Nothing Special   »   [go: up one dir, main page]

DE1950351C3 - 1- (2-Cyano-5-methylphenoxy) -2-hydroxy-3-aIkylaminopropane, process for their preparation and medicaments containing them - Google Patents

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

Info

Publication number
DE1950351C3
DE1950351C3 DE19691950351 DE1950351A DE1950351C3 DE 1950351 C3 DE1950351 C3 DE 1950351C3 DE 19691950351 DE19691950351 DE 19691950351 DE 1950351 A DE1950351 A DE 1950351A DE 1950351 C3 DE1950351 C3 DE 1950351C3
Authority
DE
Germany
Prior art keywords
methylphenoxy
hydroxy
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.)
Expired
Application number
DE19691950351
Other languages
German (de)
Other versions
DE1950351B2 (en
DE1950351A1 (en
Inventor
A Engelhardt
H Koppe
K Zeile
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.)
CH Boehringer Sohn AG and Co KG
Original Assignee
CH Boehringer Sohn AG and Co KG
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
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 BG015776A priority patent/BG17293A3/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 BG018262A priority patent/BG17294A3/en
Priority to BG018264A priority patent/BG17295A3/en
Priority to CH697573A priority patent/CH542815A/en
Priority to CH546218D priority patent/CH546218A/en
Priority to CH697773A priority patent/CH553167A/en
Priority to CH546221D priority patent/CH546221A/en
Priority to BG018265A priority patent/BG17296A3/en
Priority to CH546220D priority patent/CH546220A/en
Priority to CH546219D priority patent/CH546219A/en
Priority to CH696973A priority patent/CH555322A/en
Priority to CH546222D priority patent/CH546222A/en
Priority to CH697273A priority patent/CH553166A/en
Priority to ES384244A priority patent/ES384244A1/en
Priority to SU1705732A priority patent/SU423291A3/ru
Priority to DK505570A priority patent/DK128237B/en
Priority to SU1481523A priority patent/SU361563A1/en
Priority to SU1705074A priority patent/SU400081A1/en
Priority to PL17334270A priority patent/PL84642B1/en
Priority to SU1705733A priority patent/SU421182A3/en
Priority to PL17334370A priority patent/PL84637B1/en
Priority to JP8675670A priority patent/JPS501262B1/ja
Priority to SU1705730A priority patent/SU417938A3/en
Priority to YU244470A priority patent/YU34516B/en
Priority to SE1347570A priority patent/SE375094B/xx
Priority to PL14378570A priority patent/PL84252B1/en
Priority to SU1705040A priority patent/SU400082A1/en
Priority to SU1705731A priority patent/SU422137A3/en
Priority to SU1699774A priority patent/SU426360A3/en
Priority to RO6726970A priority patent/RO59185A/ro
Priority to AT1052971A priority patent/AT306699B/en
Priority to AT1052871A priority patent/AT306698B/en
Priority to AT1053171A priority patent/AT306701B/en
Priority to AT1053071A priority patent/AT306700B/en
Priority to RO6728970A priority patent/RO58550A/ro
Priority to RO6727270A priority patent/RO58534A/ro
Priority to RO6727470A priority patent/RO58549A/ro
Priority to AT1052371A priority patent/AT308072B/en
Priority to RO6727070A priority patent/RO58533A/ro
Priority to AT1052571A priority patent/AT306695B/en
Priority to AT900970A priority patent/AT302274B/en
Priority to RO6726870A priority patent/RO58532A/ro
Priority to RO6727370A priority patent/RO58548A/ro
Priority to RO6461670A priority patent/RO56983A/ro
Priority to AT1052471A priority patent/AT306694B/en
Priority to AT1052671A priority patent/AT306696B/en
Priority to RO6727170A priority patent/RO59186A/ro
Priority to AT1052771A priority patent/AT306697B/en
Publication of DE1950351A1 publication Critical patent/DE1950351A1/en
Priority to ES391141A priority patent/ES391141A1/en
Priority to ES391136A priority patent/ES391136A1/en
Priority to ES391134A priority patent/ES391134A1/en
Priority to ES391139A priority patent/ES391139A1/en
Priority to ES391140A priority patent/ES391140A1/en
Priority to ES391135A priority patent/ES391135A1/en
Priority to ES391138A priority patent/ES391138A1/en
Priority to ES391137A priority patent/ES391137A1/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

Links

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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Mechanical Engineering (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (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

Q-CH2-ZQ-CH 2 -Z

(H)(H)

CH3 worin Z die GruppeCH 3 wherein Z is the group

-CH- \-CH- \

CH2 CH 2

NH2-RNH 2 -R

(III)(III)

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)

NH2 NH 2

O-CH2-CHOH-CH2-NHRO-CH 2 -CHOH-CH 2 -NHR

CH,CH,

(IV)(IV)

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

Die erfindungsgemäßen Verbindungen entsprechen der Formel (1)The compounds according to the invention correspond to the formula (1)

CH3 CH 3

in der R eine Äthylgruppe oder eine Alkylgruppe mit 4 bis 6 C-Atomen bedeutet, sowie deren physiologisch verträgliche Säureadditionssalze.in which R denotes an ethyl group or an alkyl group with 4 to 6 carbon atoms, as well as their physiologically acceptable acid addition salts.

2. 1 -(2-Cyano-5-methylphenoxy)-2-hydroxy-3-tert-butylaminopropan sowie seine physiologisch verträglichen Säureadditionssalze.2. 1 - (2-cyano-5-methylphenoxy) -2-hydroxy-3-tert-butylaminopropane as well as its physiological compatible acid addition salts.

3. Verfahren zur Herstellung vor. l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-aJkylaminopropanen3. Method of manufacture before. 1- (2-cyano-5-methylphenoxy) -2-hydroxy-3-alkylaminopropanes der Formel I und deren Säureadditionssalzen nach Anspruch 1, dadurch gekennzeichnet, daß man in an sich bekannter Weise a) eine Verbindung der Formel (II)of the formula I and their acid addition salts according to Claim 1, characterized in that in an known way a) a compound of the formula (II)

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)

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

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

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),

Q-CH2-ZQ-CH 2 -Z

(H)(H)

CH3 worin Z die GruppeCH 3 wherein 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)

NH2-RNH 2 -R

(III)(III)

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

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

worin R die oben angegebene Bedeutung hat.wherein R has the meaning given above.

Das für die Durchführung der Verfahren benötigte Ausgangsmatenal 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 Il 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)-23-epoxypropan läßt sich durch Umsetzung mit den entsprechenden Halogenwasserstoffsäuren in die HaIogenhydrine der Formel Il überführen.The starting material required to carry out the procedure is partly already known, partly it can be obtained by conventional methods. For example, the l- (2-cyano-5-methylphenoxy) -2,3-epoxypropane of the formula II can easily be converted into Represent epichlorohydrin with 2-cyano-5-methylphenol or one of its salts in an alkaline medium. The l- (2-cyano-5-methylphenoxy) -23-epoxypropane obtained in this way can be reacted with the convert the corresponding hydrohalic acids into the halohydrins of the formula II.

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

beschriebenen Verfahren a), ausgehend von dem entsprechenden substituierten Phenol Ober das entsprechende l-Phenoxy-2^-epoxypropan durch Umsetzung des letzteren mit einem Alkylaroin 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 over the corresponding l-phenoxy-2 ^ -epoxypropane by reaction the latter with an alkylaroin of 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 Racematentrennung mit üblichen Hilfssäuren, wie Dibenzoyl-D-weinsäure, Ditoluyl-D-weinsäure oder D-3-Bromcampher-8-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 Racemate resolution with customary auxiliary acids such as dibenzoyl-D-tartaric acid, ditoluyl-D-tartaric acid or D-3-bromocamphor-8-sulfonic acid, also by onset from optically active starting material.

Die erfindungsgemäßen Substanzen der Formel I können in üblicher Weise in ihre physiologisch verträglichen Säurtadditionssalze überführt werden. Geeignete Säuren sind beispielsweise Salzsäure, Brom· wasserstoffsäure, 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, bromine hydrochloric acid, sulfuric acid, methanesulfonic acid, maleic acid, acetic acid, oxalic acid, lactic acid, tartaric acid, succinic acid or 8-chlorotheophylline.

Tabelle ITable I.

1010

1515th

2020th Die Verbindungen der Formel I bzw. deren physiologisch verträgliche Säureadditionssalze haben im Tierversuch an Meerschweinchen hervorragende therapeutische, insbesondere /?-adreno!ytische Eigenschaften gezeigt und können daher beispielsweise zur Behandlung oder Prophylaxe von Erkrankungen der Herzkranzgsfäße und zur Behandlung von Herzarrhythmien, insbesondere Tachycardien, in der Humanmedizin eingesetzt werden. Sie sind dabei strukturähnlichen bekannten Verbindungen, wie beispielsweise dem l-(2-Cyano-3-methylphenoxy)-2-hydroxy-3-isopropylaminopropan und dem l-(2-Cyano-3-methyIphenoxy)-2-hydroxy-3-tert-butyIaminopropan noch weitaus überlegen. Als ganz besonders wertvoll hat sich dabei das l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-tert-butylaminopropan herausgestelltIn animal experiments on guinea pigs, the compounds of the formula I or their physiologically tolerable acid addition salts have excellent therapeutic, in particular /? -Adreno-ytic, properties shown and can therefore, for example, for the 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 known compounds such as l- (2-cyano-3-methylphenoxy) -2-hydroxy-3-isopropylaminopropane and l- (2-cyano-3-methyIphenoxy) -2-hydroxy-3-tert-butylaminopropane by far think. That has proven to be particularly valuable 1- (2-cyano-5-methylphenoxy) -2-hydroxy-3-tert-butylaminopropane

Die Einzeldosis der erfindungsgemäßen Substanzen liegt bei 0,5 bis 300 mg, vorzugsweise 1 bis 60 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 60 mg (orally) or 0.1 to 10 mg (parenteral).

Die überlegene Wirkung der erfindungsgemäßen Verbindungen gegenüber aus DE-AS 15 43357 und 16 43 237 bekannten strukturiihnlichen Derivaten ist der Tabelle I zu entnehmen.The superior action of the compounds according to the invention compared to DE-AS 15 43357 and 16 43 237 known structurally similar derivatives is the Table I can be found.

Verbindung (als HCI-SaIz)Connection (as HCI-SaIz) Isoprotcrenol-Isoprotcrenol

anlagonistischermore anlagonistic

Effekt*)Effect*)

A. Stand der TechnikA. State of the art

l-(2-Nitrilo-3-methylphenoxy)-2-hydroxy-3-isopropylaininopropan l-(2-Nitrilo-3-methylphenoxy)-2:hydroj' -t-butylaminopropan l-(2-NitriIo-3-methylphenoxy)-2-hydroxy-3-s-butylaminopropan l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-3-isopropylaminopropan1- (2-Nitrilo-3-methylphenoxy) -2-hydroxy-3-isopropylaminopropane 1- (2-Nitrilo-3-methylphenoxy) -2 : hydroj '-t-butylaminopropane 1- (2-NitriIo-3-methylphenoxy) -2-hydroxy-3-s-butylaminopropane 1- (2-nitrilo-5-methylphenoxy) -2-hydroxy-3-isopropylaminopropane

B. ErfindungsgemäßB. According to the invention

l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-3-s-butylaminopropan l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-t-butylaminopropan l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-3-(l,l-dimethyl-ii-propylamino)-propan l-(2-Nitrilo-5-methylphenoxy)-2-hydroxy-3-(l,l-dimethyl-n-butylamino)-propan1- (2-nitrilo-5-methylphenoxy) -2-hydroxy-3-s-butylaminopropane 1- (2-nitrilo-5-methylphenoxy) -2-hydroxy-t-butylaminopropane 1- (2-Nitrilo-5-methylphenoxy) -2-hydroxy-3- (1,1-dimethyl-II-propylamino) propane 1- (2-Nitrilo-5-methylphenoxy) -2-hydroxy-3- (1,1-dimethyl-n-butylamino) propane

*) Die Tests wurden an lebenden Meerschweinchen durchgeführt. Als Standardsubstanz diente 3,4· (DCI), dessen Wirkung gleich 1 gesetzt wurde.*) The tests were carried out on live guinea pigs. 3.4 (DCI), the effect of which was set equal to 1.

55fach DCI 60fach DCl Hfach DCl 43fach DCI55x DCI 60-fold DCl Hfach DCl 43-fold DCI

74fach DCI 77? fach DCI 130fach DCI74x DCI 77? fold DCI 130x DCI

47fach DCI Dichlorisoproterenol47x DCI Dichloroisoproterenol

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 galenic processing of the compounds according to the invention or their acid addition salts to give the Usual application forms such as solutions, emulsions, tablets, coated tablets or depot forms can be used in known way using the galenic auxiliary, carrier, explosive, Binding agents, coating agents or lubricants, flavorings, sweeteners, agents for making 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-hydrochlorid1- (2-cyano-5-methylphenoxy) -2-hydroxy-3-sec-butylaminopropane hydrochloride

Aus 6,5 g (0,02MoI) l-(2-Amino-5-methyl· phenoxy)-2-hydoxy-3-sek.-butylaminopropan dihydrochlorid, 10 ml konz. HCI und 40 ml H2O, 2,8 g (0,04 Mol) NaNO2 und 10 ml H2O wird eine DiazoniumFrom 6.5 g (0.02 mol) 1- (2-amino-5-methyl-phenoxy) -2-hydoxy-3-sec-butylaminopropane dihydrochloride, 10 ml conc. HCl and 40 ml of H 2 O, 2.8 g (0.04 mol) of NaNO 2 and 10 ml of H 2 O is a diazonium salzlösung hergestellt. Diese wird in eine 90° C heiße Lösung aus 10 g Kupfersulfate 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 CHCb wird die CHCI3-Lösung über MgSO4 getrocknet, dann das CHCI3 abdesiilliert Der Rückstand wird durch Säulenchromatographie (z. B. Kieselgel) gereinigt Nach Eindampfen der Fraktionen mit einheitlicher Substanz v/ird die verbleibende Base in wenig Äther gelöst und mit ätherischer HCl angesäuert. Das ausfallende Hydrochlorid wird aus Äthanol unter Zugabe von Äther umkristallisiert. Ausbeute: 1,8 g; F = 113bisll5°C.saline solution made. 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, it is made alkaline, resinous components which precipitate are separated off.After extraction with CHCb, 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. silica gel) Substance v / ird the remaining base is dissolved in a little ether and acidified with ethereal HCl. The precipitated hydrochloride is recrystallized from ethanol with the addition of ether. Yield: 1.8 g; F = 113 to 115 ° C.

Beispiel 2Example 2

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

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

NaNQa in 15 ml H2O bei 0 bis 50C diazotiert Dip Diazoniumsalzlösung wird in eine auf 9O0C erhitzte Lösung aus 15 g Kupfersulfat, 16,8 g KCN und 90 ml H2O eingerührt und 30 Minuten bei 85 bis 90" C nachgerührt Nach Abkühlen wird mit NaOH alkalisch gestellt Das Ganze wird mit CHCI3 extrahiert, verharzte Anteile und die wäßrige Phase werden abgetrennt Nach Waschen der organischen Phase mit H2O wird über MgSO4 getrocknet Das CHCl3 wird abdestilliert, wobei 6,8 g Rohsubstanz verbleiben. Sie wird aus Äthanol unter Zugabe von Äther umkristallisiert NaNQa diazotized in 15 ml H 2 O at 0 to 5 0 C. Dip diazonium salt solution is stirred into a heated to 90 0 C solution of 15 g copper sulfate, 16.8 g KCN and 90 ml H 2 O and 30 minutes at 85 to 90 " 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 CHCl 3 is distilled off, with 6.8 g The raw substance remains and 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-hydroch!orid 1- (2-cyano-5-methylphenoxy) -2-hydroxy-3- (l, l-dimethylpropylamino) propane hydrochloride

Aus 10,2 g (0,03 Mol) 1-(2-Amino-5-methylphenoxy)-2-hydroxy-3-(l,l-dimethylpropylamino)-prupan-dihydrochlorid, 15 ml konz. HCl und 60 ml H2O und 4,2 g (0,06 Mol) NaNO2 in 15 ml H2O wird eine Diazoniumlösuiig 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. 900C gehalten. Nach Abkühlen wird alkalisch gemacht und mit CHCb ausgeschüttelt. Unlösliche Anteile und die wäßrige Phase werden abgetrennt Nach Trocknen der CHC'b-Lösung üb";r 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-dimethylpropylamino) -prupane 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 CHCb. 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 Ether dissolved The hydrochloride precipitates in crystalline form by adding ethereal HCl and is recrystallized from ethanol with the addition of ether.
Yield: 2.2 g; mp = 187-188 ° C.

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)-23-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. HCI angesäuert und unlösliche Anteile abfiltriert Das Filtrat wird mit NaOH alkalisch gestellt, w obei die freiwerdende Base kristallin ausfällt Sie wird isoliert, getrachtet 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 162° C.7.45 grams (0.0395 moles) of 1- (2-cyano-5-methylphenoxy) -23-epoxypropane are dissolved in 60 ml of ethanol, 9 g (0.2 mol) of ethylamine are added and two under reflux Heated to the boil for hours. After cooling, the solvent is distilled off in vacuo and the residue is removed acidified with dil. HCl and insoluble components filtered off. The filtrate is made alkaline with NaOH, w obei the base liberated precipitates in crystalline form. It is isolated, sought and from ethyl acetate with the addition of Recrystallized petroleum ether The crystals are then dissolved in a little acetonitrile, ethereal HCl added and the precipitated hydrochloride filtered off with suction. Yield: 4.5 g; F = 160 to 162 ° C.

Beispiel 5Example 5

1 -(2-Cyano-5-methylphenoxy)-2-hydroxy-3-( 1,1 -dimethylbutylamino)-propan-hydrochlorid 1 - (2-Cyano-5-methylphenoxy) -2-hydroxy-3- (1,1-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) I.l-Dimethylbutylamin zugegeben und wie in Beispiel 4 umgesetzt und aufgearbeitet.
Ausbeute:5,7 g; F= 'HObis 1830C.7.45 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 II-dimethylbutylamine are added and as in Example 4 implemented and processed.
Yield: 5.7 g; F = 'HO to 183 0 C.

B, Formulierungsbeispiele
1. TablettenB, formulation examples
1. Tablets

Die Tabletten werden aus folgenden Bestandteilen J hergestellt:The tablets are made from the following ingredients J :

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

3-tert-butylaminopropan-hydrochlorid 20,0 g3-tert-butylaminopropane hydrochloride 20.0 g

Maisstärke 164,0 gCorn starch 164.0 g

m Calciumphosphat 240,0 gm calcium phosphate 240.0 g

Magnesiumstearat 1,0 gMagnesium stearate 1.0 g

425,0 g425.0 g

Die einzelnen Bestandteile werden intensiv miteinander vermischt und die Mischung in üblicher Weise granuliert Das Granulat wird sodann zu 1000 Tabletten von 425 mg Gewicht verpreßt von denen jede 20 mg Wirkstoff enthältThe individual components are intensively mixed with one another and the mixture is mixed in the usual way granulated The granules are then compressed into 1000 tablets weighing 425 mg, each of which is 20 mg Contains active ingredient

jo 2. Gelatine-Kapselnjo 2. 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-maleinat
Maisstärke3-tert-butylaminopropane maleate
Cornstarch

25,0 mg 175,0 mg25.0 mg 175.0 mg

200,0 mg200.0 mg

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

3. Injektionslösung3. Solution for injection

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

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-3-tert-butylaminopropan-hydrochlorid 1,5 Teile1- (2-cyano-5-methylphenoxy) -2-hydroxy-3-tert-butylaminopropane hydrochloride 1.5 parts

Natriumsalz der Äthylendiamintetra-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 Äthylendiamintetraessigsäure werden in genügend Wasser gelöst und mit Wasser auf das gewünschte Volumen aufgefüllt Die 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. Depotdragaes> ') 4. Depotdragaes

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

l-(2-Cyano-5-methylphenoxy)-2-hydroxy-S-sele-butylarMnopropan-hydrochlorid
-,ι Carbocymethylcellulose
Stearinsäure
Celluloseacetatphthalat1- (2-Cyano-5-methylphenoxy) -2-hydroxy-S-sele-butyl-mnopropane hydrochloride
-, ι carbocymethyl cellulose
Stearic acid
Cellulose acetate phthalate

45,0 g45.0 g

295,0 g295.0 g

20,0 g20.0 g

40,0 g40.0 g

400,0 g400.0 g

Der Wirkstoff, die Carboxymethylcellulose und die Stearinsäure werden intensiv gemischt und die Mischung in üblicher Weise granuliert wobei man eine Lösung des cel'uloseacetatphthalats in 200 ml eines Gemisches aus Äthanoi/Äthylacetat verwendet Das 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.The active ingredient, the carboxymethyl cellulose and the stearic acid are mixed intensively and the mixture granulated in the usual way, a solution of cel'uloseacetatphthalats in 200 ml of a Mixture of ethanoi / ethylacetate used. The granulate is then pressed into 400 mg cores which are in Usually with a sugary 5% solution coated with polyvinylpyrrolidone in water. Each Drag6e contains 25 mg of active ingredient.

Claims (1)

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 the formula (I) CNCN ^0-CH2-CHOH-CH2-NHR (I)^ 0-CH 2 -CHOH-CH 2 -NHR (I) CNCN
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
BG015776A BG17293A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING SUBSTITUTED ALKYLAMINOPROPANE
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
BG018262A BG17294A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING NEW 1-<2-CYANO-5-METHYLPHENOXY>-2-HYDROXY-3-ALKYLAMINOPROPANES
BG018264A BG17295A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING SUBSTITUTED 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.
CH697773A CH553167A (en) 1969-10-06 1970-10-02 METHOD OF PREPARING NEW 1- (2'-CYANO-5'-METHYLPHENOXY) -2-HYDROXY-3-SEC.-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.
BG018265A BG17296A3 (en) 1969-10-06 1970-10-02 METHOD FOR OBTAINING SUBSTITUTED 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.
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.
CH546222D CH546222A (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.
ES384244A ES384244A1 (en) 1969-10-06 1970-10-03 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia
SU1705732A SU423291A3 (en) 1969-10-06 1970-10-05
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.
SU1481523A SU361563A1 (en) 1970-10-05 METHOD OF OBTAINING 1-
SU1705074A SU400081A1 (en) 1970-10-05 METHOD OF OBTAINING OPTICALLY ACTIVE
PL17334270A PL84642B1 (en) 1969-10-06 1970-10-05 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia [DE1950351A1]
SU1705733A SU421182A3 (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]
JP8675670A JPS501262B1 (en) 1969-10-06 1970-10-05
SU1705730A SU417938A3 (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
SE1347570A SE375094B (en) 1969-10-06 1970-10-05
PL14378570A PL84252B1 (en) 1969-10-06 1970-10-05 (cyano methylphenoxy) hydroxy alkylamino - propanes for coronary disease and hypertonia [DE1950351A1]
SU1705040A SU400082A1 (en) 1970-10-05 In PTB
SU1705731A SU422137A3 (en) 1969-10-06 1970-10-05 METHOD OF OBTAINING 1-
SU1699774A SU426360A3 (en) 1969-10-06 1970-10-05 METHOD OF OBTAINING 1-
RO6726970A RO59185A (en) 1969-10-06 1970-10-06
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
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
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
RO6728970A RO58550A (en) 1969-10-06 1970-10-06
RO6727270A RO58534A (en) 1969-10-06 1970-10-06
RO6727470A RO58549A (en) 1969-10-06 1970-10-06
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
RO6727070A RO58533A (en) 1969-10-06 1970-10-06
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
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
RO6726870A RO58532A (en) 1969-10-06 1970-10-06
RO6727370A RO58548A (en) 1969-10-06 1970-10-06
RO6461670A RO56983A (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
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
RO6727170A RO59186A (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
ES391141A ES391141A1 (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
ES391134A ES391134A1 (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
ES391140A ES391140A1 (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
ES391138A ES391138A1 (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
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)

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

Family

ID=5747463

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19691950351 Expired DE1950351C3 (en) 1969-08-05 1969-10-06 1- (2-Cyano-5-methylphenoxy) -2-hydroxy-3-aIkylaminopropane, process for their preparation and medicaments containing them

Country Status (13)

Country Link
JP (1) JPS501262B1 (en)
AT (10) AT306698B (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) PL84637B1 (en)
RO (9) RO59185A (en)
SE (1) SE375094B (en)
SU (6) SU421182A3 (en)
YU (1) YU34516B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI101950B (en) 1996-12-12 1998-09-30 Uponor Innovation Ab Method and apparatus for recovering recyclable plastic material i and plastic product made with a press device
RU2660811C1 (en) * 2017-03-21 2018-07-10 Общество с ограниченной ответственностью Научно-производственное предприятие "Резонанс" (ООО НПП "Резонанс") Induction electrical machine

Also Published As

Publication number Publication date
ES391139A1 (en) 1973-07-16
ES391134A1 (en) 1973-07-16
ES391135A1 (en) 1973-07-16
BG17531A3 (en) 1973-11-10
SU426360A3 (en) 1974-04-30
RO58533A (en) 1975-08-15
RO56983A (en) 1974-12-15
YU244470A (en) 1979-02-28
ES391141A1 (en) 1973-07-16
RO59185A (en) 1976-01-15
BG17294A3 (en) 1973-07-25
RO58550A (en) 1975-08-15
SU421182A3 (en) 1974-03-25
AT308072B (en) 1973-06-25
BG17529A3 (en) 1973-11-10
SU361563A3 (en) 1972-12-07
SU400081A3 (en) 1973-10-03
RO58548A (en) 1975-09-15
AT306698B (en) 1973-04-25
RO58532A (en) 1975-09-15
SE375094B (en) 1975-04-07
SU503507A3 (en) 1976-02-15
CH542814A (en) 1973-10-15
YU34516B (en) 1979-09-10
ES391140A1 (en) 1973-07-16
ES391136A1 (en) 1973-07-16
DE1950351B2 (en) 1978-04-27
AT306700B (en) 1973-04-25
SU422137A3 (en) 1974-03-30
AT306696B (en) 1973-04-25
PL84252B1 (en) 1976-03-31
ES384244A1 (en) 1973-01-01
SU423291A3 (en) 1974-04-05
BG17528A3 (en) 1973-11-10
AT306695B (en) 1973-04-25
BG17295A3 (en) 1973-07-25
CS162731B2 (en) 1975-07-15
SU400082A3 (en) 1973-10-03
AT306701B (en) 1973-04-25
RO59186A (en) 1976-01-15
PL84642B1 (en) 1976-04-30
DE1950351A1 (en) 1971-04-29
RO58534A (en) 1975-09-15
JPS501262B1 (en) 1975-01-16
RO58549A (en) 1975-08-15
AT302274B (en) 1972-10-10
AT306699B (en) 1973-04-25
DK128237B (en) 1974-03-25
BG17527A3 (en) 1973-11-10
AT306697B (en) 1973-04-25
BG17293A3 (en) 1973-07-25
BG17296A3 (en) 1973-07-25
ES391138A1 (en) 1973-07-16
ES391137A1 (en) 1973-07-16
AT306694B (en) 1973-04-25
SU417938A3 (en) 1974-02-28
PL84637B1 (en) 1976-04-30

Similar Documents

Publication Publication Date Title
DE1643262C3 (en) i-Phenoxy ^ -hydroxy-S-alklyaminopropane, process for their preparation and medicaments containing these compounds
DE2351412C2 (en) 2,2-Disubstituted 1-oxo-5-indanyloxy-carboxylic acids, processes for their preparation and resolution of racemic mixtures, and pharmaceuticals containing them
DE1937477B2 (en) 1-phenoxy-2-hydroxy-3- (1-methylcycloalkylamino) propane, process for their preparation and medicaments containing them
CH372667A (en) Process for the preparation of 3-aryl-3-pyrrolidinols
EP0132811B1 (en) 1-substituted 4-hydroxymethyl-pyrrolidinones, processes for their preparation, pharmaceutical composition and intermediate
DE1940566C3 (en) 1- (2-Nitrilophenoxy) -2-hydroxy-3ethylaminopropane, process for its preparation and pharmaceuticals containing it
DE2523103A1 (en) NEW PROPARGYL-2-PHENYLAMINO-IMIDAZOLINE- (2), THEIR ACID-ADDITIONAL SALTS, THESE MEDICINAL PRODUCTS AND METHOD FOR MANUFACTURING THE SAME
DE1815808B2 (en) 1 - (Alkanoylamiitophenoxy) -3-alkylamino-2-propanols, their manufacturing processes and pharmaceutical compositions based on them
DE1950351C3 (en) 1- (2-Cyano-5-methylphenoxy) -2-hydroxy-3-aIkylaminopropane, process for their preparation and medicaments containing them
CH628346A5 (en) Method for producing new xanthi derivatives.
DE3015991A1 (en) NEW 1-ARYLOXY-3-ALKYLAMINO-2-PROPANOLS AND METHOD FOR THE PRODUCTION THEREOF
EP0035733B1 (en) 1-(acylamino-aryloxy-)2-hydroxy-3-alkinyl-amino propanes and processes for their manufacture
EP0014996B1 (en) Heterocyclic spiro-amidines, their stereoisomers and optical isomers, methods for their preparation and medicaments containing them
EP0035734B1 (en) 1-(acylamino-aryloxy-)2-hydroxy-3-alkinyl-amino propanes and processes for their manufacture
DE1643237C3 (en) Nuclear-substituted 1-nitrilophenoxy-3-tert-butylamino-2-propanols, processes for their production and pharmaceutical preparations based on them
DE1643266C3 (en) 1 phenoxy 2 hydroxy 3 sec alkylamino propane, a process for their production and preparations containing them
DE2846880A1 (en) SUBSTITUTED QUINOLICIDINE AND INDOLICIDINE METHANOL DERIVATIVES, METHOD FOR MANUFACTURING THE SAME, AND MEDICINAL PRODUCTS CONTAINING THEM
DE2210620C2 (en) Bis-phenoxypropanolamines, process for their preparation and pharmaceuticals containing them
DE2158468A1 (en) New imidazoline compounds, processes for their production and pharmaceutical preparations containing them
DE1618160C3 (en) 1- (2-Ethynylphenoxy) -2-hydroxy-3alkylaminopropanes, their physiologically acceptable acid addition salts, processes for their preparation, and pharmaceuticals containing these compounds
DE1793799C2 (en) 1 -Phenoxy ^ -hydroxyO-alkylaminopropanes, process for their preparation and pharmaceuticals containing these compounds
CH615181A5 (en) Process for the preparation of novel ergolene derivatives
DE1910560A1 (en) New adamantane derivatives
EP0031456A1 (en) Substituted 4-amino-2,6-diaryl-tetrahydrothiopyranes, their acid-addition salts, processes for their preparation and pharmaceutical compositions
AT337180B (en) PROCESS FOR THE PREPARATION OF NEW 1,3-BENZO-DIOXOL DERIVATIVES AND THEIR SALTS

Legal Events

Date Code Title Description
C3 Grant after two publication steps (3rd publication)
8339 Ceased/non-payment of the annual fee