CH551998A - Esters and salts of cholic acid derivs - having choleretic activity - Google Patents

Esters and salts of cholic acid derivs - having choleretic activity

Info

Publication number
CH551998A
CH551998A CH1408571A CH1408571A CH551998A CH 551998 A CH551998 A CH 551998A CH 1408571 A CH1408571 A CH 1408571A CH 1408571 A CH1408571 A CH 1408571A CH 551998 A CH551998 A CH 551998A
Authority
CH
Switzerland
Prior art keywords
acid
dithiolane
salts
coo
vacuo
Prior art date
Application number
CH1408571A
Other languages
German (de)
Original Assignee
Medichemie Ag
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 Medichemie Ag filed Critical Medichemie Ag
Priority to CH1408571A priority Critical patent/CH551998A/en
Priority to SE7209401A priority patent/SE378811B/xx
Priority to US00272156A priority patent/US3846411A/en
Priority to GB3358672A priority patent/GB1388427A/en
Priority to BE786477A priority patent/BE786477A/en
Priority to FR7226261A priority patent/FR2148002B1/fr
Priority to DK359972AA priority patent/DK135721B/en
Priority to AT638572A priority patent/AT325789B/en
Priority to CA147,854A priority patent/CA969173A/en
Priority to IL39999A priority patent/IL39999A0/en
Priority to NL7210586A priority patent/NL7210586A/xx
Priority to DE2238304A priority patent/DE2238304C3/en
Priority to ES405492A priority patent/ES405492A1/en
Priority to US492713A priority patent/US3910888A/en
Publication of CH551998A publication Critical patent/CH551998A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)

Abstract

Title cpds. are of formula (I) or (II): A-COO-Alk-NR1R2.HOOC-B (I) A-COOH.R2R1N-Alk-OOC-B (II) (where A-COO is a bile acid radical, B-COO is the radical of an acid which has choleretic activity synergistic with that of the bile acid; Alk is ethylene, propylene or isopropylene, and R1 and R2 are independently H or lower alkyl, or NR1R2 forms a heterocyclic ring opt. contg. N or O as additional heteroatoms, and opt. substd. by alkyl radicals). A-COOH is pref. cholic, deoxycholic, chenodeoxycholic, dehydrocholic or lithocholic acid. B-COOH is pref. 1,2-dithiolan-3-valerianic acid, cinnamic acid (opt. substd. by 1-3 OH, lower alkoxy, lower acyloxy or halogen gps.), orotic acid or an S-contg. amino-acid, e.g. cysteine, methionine or arginine.

Description

       

  
 



   Die Erfindung betrifft ein Verfahren zur Herstellung eines neuen therapeutisch wirksamen Salzes der Formel
EMI1.1     
 worin A-COO den Rest einer Gallensäure, n = 2 oder 3 und R einen 1 bis 3 C-Atome enthaltenden aliphatischen Rest bedeuten.



   Die durch Salzbildung hergestellten neuen Verbindungen zeichnen sich vor allem durch leberschützende und choleretische Eigenschaften aus.



   Erfindungsgemäss wird das neue Salz aus   Dialkylaminoaikyl-    estern von Gallensäuren oder deren Säureadditionssalzen mit 1,2-Dithiolan-3-valeriansäure oder deren Salzen vorzugsweise in alkoholischer Lösung unter Erwärmen hergestellt und die entstandene klare Lösung danach in Vakuum eingedampft.



  Der kristallinische Rückstand kann mit Isopropyläther verdünnt, filtriert, gewaschen und in Vakuum getrocknet werden.



  Man gewinnt die gewünschten Salze mit einer Ausbeute von 80-90%.



   Beispiel 1
25 g Dehydrocholsäure-diäthylaminoäthylester (0,05 Mol) werden in 100 ml absolutem Äthanol suspendiert und unter Rühren mit einer Lösung von 10,5 g 1,2-Dithiolan-3-valeriansäure (0,05 Mol) in 50 ml Äthanol versetzt. Das Gemisch wird am Rückfluss erhitzt, worauf sich eine gelbe Lösung bildet. Sie wird heiss filtriert und danach im Vakuum das Lösungsmittel verdampft. Der kristallinische Rückstand wird mit 50 ml Isopropyläther verdünnt und abgesaugt, mit 20 ml Isopropyläther gewaschen und im Vakuum bei 500C getrocknet. Man erhält 28,7 g hellgelbe Kristalle, deren Zersetzungspunkt zwischen   180-1840C    liegt.



   Beispiel 2
Nach dem Verfahren des Beispiels 1 wird das Dehydrochol   säure-dimethylaminoäthylester- 1 ,2-dithiolan-3-valerat    in 88 %iger Ausbeute gewonnen.

 

   PATENTANSPRUCH



   Verfahren zur Herstellung eines Salzes von Gallensäuredialkylaminoalkylestern mit 1,2-Dithiolan-3-valeriansäure der Formel
EMI1.2     
 worin A-COO den Rest einer Gallensäure, n = 2 oder 3 und R einen 1 bis 3 C-Atome enthaltenden aliphatischen Rest bedeuten, dadurch gekennzeichnet, dass man einen basischen Ester einer Gallensäure oder dessen Säureadditionssalze der Formel
A-COO(CH2)n-NR2 mit   1,2-Dithiolan-3-valeriansäure    oder deren Salzen umsetzt.



   UNTERANSPRÜCHE
1. Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass als Lösungsmittel niedere aliphatische Alkohole verwendet werden.



   2. Verfahren nach Patentanspruch und Unteranspruch 1, dadurch gekennzeichnet, dass die Reaktion bei Siedehitze durchgeführt wird.

**WARNUNG** Ende DESC Feld konnte Anfang CLMS uberlappen**.



   



  
 



   The invention relates to a process for the preparation of a new therapeutically active salt of the formula
EMI1.1
 where A-COO is the radical of a bile acid, n = 2 or 3 and R is an aliphatic radical containing 1 to 3 carbon atoms.



   The new compounds produced by salt formation are mainly characterized by liver-protecting and choleretic properties.



   According to the invention, the new salt is prepared from dialkylaminoaikyl esters of bile acids or their acid addition salts with 1,2-dithiolane-3-valeric acid or their salts, preferably in alcoholic solution with heating, and the resulting clear solution is then evaporated in vacuo.



  The crystalline residue can be diluted with isopropyl ether, filtered, washed and dried in vacuo.



  The desired salts are obtained with a yield of 80-90%.



   example 1
25 g of dehydrocholic acid diethylaminoethyl ester (0.05 mol) are suspended in 100 ml of absolute ethanol and a solution of 10.5 g of 1,2-dithiolane-3-valeric acid (0.05 mol) in 50 ml of ethanol is added while stirring. The mixture is heated to reflux and a yellow solution forms. It is filtered hot and then the solvent is evaporated off in vacuo. The crystalline residue is diluted with 50 ml of isopropyl ether and filtered off with suction, washed with 20 ml of isopropyl ether and dried in vacuo at 50.degree. 28.7 g of light yellow crystals are obtained, the decomposition point of which is between 180-1840C.



   Example 2
Following the procedure of Example 1, the dehydrocholic acid dimethylaminoethyl ester 1,2-dithiolane-3-valerate is obtained in 88% yield.

 

   PATENT CLAIM



   Process for the preparation of a salt of bile acid dialkylaminoalkyl esters with 1,2-dithiolane-3-valeric acid of the formula
EMI1.2
 wherein A-COO is the radical of a bile acid, n = 2 or 3 and R is an aliphatic radical containing 1 to 3 carbon atoms, characterized in that a basic ester of a bile acid or its acid addition salts of the formula
A-COO (CH2) n-NR2 with 1,2-dithiolane-3-valeric acid or its salts.



   SUBCLAIMS
1. The method according to claim, characterized in that lower aliphatic alcohols are used as solvents.



   2. The method according to claim and dependent claim 1, characterized in that the reaction is carried out at boiling point.

** WARNING ** End of DESC field could overlap beginning of CLMS **.

Claims (1)

**WARNUNG** Anfang CLMS Feld konnte Ende DESC uberlappen **. ** WARNING ** Beginning of CLMS field could overlap end of DESC **. Die Erfindung betrifft ein Verfahren zur Herstellung eines neuen therapeutisch wirksamen Salzes der Formel EMI1.1 worin A-COO den Rest einer Gallensäure, n = 2 oder 3 und R einen 1 bis 3 C-Atome enthaltenden aliphatischen Rest bedeuten. The invention relates to a process for the preparation of a new therapeutically active salt of the formula EMI1.1 where A-COO is the radical of a bile acid, n = 2 or 3 and R is an aliphatic radical containing 1 to 3 carbon atoms. Die durch Salzbildung hergestellten neuen Verbindungen zeichnen sich vor allem durch leberschützende und choleretische Eigenschaften aus. The new compounds produced by salt formation are mainly characterized by liver-protecting and choleretic properties. Erfindungsgemäss wird das neue Salz aus Dialkylaminoaikyl- estern von Gallensäuren oder deren Säureadditionssalzen mit 1,2-Dithiolan-3-valeriansäure oder deren Salzen vorzugsweise in alkoholischer Lösung unter Erwärmen hergestellt und die entstandene klare Lösung danach in Vakuum eingedampft. According to the invention, the new salt is prepared from dialkylaminoaikyl esters of bile acids or their acid addition salts with 1,2-dithiolane-3-valeric acid or their salts, preferably in alcoholic solution with heating, and the resulting clear solution is then evaporated in vacuo. Der kristallinische Rückstand kann mit Isopropyläther verdünnt, filtriert, gewaschen und in Vakuum getrocknet werden. The crystalline residue can be diluted with isopropyl ether, filtered, washed and dried in vacuo. Man gewinnt die gewünschten Salze mit einer Ausbeute von 80-90%. The desired salts are obtained with a yield of 80-90%. Beispiel 1 25 g Dehydrocholsäure-diäthylaminoäthylester (0,05 Mol) werden in 100 ml absolutem Äthanol suspendiert und unter Rühren mit einer Lösung von 10,5 g 1,2-Dithiolan-3-valeriansäure (0,05 Mol) in 50 ml Äthanol versetzt. Das Gemisch wird am Rückfluss erhitzt, worauf sich eine gelbe Lösung bildet. Sie wird heiss filtriert und danach im Vakuum das Lösungsmittel verdampft. Der kristallinische Rückstand wird mit 50 ml Isopropyläther verdünnt und abgesaugt, mit 20 ml Isopropyläther gewaschen und im Vakuum bei 500C getrocknet. Man erhält 28,7 g hellgelbe Kristalle, deren Zersetzungspunkt zwischen 180-1840C liegt. example 1 25 g of dehydrocholic acid diethylaminoethyl ester (0.05 mol) are suspended in 100 ml of absolute ethanol and a solution of 10.5 g of 1,2-dithiolane-3-valeric acid (0.05 mol) in 50 ml of ethanol is added while stirring. The mixture is heated to reflux and a yellow solution forms. It is filtered hot and then the solvent is evaporated off in vacuo. The crystalline residue is diluted with 50 ml of isopropyl ether and filtered off with suction, washed with 20 ml of isopropyl ether and dried in vacuo at 50.degree. 28.7 g of light yellow crystals are obtained, the decomposition point of which is between 180-1840C. Beispiel 2 Nach dem Verfahren des Beispiels 1 wird das Dehydrochol säure-dimethylaminoäthylester- 1 ,2-dithiolan-3-valerat in 88 %iger Ausbeute gewonnen. Example 2 Following the procedure of Example 1, the dehydrocholic acid dimethylaminoethyl ester 1,2-dithiolane-3-valerate is obtained in 88% yield. PATENTANSPRUCH PATENT CLAIM Verfahren zur Herstellung eines Salzes von Gallensäuredialkylaminoalkylestern mit 1,2-Dithiolan-3-valeriansäure der Formel EMI1.2 worin A-COO den Rest einer Gallensäure, n = 2 oder 3 und R einen 1 bis 3 C-Atome enthaltenden aliphatischen Rest bedeuten, dadurch gekennzeichnet, dass man einen basischen Ester einer Gallensäure oder dessen Säureadditionssalze der Formel A-COO(CH2)n-NR2 mit 1,2-Dithiolan-3-valeriansäure oder deren Salzen umsetzt. Process for the preparation of a salt of bile acid dialkylaminoalkyl esters with 1,2-dithiolane-3-valeric acid of the formula EMI1.2 wherein A-COO is the radical of a bile acid, n = 2 or 3 and R is an aliphatic radical containing 1 to 3 carbon atoms, characterized in that a basic ester of a bile acid or its acid addition salts of the formula A-COO (CH2) n-NR2 with 1,2-dithiolane-3-valeric acid or its salts. UNTERANSPRÜCHE 1. Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass als Lösungsmittel niedere aliphatische Alkohole verwendet werden. SUBCLAIMS 1. The method according to claim, characterized in that lower aliphatic alcohols are used as solvents. 2. Verfahren nach Patentanspruch und Unteranspruch 1, dadurch gekennzeichnet, dass die Reaktion bei Siedehitze durchgeführt wird. 2. The method according to claim and dependent claim 1, characterized in that the reaction is carried out at boiling point.
CH1408571A 1971-08-04 1971-09-28 Esters and salts of cholic acid derivs - having choleretic activity CH551998A (en)

Priority Applications (14)

Application Number Priority Date Filing Date Title
CH1408571A CH551998A (en) 1971-09-28 1971-09-28 Esters and salts of cholic acid derivs - having choleretic activity
SE7209401A SE378811B (en) 1971-08-04 1972-07-17
US00272156A US3846411A (en) 1971-08-04 1972-07-17 Choleretically active esters and salts of bile acids
GB3358672A GB1388427A (en) 1971-08-04 1972-07-18 Bile acid derivatives and the manufacture thereof
BE786477A BE786477A (en) 1971-08-04 1972-07-19 ESTERS AND SALTS OF ACTIVITY GALLIC ACIDS
FR7226261A FR2148002B1 (en) 1971-08-04 1972-07-20
DK359972AA DK135721B (en) 1971-08-04 1972-07-20 Analogous process for the preparation of choleretically active esters or salts of bile acids.
AT638572A AT325789B (en) 1971-08-04 1972-07-25 Process for the preparation of new salts from gallic acid esters
CA147,854A CA969173A (en) 1971-08-04 1972-07-25 Choleretically active esters and salts of bile acids
IL39999A IL39999A0 (en) 1971-08-04 1972-07-26 Choleretically active esters and salts of bile acids
NL7210586A NL7210586A (en) 1971-08-04 1972-08-02
DE2238304A DE2238304C3 (en) 1971-08-04 1972-08-03 (Choleretically active) esters or salts of dehydrocholic acid, processes for their production and medicinal preparations containing these compounds
ES405492A ES405492A1 (en) 1971-08-04 1972-08-03 Choleretically active esters and salts of bile acids
US492713A US3910888A (en) 1971-08-04 1974-07-29 Choleretically active esters and salts of bile acids

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH1408571A CH551998A (en) 1971-09-28 1971-09-28 Esters and salts of cholic acid derivs - having choleretic activity

Publications (1)

Publication Number Publication Date
CH551998A true CH551998A (en) 1974-07-31

Family

ID=4397834

Family Applications (1)

Application Number Title Priority Date Filing Date
CH1408571A CH551998A (en) 1971-08-04 1971-09-28 Esters and salts of cholic acid derivs - having choleretic activity

Country Status (1)

Country Link
CH (1) CH551998A (en)

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