DE1966513A1 - 1-(3-hydroxymethyl-phenoxy)-2-hydroxy-3 sec - -butylaminopropane - prepd from substd epoxypropane and butylamine sh - Google Patents

1-(3-hydroxymethyl-phenoxy)-2-hydroxy-3 sec - -butylaminopropane - prepd from substd epoxypropane and butylamine sh

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Publication number
DE1966513A1
DE1966513A1 DE19691966513 DE1966513A DE1966513A1 DE 1966513 A1 DE1966513 A1 DE 1966513A1 DE 19691966513 DE19691966513 DE 19691966513 DE 1966513 A DE1966513 A DE 1966513A DE 1966513 A1 DE1966513 A1 DE 1966513A1
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DE
Germany
Prior art keywords
sec
hydroxy
phenoxy
hydroxymethyl
butylamine
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.)
Pending
Application number
DE19691966513
Other languages
German (de)
Inventor
Herbert Dr Koeppe
Werner Dr Kummer
Helmut Dr Staehle
Werner Dr Traunecker
Karl Prof 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
Application filed by CH Boehringer Sohn AG and Co KG filed Critical CH Boehringer Sohn AG and Co KG
Priority to DE19691966513 priority Critical patent/DE1966513A1/en
Publication of DE1966513A1 publication Critical patent/DE1966513A1/en
Pending legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03B—APPARATUS OR ARRANGEMENTS FOR TAKING PHOTOGRAPHS OR FOR PROJECTING OR VIEWING THEM; APPARATUS OR ARRANGEMENTS EMPLOYING ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ACCESSORIES THEREFOR
    • G03B1/00—Film strip handling
    • G03B1/02—Moving film strip by pull on end thereof
    • G03B1/04—Pull exerted by take-up spool
    • G03B1/10—Pull exerted by take-up spool rotated by knob through gearing

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  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Title cpd. (I) and its acid-addn. salts, are pref. pred. by reacting a cpd. (II): with sec. butylamine in ethanol (whwere Z is or -CH(OH)-CH2-hal). Cpd. (I) may be used in treatment and prophylaxis of coronary diseases and in the treatment of heart arrythmias es. tachycardia in humans. In an example, (I) is prepd. from 1-(3-hydroxymethylphenoxy)-2,3-epoxypropane and sec. butylamine.

Description

1-(3-Hydroxymethyl-phenoxy)-2-hydroxy-3-sek.-butylamino-propan, dessen Säureadditionssalze, Verfahren zu deren Herstellung und diese enthaltende Prëparate (Ausscheidung aus P 16 43 266.9-42) Die Erfindung betrifft 1-(3-Hydroxymethyl-phenoxy)-2-hydroxy-3-sek.-butylamino-propan und dessen Säureadditionssalze; ein Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel.1- (3-Hydroxymethyl-phenoxy) -2-hydroxy-3-sec-butylamino-propane, its Acid addition salts, processes for their preparation and preparations containing them (Separated from P 16 43 266.9-42) The invention relates to 1- (3-hydroxymethyl-phenoxy) -2-hydroxy-3-sec-butylamino-propane and its acid addition salts; a process for their preparation and containing them Drug.

Die neue Verbindung kann durch Umsetzung einer Verbindung der allgemeinen Formel in der Z die Gruppe oder -CH(OH)-CH2-Hal und Hal ein Halogenatom bedeutet, mit sek.-Butylamin hergestellt werden.The new compound can be prepared by reacting a compound of the general formula in the Z the group or -CH (OH) -CH2-Hal and Hal is a halogen atom, can be prepared with sec-butylamine.

Ein Epoxid der Formel I läßt bich leichtdurch Umsetzung von Epichlorhydrin mit 3-Hydroxymethylphenol bzw. -phenolat herstellen. Durch Umsetzung es oxids der Formel I mit Halogenwasserstoffsäuren sind die entsprechenden Halogenhydride der Formel I darstellbar.An epoxide of the formula I can easily be converted into epichlorohydrin with 3-hydroxymethylphenol or phenolate. By implementing it oxides the Formula I with hydrohalic acids are the corresponding halohydrides of Formula I can be represented.

Die erfindungsgemäße Verbindung besitzt ein asymmetrisches Kohlenstoffatom und kornint daher als Racemat wie auch in Form der optischen Antipoden vor. Letztere können außer durch Racematentrennung mit Hilfe von üblichen Hilfssäuren wie Dibenzoyl-D-weinsäure oder D-3-Bromcampher-8-sulfonsäure auch durch Einsetzen von optisch aktivem Ausgangsmaterial erhalten werden. Das erfindungsgemäße l-( 3-Hydroxymethylphenoxy)-2-hydroxy-3-sek.-butylamino-propan kann in üblicher Weise in die physiologisch verträglichen Säureadditionssalze überführt werden. Geeignete Säuren sind beispielsweise Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Methansulfonsäure, Maleinsäure, Essigsäure, Oxalsäure, Milchsäure, Weinsäure oder 8-Chlortheophyllin.The compound of the invention has an asymmetric carbon atom and therefore occurs as a racemate as well as in the form of the optical antipodes. Latter can, in addition to racemate resolution with the aid of customary auxiliary acids such as dibenzoyl-D-tartaric acid or D-3-bromocamphor-8-sulfonic acid also by using optically active starting material can be obtained. The l- (3-hydroxymethylphenoxy) -2-hydroxy-3-sec-butylamino-propane according to the invention can be converted into the physiologically acceptable acid addition salts in the usual way will. Suitable acids are, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, Methanesulfonic acid, maleic acid, acetic acid, oxalic acid, lactic acid, or tartaric acid 8-chlorotheophylline.

Die erfindungsgemäße Verbindung bzw. deren physiologisch verträglichen Säureadditionssalze haben im Tierversuch an Meerschweinchen wertvolle therapeutische, insbesondere B-adrenolytische Eigenschaftn gezeigt und können daher beispielsweise zur Behandlung der Propylaxe von Erkrankungen der Herzkranzgefäße und zur Behandlung von Herzarrythmien,insbesondere von Tachycardien, in der Humanmedizineingesetzt werden. Auch die blutdrucssenkenden Eigenscnaften der Verbindung sind therapeutisch interessant.The compound according to the invention or its physiologically compatible In animal experiments on guinea pigs, acid addition salts have valuable therapeutic, in particular shown B-adrenolytic properties and can therefore, for example for the treatment of prophylaxis of diseases of the coronary arteries and for treatment of cardiac arrhythmias, in particular of tachycardias, are used in human medicine will. The blood pressure lowering properties of the compound are also therapeutic Interesting.

Vergleichsversuch Die Prüfung auf isoproterenol-antagonistische Wirkung erfolgte an lebenden Meerschweinchen. Als Standardsubstanz diente 3,4-Dichlorisoproterenol (DCI), dessen Wirkung gleich 1 gesetzt wurde. Comparative experiment The test for isoproterenol-antagonistic effect took place on live guinea pigs. 3,4-dichloroisoproterenol was used as the standard substance (DCI), the effect of which was set equal to 1.

Verbindung (als HCl-Salz) isoproterenol-antagon.Compound (as HCl salt) isoproterenol-antagon.

Wirkung A. Stand der Technik (Belg. P. 641 133 und Belg. P. 652 336) 1-m-Tolyloxy-2-hydroxy-3-isopropylaminopropan (Wirkstoff des Doberol (R)) 5 x DCI B. Erfindung 1-(3'Hydroxymethyl-phenoxy)-2-hydroxy-3-sek.-butylaminopropan 13,0 x DCI Die Einzeldosis der erfindungsgemäßen Substanz liegt bei 1 bis 300 ng; vorzugsweise 5 bis 100 mg (oral) bzw. 1 bis 20 mg (parenteral). Effect A. State of the art (Belg. P. 641 133 and Belg. P. 652 336) 1-m-tolyloxy-2-hydroxy-3-isopropylaminopropane (active ingredient of Doberol (R)) 5 x DCI B. Invention 1- (3'-hydroxymethyl-phenoxy) -2-hydroxy-3-sec-butylaminopropane 13.0 x DCI The single dose of the substance according to the invention is 1 to 300 ng; preferably 5 to 100 mg (oral) or 1 to 20 mg (parenteral).

Die galeni sche Verarbeitung der erfindungsgemäßen Verbindungen erfolgt in üblicher Weise. Die Formulierungen enthalten beispielsweise 9 oder 12,5% des Wirkstoffs.The galenic processing of the compounds according to the invention takes place in the usual way. The formulations contain, for example, 9 or 12.5% des Active ingredient.

Die folgenden Beispiele erläutern die Erfindung.The following examples illustrate the invention.

1-(3-Hydroxymethylphenoxy)-2-hydroxy-3-sek. butylamino-propan 11,6 g (0,064 Mol) 1-(3-Hydroxymethylphenoxy)-2,3-expoxypropan werden in 100 ml Äthanol gelöst und nach Zugabe von 8,8 g (0,12 Mol) sek. Butylamin 3 Stunden unter Rückfluß gekocht. Nach Abdestillieren des Lösungsmittels im Vakuum verbleibt ein öliger Rückstand, der in wenig Äthanol gelöst, mit Äther versetzt wird.1- (3-hydroxymethylphenoxy) -2-hydroxy-3-sec. butylamino propane 11.6 g (0.064 mol) of 1- (3-hydroxymethylphenoxy) -2,3-expoxypropane are dissolved in 100 ml of ethanol dissolved and after the addition of 8.8 g (0.12 mol) sec. Butylamine under reflux for 3 hours cooked. After the solvent has been distilled off in vacuo, an oily residue remains, which is dissolved in a little ethanol and mixed with ether.

Die Base scheidet sich=kristallin ab und wird noch zweimal aus Äthanol/Äther umkristallisiert.The base separates out = crystalline and is made twice more from ethanol / ether recrystallized.

Analyse C H N Berechnet: 66,15% 9,89% 5,73% Gefunden: 66,3 % 9.76% 5,81% Ausbeute: 11,5 g, Fp: 73 - 750 G.Analysis C H N Calculated: 66.15% 9.89% 5.73% Found: 66.3% 9.76% 5.81% yield: 11.5 g, m.p .: 73-750 g.

1. Tabletten 1- ( 3-Hydroxymethyl-phenoxy)-2-hydroxy-3-sek.1. Tablets 1- (3-hydroxymethyl-phenoxy) -2-hydroxy-3-sec.

butylaminopropan . HC1 40,0 mg Maisstärke 164,0 mg sek. Calciumphosphat 240,0 mg Magnesiumstearat 1,0 mg 445,0 mg Herstellung: Die einzelnen Bestandteile werden intensiv miteinander vermischt und die Mischung in üblicher Weise granuliert. Das Granulat wird zu Tabletten von 445 mg Gewicht verpreßt, von denen jede 40 mg Wirkstoff enthält. butylaminopropane. HC1 40.0 mg corn starch 164.0 mg sec. Calcium phosphate 240.0 mg magnesium stearate 1.0 mg 445.0 mg Manufacture: The individual Components are intensively mixed with one another and the mixture in the usual way Way granulated. The granules are compressed into tablets weighing 445 mg, from each containing 40 mg of active ingredient.

2. Gelatine-Kapseln Der Inhalt der Kapseln setzt sich wie folgt zusammen: 1- ( 3-Hydroxymethyl-phenoxy) -2-hydroxy-3-sek. butylaminopropan . HC1 25,0 mg Maisstärke 175,0 mg 200,0 mg Herstellung: Die Bestandteile des Kapselinhalts werden intensiv vermischt und 200 mg-Portionen der Mischung werden in Gelatine-Kapseln geeigneter Größe abgefüllt.2. Gelatine capsules The contents of the capsules are made up as follows: 1- (3-hydroxymethyl-phenoxy) -2-hydroxy-3-sec. butylaminopropane. HC1 25.0 mg corn starch 175.0 mg 200.0 mg Preparation: The components of the capsule contents become intense mixed and 200 mg servings of the mixture in gelatin capsules will be more suitable Bottled size.

Jede Kapsel enthält 25 mg des Wirkstoffs.Each capsule contains 25 mg of the active ingredient.

Claims (3)

PatentansprücheClaims 1. (3-Hydroxymethyl-phenoxy)-2-hydroxy-3-sek.-butylaminopropan sowie dessen Säureadditionssalze.1. (3-Hydroxymethyl-phenoxy) -2-hydroxy-3-sec-butylaminopropane and its acid addition salts. 2. Verfahren zur Herstellung von l-(3-Hydroxymethyl-phenoxy)-2-hydroxy-3-sek.-butylamino-propan und dessen Säureadditionssalzen, dadurch gekennzeichnet, daß man in an sich bekannter Weise eine Verbindung der allgemeinen Formel in der Z die Gruppe oder -CH(OH)-CH2-Hal und Hal ein Halogenatom Decteutet, mit sek.-Butylamin umsetzt und gewUnschtenfalls die erhaltene Verbindung in ein Säureadditionssalz überführt.2. Process for the preparation of l- (3-hydroxymethyl-phenoxy) -2-hydroxy-3-sec-butylamino-propane and its acid addition salts, characterized in that a compound of the general formula is used in a manner known per se in the Z the group or -CH (OH) -CH2-Hal and Hal denotes a halogen atom, reacts with sec-butylamine and, if desired, converts the compound obtained into an acid addition salt. 3. Pharmazeutische Präparate, enthaltend als Wirkstoff 1-(3-Hydroxymethy1-phenoxy)-2-hydroxy-3-sek.-butylaminopropan bzw. dessen Säureadditionssalze.3. Pharmaceutical preparations containing 1- (3-hydroxymethy1-phenoxy) -2-hydroxy-3-sec-butylaminopropane as active ingredient or its acid addition salts.
DE19691966513 1969-08-19 1969-08-19 1-(3-hydroxymethyl-phenoxy)-2-hydroxy-3 sec - -butylaminopropane - prepd from substd epoxypropane and butylamine sh Pending DE1966513A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19691966513 DE1966513A1 (en) 1969-08-19 1969-08-19 1-(3-hydroxymethyl-phenoxy)-2-hydroxy-3 sec - -butylaminopropane - prepd from substd epoxypropane and butylamine sh

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19691966513 DE1966513A1 (en) 1969-08-19 1969-08-19 1-(3-hydroxymethyl-phenoxy)-2-hydroxy-3 sec - -butylaminopropane - prepd from substd epoxypropane and butylamine sh

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DE1966513A1 true DE1966513A1 (en) 1973-05-24

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4665094A (en) * 1985-08-29 1987-05-12 Merck & Co., Inc. Oculoselective beta-blockers for treatment of elevated intraocular pressure
US4945182A (en) * 1985-12-24 1990-07-31 Merck & Co., Inc. Oculoselective beta-blockers

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4665094A (en) * 1985-08-29 1987-05-12 Merck & Co., Inc. Oculoselective beta-blockers for treatment of elevated intraocular pressure
US4945182A (en) * 1985-12-24 1990-07-31 Merck & Co., Inc. Oculoselective beta-blockers

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