. HCl and 40 ml HA 2.8 g (0.04 mol) NaNO 2 and 10 ml H 2 O a diazonium salt solution is prepared. This is stirred into a 90 ° C. solution of 10 g of copper sulfate, 11.2 g of potassium cyanide and 60 ml of H 2 O and left at 85 to 90 ° C. for 30 minutes. After cooling, the mixture is made alkaline, resinous components which precipitate are separated off. After extraction with CHCl 3 , the CHCl 3 solution is dried over MgSO 4 , then the CHCl 3 is distilled off. The residue is purified by column chromatography (e.g.

Kieselgel) gereinigt. Nach Eindampfen der Fraktionen mit einheitlicher Substanz wird die verbleibende Base in wenig Äther gelöst und mit ätherischer HCl angesäuert. Das ausfallende Hydrochlorid wird aus Äthanol unter Zugabe von Äther umkristallisiert.Silica gel). After evaporation of the fractions with uniform substance, the remaining base is in Dissolved a little ether and acidified with ethereal HCl. The precipitating hydrochloride is taken from ethanol Addition of ether recrystallized.

Ausbeute: 1,8g;F = 113bisll5°C.Yield: 1.8g, m.p. 113 to 115 ° C. Beispiel 2Example 2

l-(2-Cyano-5-n\ethylphenoxy)-2-hydroxy-3-tert.-butyl aminopropan-hydrochlorid1- (2-cyano-5-n-ethylphenoxy) -2-hydroxy-3-tert-butyl aminopropane hydrochloride

9,75 g (0,03 Mol) l-(2-Amino-5-methylphenoxy)-2-hydroxy-3-tert.-butylaminopropan-dihydrochlorid werden in 15 ml konz. HCl und 60 ml H2O mit 4,2 g (0,06 Mol)9.75 g (0.03 mol) of 1- (2-amino-5-methylphenoxy) -2-hydroxy-3-tert-butylaminopropane dihydrochloride are concentrated in 15 ml. HCl and 60 ml H 2 O with 4.2 g (0.06 mol)

NaNO2 in 15 ml H2O bei 0 bis 5°C diazotiert Die Diazoniumsalzlösung wird in eine auf 90° C erhitzte Lösung aus 15 g Kupfersulfat, 16,8 g KCN und 90 ml H2O eingerührt und 30 Minuten bei 85 bis 9O0C nachgerührt. Nach Abkühlen wird mit NaOH alkalisch gestellt. Das Ganze wird mit CHCl3 extrahiert, verharzte Anteile und die wäßrige Phase werden abgetrennt Nach Waschen der organischen Phase mit H2O wird über MgSO4 getrocknet. Das CHCb wird abdestilliert, wobei 6,8 g Rohsubstanz verbleiben. Sie wird aus Äthanol unter Zugabe von Äther umkristallisiert. NaNO 2 diazotized in 15 ml H 2 O at 0 to 5 ° C. The diazonium salt solution is stirred into a heated to 90 ° C solution of 15 g copper sulfate, 16.8 g KCN and 90 ml H 2 O and 30 minutes at 85 to 90 0 C. After cooling, it is made alkaline with NaOH. The whole is extracted with CHCl 3 , resinified portions and the aqueous phase are separated off. After washing the organic phase with H 2 O, it is dried over MgSO 4. The CHCb is distilled off, with 6.8 g of crude substance remaining. It is recrystallized from ethanol with the addition of ether.

Ausbeute: 4,9 g. Nach Überführung in das Hydrochlorid analog dem vorhergehenden Beispiel liegt der Festpunkt bei 231 bis 232° C.Yield: 4.9 g. After conversion into the hydrochloride analogously to the previous example, the fixed point is at 231 to 232 ° C.

Beispiel 3Example 3

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-(l,l-dimethyl-propylamino)-propan-liydrochlorid 1- (2-Cyano-5-methylphenoxy) -2-hydroxy-3- (1,1-dimethyl-propylamino) -propane hydrochloride

Aus 10,2 g (0,03MoI) l-(2-Amino-5-methylphenoxy)-2-hydroxy-3-(l,l-dimethylpropylarnino)-propan-dihydrochlorid, 15 ml konz. HCI und 60 ml H2O und 4,2 g (0,06 Mol) NaNO2 in 15 ml H2O wird eine Diazoniumlösung hergestellt Diese wird in eine heiße Lösung aus 15 g Kupfersulfat, 16,8 g KCN und 90 ml H2O eingerührt und 30 Minuten bei ca. 90° C gehalten. Nach Abkühlen wird alkalisch gemacht und mit CHCI3 ausgeschüttelt. Unlösliche Anteile und die wäßrige Phase werden abgetrennt. Nach Trocknen der CHC13-Lösung über MgSO4 wird das CHCl3 abdestilliert und der Rückstand über eine Kieselgelsäule gereinigt. Nach Vereinigung der die Substanz enthaltenden Fraktionen wird das Lösungsmittelgemisch abdestilliert und die reine Base in Äther gelöst. Durch Zugabe von ätherischer HCl fällt das Hydrochlorid kristallin aus. Es wird aus Äthanol unter Zugabe von Äther umkristallisiert. Ausbeute: 2,2 g; F = 187 bis 188°C.From 10.2 g (0.03 mol) 1- (2-amino-5-methylphenoxy) -2-hydroxy-3- (l, l-dimethylpropylarnino) propane dihydrochloride, 15 ml conc. HCl and 60 ml of H 2 O and 4.2 g (0.06 mol) of NaNO 2 in 15 ml of H 2 O, a diazonium solution is prepared 2 O stirred in and held at approx. 90 ° C. for 30 minutes. After cooling, it is made alkaline and extracted with CHCl3. Insoluble fractions and the aqueous phase are separated off. After the CHCl 3 solution has been dried over MgSO 4 , the CHCl 3 is distilled off and the residue is purified on a silica gel column. After the fractions containing the substance have been combined, the solvent mixture is distilled off and the pure base is dissolved in ether. The hydrochloride precipitates in crystalline form by adding ethereal HCl. It is recrystallized from ethanol with the addition of ether. Yield: 2.2 g; F = 187 to 188 ° C.

B. FormulierungsbeispieleB. Formulation Examples

1. Tabletten
Die Tabletten werden aus folgenden Bestandteilen1. Tablets
The tablets are made up of the following ingredients

hergestellt:manufactured:

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-tert-butyIaminopropan-hydrochIorid Maisstärke
Calciumphosphat
Magnesiumstearat1- (2-Cyano-5-methylphenoxy) -2-hydroxy-3-tert-butylaminopropane hydrochloride corn starch
Calcium phosphate
Magnesium stearate

Beispiel 4Example 4

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-äthylaminopropanhydrochlorid 1- (2-cyano-5-methylphenoxy) -2-hydroxy-3-ethylaminopropane hydrochloride

7,45 g (0,0395 Mol) l-(2-Cyano-5-methylphenoxy)-2,3-epoxypropan werden in 60 ml Äthanol gelöst, 9 g (0,2 Mol) Äthylamin zugegeben und unter Rückfluß zwei Stunden zum Sieden erhitzt. Nach Abkühlung wird das Lösungsmittel im Vakuum abdestilliert, der Rückstand mit verd. HCl angesäuert und unlösliche Anteile abfiltriert Das Filtrat wird mit NaOH alkalisch gestellt, wobei die freiwerdende Base kristallin ausfällt. Sie wird isoliert, getrocknet und aus Essigester unter Zugabe von Petroläther umkristallisiert Das Kristallisat wird sodann in etwas Acetonitril gelöst, ätherische HCl zugegeben und das ausfallende Hydrochlorid abgesaugt. Ausbeute: 4,5 g; F = 160 bis 1620C.7.45 g (0.0395 mol) of 1- (2-cyano-5-methylphenoxy) -2,3-epoxypropane are dissolved in 60 ml of ethanol, 9 g (0.2 mol) of ethylamine are added and the mixture is refluxed for two hours Boiling heated. After cooling, the solvent is distilled off in vacuo, the residue is acidified with dilute HCl and insoluble fractions are filtered off. The filtrate is made alkaline with NaOH, the base released precipitating in crystalline form. It is isolated, dried and recrystallized from ethyl acetate with the addition of petroleum ether. The crystals are then dissolved in a little acetonitrile, ethereal HCl is added and the hydrochloride which precipitates is filtered off with suction. Yield: 4.5 g; F = 160 to 162 0 C.

Beispiel 5Example 5

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-(l,l-dimethylbutylamino)-propan-hydrochlorid 1- (2-cyano-5-methylphenoxy) -2-hydroxy-3- (l, l-dimethylbutylamino) propane hydrochloride

7,45 g (0,0395 Mol) l-(2-Cyano-5-methylphenoxy)-2,3-epoxypropan werden in 60 ml Äthanol gelöst, 15 ml (0,0825 Mol) 1,1-Dimethylbutylamin zugegeben und wie in Beispiel 4 umgesetzt und aufgearbeitet. Ausbeute: 5,7 g;F = 180 bis 1830C. 20,0 g 164,0 g 240,0 g 1.0 g7.45 g (0.0395 mol) of 1- (2-cyano-5-methylphenoxy) -2,3-epoxypropane are dissolved in 60 ml of ethanol, 15 ml (0.0825 mol) of 1,1-dimethylbutylamine are added and how implemented in Example 4 and worked up. Yield: 5.7 g; F = 180-183 0 C. 20.0 g 164.0 g 240.0 g 1.0 g

425,0 g425.0 g

Die einzelnen Bestandteile werden intensiv miteinan-The individual components are intensively

der vermischt und die Mischung in üblicher Weise granuliert Das Granulat wird sodann zu 1000 Tabletten von 425 mg Gewicht verpreßt, von denen jede 20 mgwhich is mixed and the mixture is granulated in the usual way. The granulate is then made into 1000 tablets of 425 mg weight, each of which 20 mg

Wirkstoff enthält.Contains active ingredient.

2. Gelatine-Kapseln2. Gelatin capsules

Der Inhalt der Kapseln setzt sich wie folgt zusammen:The contents of the capsules are made up as follows:

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-l- (2-cyano-5-methylphenoxy) -2-hydroxy-

3-tert-butylaminopropan-maIeinat 25,0 mg3-tert-butylaminopropane malate 25.0 mg

Maisstärke 175,0 mgCorn starch 175.0 mg

200,0 mg200.0 mg

Die Bestandteile des Kapselinhaits werden intensiv vermischt, und 200-mg-Portionen der Mischung werden Jd in Gelatine-Kapseln geeigneter Größe abgefüllt. Jede Kapsel enthält 25 mg des Wirkstoffs.The ingredients of the capsule contents are mixed intensively, and 200 mg servings of the mixture are made Jd filled in gelatin capsules of suitable size. Every Capsule contains 25 mg of the active ingredient.

3. Injektionslösung3. Solution for injection

Die Lösung wird aus folgenden Bestandteilen Jj hergestellt:The solution is made up of the following components Jj:

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-l- (2-cyano-5-methylphenoxy) -2-hydroxy-

3-tert-butylaminopropan-hydrochlorid 1,5 Teile Natriumsalz der Äthylendiamintetra-3-tert-butylaminopropane hydrochloride 1.5 parts Sodium salt of ethylenediaminetetra-

essigsäure 0,2 Teileacetic acid 0.2 parts

4(1 dest Wasser, ad 100,0 Teile 4 (1 distilled water, ad 100.0 parts

Der Wirkstoff und das Salz der Äthyiendiamintetraessigsäure werden in genügend Wasser gelöst und mit Wasser auf das gewünschte Volumen aufgefüllt Die ■Γ) Lösung wird von suspendierten Partikeln abfiltriert und in 1 cm3-Ampullen unter aseptischen Bedingungen abgefüllt Zuletzt werden die Ampullen sterilisiert und verschlossen. Jede Ampulle enthält 15 mg Wirkstoff.The active ingredient and the salt of ethylenediaminetetraacetic acid are dissolved in sufficient water and made up to the desired volume with water. The solution is filtered off from suspended particles and filled into 1 cm 3 ampoules under aseptic conditions. Finally, the ampoules are sterilized and sealed. Each ampoule contains 15 mg of active ingredient.

4. Depotdragees4. Depot dragees

Der Kern setzt sich wie folgt zusammen:The core is composed as follows:

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-S-selc-butylaminopropan-hydrochlorid Carbocymethylcelluiose
Stearinsäure
Celluloseacetatphthalat1- (2-cyano-5-methylphenoxy) -2-hydroxy-S-selc-butylaminopropane hydrochloride carbocymethyl cellulose
Stearic acid
Cellulose acetate phthalate

45,0 g 295,0 g 20,0 g 40,0 g45.0 g 295.0 g 20.0 g 40.0 g

400,0 g400.0 g

bo Der Wirkstoff, die Carboxymethylcellulose und die Stearinsäure werden intensiv gemischt und die Mischung in üblicher Weise granuliert, wobei man eine Lösung des ceiiuloseacetatphthalats in 200 ml eines Gemisches aus Äthanol/Äthylacetat verwendet Dasbo The active ingredient, the carboxymethyl cellulose and the Stearic acid are mixed intensively and the mixture is granulated in the usual way, whereby one Solution of ceiiuloseacetatphthalats in 200 ml of a mixture of ethanol / ethyl acetate used

fa5 Granulat wird dann zu 400-mg-Kernen verpreßt, die in üblicher Weise mit einer zuckerhaltigen 5%igen Lösung von Polyvinylpyrrolidon in Wasser überzogen werden. Jedes Drag6e enthält 25 mg Wirkstoff.fa5 granules are then compressed into 400 mg cores, which are packed into Usually coated with a sugar-containing 5% solution of polyvinylpyrrolidone in water. Each Drag6e contains 25 mg of active ingredient.

Claims (3)

Patentansprüche:Patent claims: 1. 1 -(2-Cyano-5-methylphenoxy)-2-hydroxy-3-alkylaminopropane der Formel (I)1. 1 - (2-Cyano-5-methylphenoxy) -2-hydroxy-3-alkylaminopropanes of formula (I) -CH2-CHOH-CH2-NHR (I)-CH 2 -CHOH-CH 2 -NHR (I) in der R eine Äthylgruppe oder eine Alkylgruppe mit 4 bis 6 C-Atomen bedeutet, sowie deren physiologisch verträgliche Säureadditionssalze.in which R is an ethyl group or an alkyl group with 4 to 6 carbon atoms, as well as their physiological compatible acid addition salts. 2. 1 -^-Cyano-S-methylphenoxy^-hydroxy-S-tert.-butylaminopropan sowie seine physiologisch verträglichen Säureadditionssalze.2.1 - ^ - Cyano-S-methylphenoxy ^ -hydroxy-S-tert-butylaminopropane as well as its physiologically compatible acid addition salts. 3. Verfahren zur Herstellung von l-(2-Cyano-5-methyIphenoxy)-2-hydroxy-3-aikylaminopropanen der Formel I und deren Säureadditionssalzen nach Anspruch 1, dadurch gekennzeichnet, daß man in an sich bekannter Weise
a) eine Verbindung der Formel (H)3. A process for the preparation of l- (2-cyano-5-methyIphenoxy) -2-hydroxy-3-aikylaminopropanes of the formula I and their acid addition salts according to Claim 1, characterized in that one is carried out in a manner known per se
a) a compound of the formula (H)
DE19691950351 1969-08-05 1969-10-06 1- (2-Cyano-5-methylphenoxy) -2-hydroxy-3-aIkylaminopropane, process for their preparation and medicaments containing them Expired DE1950351C3 (en)

Priority Applications (65)

Application Number Priority Date Filing Date Title
BG018263A BG17528A3 (en) 1969-10-06 1969-10-02 METHOD FOR OBTAINING SUBSTITUTED ALKYLAMINOPROPANES
DE19691950351 DE1950351C3 (en) 1969-10-06 1969-10-06 1- (2-Cyano-5-methylphenoxy) -2-hydroxy-3-aIkylaminopropane, process for their preparation and medicaments containing them
BG015085A BG17590A3 (en) 1969-08-05 1970-07-02 METHOD FOR OBTAINING NEW PYRIMIDINE DERIVATIVES
CS646770A CS162731B2 (en) 1969-10-06 1970-09-23
BG018262A BG17294A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING NEW 1-<2-CYANO-5-METHYLPHENOXY>-2-HYDROXY-3-ALKYLAMINOPROPANES
CH546221D CH546221A (en) 1969-10-06 1970-10-02 PROCESS FOR THE PREPARATION OF NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-ALKYLAMINOPROPANES.
CH697273A CH553166A (en) 1969-10-06 1970-10-02 PROCESS FOR THE PREPARATION OF NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-ALKYLAMINOPROPANES.
BG018264A BG17295A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING SUBSTITUTED ALKYLAMINOPROPANES
CH697773A CH553167A (en) 1969-10-06 1970-10-02 METHOD OF PREPARING NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-SEC.-ALKYLAMINOPROPANES.
CH697573A CH542815A (en) 1969-10-06 1970-10-02 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
CH546218D CH546218A (en) 1969-10-06 1970-10-02 PROCESS FOR THE PREPARATION OF NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-ALKYLAMINOPROPANES.
BG018268A BG17531A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING ALKYLAMINOPROPANES
CH1461770A CH542814A (en) 1969-10-06 1970-10-02 Process for the preparation of new 1- (2'-cyano-5'-methyl-phenoxy) -2-hydroxy-3-alkylaminopropanes
BG018266A BG17529A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING ALKYLAMINOPROPANES
BG018261A BG17527A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING SUBSTITUTED ALKYLAMINOPROPOLS
BG015776A BG17293A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING SUBSTITUTED ALKYLAMINOPROPANE
BG018265A BG17296A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING SUBSTITUTED ALKYLAMINOPROPANES
CH546222D CH546222A (en) 1969-10-06 1970-10-02 PROCESS FOR THE PREPARATION OF NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-ALKYLAMINOPROPANES.
CH546219D CH546219A (en) 1969-10-06 1970-10-02 PROCESS FOR THE PREPARATION OF NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-ALKYLAMINOPROPANES.
CH696973A CH555322A (en) 1969-10-06 1970-10-02 PROCESS FOR THE PREPARATION OF NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-ALKYLAMINOPROPANES.
CH546220D CH546220A (en) 1969-10-06 1970-10-02 PROCESS FOR THE PREPARATION OF NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-ALKYLAMINOPROPANES.
ES384244A ES384244A1 (en) 1969-10-06 1970-10-03 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
SU1705074A SU400081A1 (en) 1970-10-05 METHOD OF OBTAINING OPTICALLY ACTIVE
SU1481523A SU361563A1 (en) 1970-10-05 METHOD OF OBTAINING 1-
SU1705732A SU423291A3 (en) 1969-10-06 1970-10-05
SU1705733A SU421182A3 (en) 1969-10-06 1970-10-05 METHOD OF OBTAINING 1-
SE1347570A SE375094B (en) 1969-10-06 1970-10-05
SU1705040A SU400082A1 (en) 1970-10-05 In PTB
SU1705730A SU417938A3 (en) 1969-10-06 1970-10-05 METHOD OF OBTAINING 1-
PL17334370A PL84637B1 (en) 1969-10-06 1970-10-05 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia [DE1950351A1]
PL14378570A PL84252B1 (en) 1969-10-06 1970-10-05 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia [DE1950351A1]
PL17334270A PL84642B1 (en) 1969-10-06 1970-10-05 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia [DE1950351A1]
DK505570A DK128237B (en) 1969-10-06 1970-10-05 Analogous process for the preparation of racemic or optically active N-alkyl-substituted (2-cyano-5-methylphenoxy) -propanolamines or physiologically acceptable acid addition salts thereof.
JP8675670A JPS501262B1 (en) 1969-10-06 1970-10-05
SU1699774A SU426360A3 (en) 1969-10-06 1970-10-05 METHOD OF OBTAINING 1-
SU1705731A SU422137A3 (en) 1969-10-06 1970-10-05 METHOD OF OBTAINING 1-
YU244470A YU34516B (en) 1969-10-06 1970-10-05 Process for preparing novel 1-(2-cyano-5-methylphenoxy)-2-hydroxy-3-alkylamino propanes
AT900970A AT302274B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkylaminopropanes and their acid addition salts
AT1052371A AT308072B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkylaminopropanes and of their acid addition salts
RO6726970A RO59185A (en) 1969-10-06 1970-10-06
RO6728970A RO58550A (en) 1969-10-06 1970-10-06
RO6727070A RO58533A (en) 1969-10-06 1970-10-06
RO6726870A RO58532A (en) 1969-10-06 1970-10-06
RO6727170A RO59186A (en) 1969-10-06 1970-10-06
AT1053071A AT306700B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkylaminopropanes, as well as their acid addition salts
AT1052671A AT306696B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkylaminopropanes, as well as their acid addition salts
AT1052571A AT306695B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkyl-aminopropanes, as well as their acid addition salts
AT1052971A AT306699B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkylaminopropanes, as well as their acid addition salts
RO6727270A RO58534A (en) 1969-10-06 1970-10-06
RO6461670A RO56983A (en) 1969-10-06 1970-10-06
RO6727370A RO58548A (en) 1969-10-06 1970-10-06
AT1052771A AT306697B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkylaminopropanes, as well as their acid addition salts
RO6727470A RO58549A (en) 1969-10-06 1970-10-06
AT1052471A AT306694B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkyl-aminopropanes, as well as their acid addition salts
AT1052871A AT306698B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-alkylaminopropanes, as well as their acid addition salts
AT1053171A AT306701B (en) 1969-10-06 1970-10-06 Process for the preparation of new racemic or optically active 1- (2'-cyano-5'-methylphenoxy) -2-hydroxy-3-sec. alkylaminopropanes, as well as their acid addition salts
ES391141A ES391141A1 (en) 1969-10-06 1971-05-13 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
ES391139A ES391139A1 (en) 1969-10-06 1971-05-13 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
ES391136A ES391136A1 (en) 1969-10-06 1971-05-13 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
ES391135A ES391135A1 (en) 1969-10-06 1971-05-13 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
ES391140A ES391140A1 (en) 1969-10-06 1971-05-13 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
ES391137A ES391137A1 (en) 1969-10-06 1971-05-13 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
ES391138A ES391138A1 (en) 1969-10-06 1971-05-13 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
ES391134A ES391134A1 (en) 1969-10-06 1971-05-13 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
SU1699773A SU503507A3 (en) 1969-10-06 1971-09-21 The method of obtaining 1- (2-cyano-5-methylphenoxy) -2-hydroxy-3-alkylaminopropane

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19691950351 DE1950351C3 (en) 1969-10-06 1969-10-06 1- (2-Cyano-5-methylphenoxy) -2-hydroxy-3-aIkylaminopropane, process for their preparation and medicaments containing them

Publications (3)

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DE1950351A1 DE1950351A1 (en) 1971-04-29
DE1950351B2 true DE1950351B2 (en) 1978-04-27
DE1950351C3 DE1950351C3 (en) 1978-12-21

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Country Status (13)

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JP (1) JPS501262B1 (en)
AT (10) AT306696B (en)
BG (8) BG17528A3 (en)
CH (1) CH542814A (en)
CS (1) CS162731B2 (en)
DE (1) DE1950351C3 (en)
DK (1) DK128237B (en)
ES (9) ES384244A1 (en)
PL (3) PL84252B1 (en)
RO (9) RO58533A (en)
SE (1) SE375094B (en)
SU (6) SU423291A3 (en)
YU (1) YU34516B (en)

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AT306697B (en) 1973-04-25
SU503507A3 (en) 1976-02-15
PL84642B1 (en) 1976-04-30
AT306698B (en) 1973-04-25
SU417938A3 (en) 1974-02-28
AT306699B (en) 1973-04-25
DE1950351A1 (en) 1971-04-29
SU421182A3 (en) 1974-03-25
PL84252B1 (en) 1976-03-31
AT306694B (en) 1973-04-25
SU422137A3 (en) 1974-03-30
BG17293A3 (en) 1973-07-25
SU426360A3 (en) 1974-04-30
BG17527A3 (en) 1973-11-10
BG17294A3 (en) 1973-07-25
SU400081A3 (en) 1973-10-03
ES391139A1 (en) 1973-07-16
ES391134A1 (en) 1973-07-16
DE1950351C3 (en) 1978-12-21
YU34516B (en) 1979-09-10
AT306696B (en) 1973-04-25
JPS501262B1 (en) 1975-01-16
ES391137A1 (en) 1973-07-16
AT308072B (en) 1973-06-25
BG17529A3 (en) 1973-11-10
ES391135A1 (en) 1973-07-16
RO58533A (en) 1975-08-15
DK128237B (en) 1974-03-25
RO58550A (en) 1975-08-15
SE375094B (en) 1975-04-07
RO58532A (en) 1975-09-15
YU244470A (en) 1979-02-28
ES391141A1 (en) 1973-07-16
ES384244A1 (en) 1973-01-01
RO58549A (en) 1975-08-15
PL84637B1 (en) 1976-04-30
BG17528A3 (en) 1973-11-10
ES391136A1 (en) 1973-07-16
BG17296A3 (en) 1973-07-25
ES391138A1 (en) 1973-07-16
ES391140A1 (en) 1973-07-16
AT306700B (en) 1973-04-25
AT306695B (en) 1973-04-25
AT302274B (en) 1972-10-10
SU361563A3 (en) 1972-12-07
RO58548A (en) 1975-09-15
CS162731B2 (en) 1975-07-15
BG17531A3 (en) 1973-11-10
SU423291A3 (en) 1974-04-05
RO58534A (en) 1975-09-15
AT306701B (en) 1973-04-25
RO59186A (en) 1976-01-15
BG17295A3 (en) 1973-07-25
RO59185A (en) 1976-01-15
SU400082A3 (en) 1973-10-03
RO56983A (en) 1974-12-15
CH542814A (en) 1973-10-15

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