CH513796A - 2-substd-2-hydroxy cyclohexane cyclohexane carboxylic - Google Patents
2-substd-2-hydroxy cyclohexane cyclohexane carboxylicInfo
- Publication number
- CH513796A CH513796A CH757071A CH757071A CH513796A CH 513796 A CH513796 A CH 513796A CH 757071 A CH757071 A CH 757071A CH 757071 A CH757071 A CH 757071A CH 513796 A CH513796 A CH 513796A
- Authority
- CH
- Switzerland
- Prior art keywords
- coor
- phenyl
- cyclohexane
- gall
- treatment
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C62/02—Saturated compounds containing hydroxy or O-metal groups
- C07C62/04—Saturated compounds containing hydroxy or O-metal groups with a six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Vascular Medicine (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
(A)2-Substituted 2-hydroxy cyclohexane carboxylic acids of general formula (I): X = -COOR' or -CH2COOR'; When X = -COOR' R = phenyl or cyclohexyl R' = H or Where X = -CH2-COOR' R = phenyl R' = H or -CH2-CH2- (B) Salts of (I) with inorganic- and organic acids such as HCl, H2SO4, citric, malonic or tartaric acid and the quaternary ammonium salts of the esters with an alkylhalide or with methyl-p-toluenesulphonate. (C) Therapeutic preparations containing one or more of A and/or B together with inert fillers and/or therapeutically active compounds. (I) have choleretic- and antispastic activity; they have no hypotensive activity and are esp. suitable for the treatment of cramp in the gall ducts and bowels. They are therefore valuable therapeutics in the treatment of various diseases of gall and liver and of spastic conditions in the metabolic system, gall ducts, urinary tract and sexual organs.
Description
Verfahren zur Herstellung einer therapeutisch wirksamen Hydroxycyclohexancarbonsäure
Die Erfindung betrifft ein Verfahren zur Herstellung einer choleretisch wirksamen Säure.
Die neue Verbindung ist durch die folgende Formel dargestellt:
EMI1.1
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man 2-Phenyl-2-hydroxycyclohexancarbonsäure der Formel
EMI1.2
durch Hydrierung in die 2-Cyclohexyl-2-hydroxycyclohexancarbonsäure überführt.
Die choleretische Wirkung der Säure ist auf Grund vielfacher, an der Ratte ausgeführter pharmakologischer Versuche nach dem Verfahren der Gallenfistel nachgewiesen worden und die Verbindung hat Steigungen des Gallenflusses pro Zeiteinheit in der Höhe von 100 bis 200 % bewirkt, ohne eine Verminderung der Konzentration das Exkreta bildenden Bestandteile zu bewirken.
Die pharmakologische Wirkung der untersuchten Verbindung zeigt sich durch eine starke Steigerung bei der Verabreichung und dauert 2 bis 3 Stunden an.
Beispiel
25 g 2-Hydroxymethylcyclohexanon, verdünnt in 200 cm3 Äther, werden tropfenweise in einen Behälter, enthaltend eine Ätherschwemme aus Phenyl-Magnesium-Bromid (aus 19,6 g Magnesium und 128 g Brombenzol in 300 cm3 Äther gemäss bekannter Verfahren hergestellt), unter Umrühren und Aussenkühlung mit Eis zugegeben. Man rührt noch einige Zeit weiter und fällt dann den Magnesium-Komplex durch vorsichtiges Eingeben in Wasser und Eis aus; man solubilisiert das Hydrat in Magnesium mit 50 cm3 einer gesättigten Lösung Ammoniumchlorid, fällt die Ätherschicht aus und extrahiert mit weiterem Äther den Wasseranteil.
Die Ätherextrakte, vereinigt und getrocknet, werden eingedampft und der Rückstand im Vakuum ergibt 15 g eines dickflüssigen Öles mit Siedepunkt 127 bis 1350 C bei 0,1 bis 0,2 mm Hg.
Dieses Erzeugnis kristallisiert durch Lösung in Äther und Fällung mit Petroläther, unter Erhalt von 7 g 1 -Phenyl-2-hydroxymethylcyclohexanol. Schmelzpunkt (Kofler): 21 bis 830 C.
Der so erhaltene Alkohol wird nach Trocknung und feiner Zerpulverung in 1,4 Liter einer wässrigen Lösung aus 14 g KMnO4 und 7 g Ka2CO3 suspendiert und die Suspension 1 Tag lang heftig gerührt.
Alsdann wird das entstandene MnO2 gefiltert und dem Filtrat wird etwas Na2SO2 bis zum Verschwinden der violetten Färbung zugesetzt; alsdann wird erneut das MnO2 abfiltriert und die alkalische Lösung mit konzentriertem HC1 angesäuert.
Nach dem Stehenlassen während eines Tages im Kühlschrank wird filtriert und mit Wasser gewaschen und so 5 g 2Phenyl-2-hydroxycyclohexancarbonsäure erhalten. Schm,elzpunkt (Kofler): 143 bis 1450 C.
5,6 g 2- Phenyl-2-hydroxycyclohexancarbonsäure werden in etwa 75 cm3 Eisessig gelöst und im Autoklav in Gegenwart von 0,1 g Platinoxyd unter Wasserstoff druck von 22 kg/cm2 bei Temperatur von 70 bis 800 C hydriert.
Nach Beendigung der Aufnahme des Wasserstoffes wird die Lösung filtriert und auf 1/5 seines Wertes eingedampft und im Kühlschrank gekühlt. Das gefällte Erzeugnis wird filtriert und mit Wasser gewaschen und aus Ligroin auskristallisiert, unter Erhalt von 4 g 2 Cyclohexyl-2-hydroxycyclohexancarbonsäure. Schmelzpunkt (Kofler): 122 bis 1240 C.
Process for the preparation of a therapeutically active hydroxycyclohexanecarboxylic acid
The invention relates to a process for the preparation of a choleretically active acid.
The new compound is represented by the following formula:
EMI1.1
The process according to the invention is characterized in that 2-phenyl-2-hydroxycyclohexanecarboxylic acid of the formula
EMI1.2
converted into 2-cyclohexyl-2-hydroxycyclohexanecarboxylic acid by hydrogenation.
The choleretic effect of the acid has been proven on the basis of multiple pharmacological tests carried out on rats using the biliary fistula method, and the compound has caused increases in the flow of bile per unit of time of 100 to 200% without reducing the concentration of the excreta To effect components.
The pharmacological effect of the tested compound is shown by a large increase in the administration and lasts for 2 to 3 hours.
example
25 g of 2-hydroxymethylcyclohexanone, diluted in 200 cm3 of ether, are poured drop by drop into a container containing a glut of ether made of phenyl magnesium bromide (made from 19.6 g of magnesium and 128 g of bromobenzene in 300 cm3 of ether according to known methods), while stirring and external cooling with ice added. The mixture is stirred for a while and then the magnesium complex is precipitated by carefully pouring it into water and ice; the hydrate is solubilized in magnesium with 50 cm3 of a saturated solution of ammonium chloride, the ether layer is precipitated and the water content is extracted with more ether.
The ether extracts, combined and dried, are evaporated and the residue in vacuo gives 15 g of a viscous oil with a boiling point of 127 to 1350 ° C. at 0.1 to 0.2 mm Hg.
This product crystallizes by dissolving in ether and precipitating with petroleum ether to give 7 g of 1-phenyl-2-hydroxymethylcyclohexanol. Melting point (Kofler): 21 to 830 C.
The alcohol thus obtained, after drying and finely pulverizing, is suspended in 1.4 liters of an aqueous solution of 14 g KMnO4 and 7 g Ka2CO3 and the suspension is vigorously stirred for 1 day.
The MnO2 formed is then filtered and some Na2SO2 is added to the filtrate until the violet color disappears; the MnO2 is then filtered off again and the alkaline solution is acidified with concentrated HC1.
After standing for one day in the refrigerator, it is filtered and washed with water to obtain 5 g of 2-phenyl-2-hydroxycyclohexanecarboxylic acid. Schm, elzpunkt (Kofler): 143 to 1450 C.
5.6 g of 2-phenyl-2-hydroxycyclohexanecarboxylic acid are dissolved in about 75 cm3 of glacial acetic acid and hydrogenated in the autoclave in the presence of 0.1 g of platinum oxide under hydrogen pressure of 22 kg / cm2 at a temperature of 70 to 800 C.
After the absorption of hydrogen has ended, the solution is filtered and evaporated to 1/5 of its value and cooled in the refrigerator. The precipitated product is filtered and washed with water and crystallized from ligroin to give 4 g of 2-cyclohexyl-2-hydroxycyclohexanecarboxylic acid. Melting point (Kofler): 122 to 1240 C.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT991366 | 1966-04-29 | ||
| CH562367A CH522592A (en) | 1966-04-29 | 1967-04-20 | 2-substd-2-hydroxy cyclohexane cyclohexane carboxylic |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH513796A true CH513796A (en) | 1971-10-15 |
Family
ID=25698102
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH63072A CH527153A (en) | 1966-04-29 | 1967-04-20 | Process for the preparation of therapeutically active hydroxycyclohexanecarboxylic acids |
| CH757071A CH513796A (en) | 1966-04-29 | 1967-04-20 | 2-substd-2-hydroxy cyclohexane cyclohexane carboxylic |
| CH757171A CH532021A (en) | 1966-04-29 | 1967-04-20 | Process for the preparation of therapeutically active hydroxycyclohexanecarboxylic acid esters |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH63072A CH527153A (en) | 1966-04-29 | 1967-04-20 | Process for the preparation of therapeutically active hydroxycyclohexanecarboxylic acids |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH757171A CH532021A (en) | 1966-04-29 | 1967-04-20 | Process for the preparation of therapeutically active hydroxycyclohexanecarboxylic acid esters |
Country Status (1)
| Country | Link |
|---|---|
| CH (3) | CH527153A (en) |
-
1967
- 1967-04-20 CH CH63072A patent/CH527153A/en not_active IP Right Cessation
- 1967-04-20 CH CH757071A patent/CH513796A/en not_active IP Right Cessation
- 1967-04-20 CH CH757171A patent/CH532021A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH532021A (en) | 1972-12-31 |
| CH527153A (en) | 1972-08-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |