DE964049C - Process for the production of a spasmolytically effective salt of the ª ‡ -N- (ª ‰ -diaethylaminoaethyl) -aminophenylessigsaeureisoamylesters - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

ISSUED MAY 16, 1957

GERMAN PATENT OFFICE PATENT LETTERING

CLASS 12 p GROUP 810 INTERNAT. CLASS C 07 (1st

A 22457 IVb112 f

Dr. phil. nat. habil. Herbert Arnold, Bielefeld,

Dr. phil. Engelbert Kühas, Gadderbaum,

and Dr. med. Norbert Brock, Wadersloh (district of Beckum)

have been named as inventors

Asta-Werke Aktiengesellschaft Chemical Factory, Brackwede (Westphalia)

Process for the preparation of a spasmolytisdi effective salt of CE-N- (0-diethylaminoethyl) aminophenyl acetic acid isoamyl ester

Patented in the territory of the Federal Republic of Germany from 10. April .1905 at

Patent application published November 29, 1956

The patent was granted by geniadxt on May 2, 1957

The preparation of compounds of the aN - (/ 3-dialkylaminoalkyl) aminophenylacetic acid ester type is known from German patent specification 842 206. Of these compounds, in particular the a - N - (β -diethylaminoethyl) aminophenylacetic acid isoamyl ester of the following formula

C ₆ H ₆ -CH-COO C ₅ H ₁₁ (i)

NH-CH ₂ -CH ₂ -N (C ₂ H ₅ ) ₂

because of its excellent combined spasmolytic effect in spasms on the muscular how neural basis becomes important.

In investigations in which compounds of the c £ -N -. (/ 9-Diancylaminoalkyl) -aminophenylacetic acid ester on their ability to relate to others

combine pharmacologically active compounds, were tested, the compound of the above type was also tested with pyrazolone aminomethanesulfonic acids implemented. The 4-methylamino-2, 3-dimethyl-1-phenyl-pyrazolone- (5) -methanesulfonic acid- (4) the formula

CH,

HO.S. CH _a

the privilege.

: n -

CO

= C-CH ₃
N-CH ₃

C ₆ H ₆

709 514 / $ 17

In these experiments it has now been found that the α-N- (j8-diethylaminoethyl) aminophenylacetic acid isoamyl ester with the 4-methylamine- - 2, 3-dimethyl -1 - phenyl-pyrazolon- (5) -methanesulfonic acid- (4) reacts under salt exposure. This salt is water-soluble and pharmacologically acceptable and has a surprisingly increased pharmacological effectiveness.

It is known that the sodium salts of 4-methyl-amino-2, 3-dimethyl-i-phenyl-pyrazolone- (5) -methanesulfonic acid- (4) in addition to a predominant analgesic effect, a weakly myotropic spasmolytic effect Have an effect. While, however, with regard to the spasmolytic effect, the middle one effective dose of 4-methylamino-2,3-dimethyli-phenyl-pyrazolone- (5) methane sulfonic acid (4) component alone is about 1: 500 to 1: 1000 and the mean effective dose of the a-N - (/? - diethylamino - ethyl) - aminophenyl acetic acid isoamyl ester alone is 1: 225,000, the corresponding is Dose of the 4-methyl-amino-2, 3-dimethyl-i-phenyl-pyrazolone- (5) -methane-sulfonic acid- (4) -salt of a-N - (/ S-diethylanimoäthylJ-amitiophenylessigsäureisoamylester about 1: 480,000. The salt shows an increase in effectiveness of more than double compared to the individual components. It deals It is therefore not a question of a mere addition of the individual effects, the spasmolytic effects Rather, the individual components of the salt formed experience a potentiation in this combination, which has also been confirmed in clinical trials.

The salt is prepared according to the invention in such a way that equivalent amounts of a water-soluble Salt, preferably the sodium salt of the pyrazolone - aminomethane - sulfonic acid component in aqueous solution with an acid salt, preferably with the sulfate of the ester base, combined. Included An aqueous salt forms with the deposition of the inorganic salt, for example sodium sulfate Solution of the pyrazolonaminomethane-sulfonic acid ester salt, with 1 mol of ester base 2 mol the pyrazolone aminomethane sulfonic acid components come.

If one wishes to isolate the solid salt from this solution, one can proceed as follows, for example: that the aqueous solution is evaporated in vacuo and the residue thus obtained with absolute Ethyl alcohol extracted, removing the remaining inorganic salt. When evaporating the alcoholic extract a hard, glass-like, very hygroscopic mass is obtained, which is very easily dissolves in water.

example 1

A solution of 170 g of the sodium salt of 4 - methylamines - 2, 3 - dimethyl -1 - phenyl - pyrazolon- (5) -methane-sulfonic acid- (4) in 200 cm ^{3 of} water is cooled with a solution of 81.5 g aN - (/? - diethylaminoethyl) - aminophenylessigsäureisoamylester in dilute sulfuric acid (25 g concentrated sulfuric acid and 110 cm ³ water), the mixture cooled with ice, the precipitated Na ₂ SO ₄ sucked off and washed twice with 25 cm ³ ice water.

This solution is brought to the desired concentration and adjusted with suitable buffers to the desired _pH value.

Example 2

Claims (1)

PATENT CLAIM: The reaction components are, as described in Example 1, reacted with one another in aqueous solution, the water is removed from the resulting solution in vacuo at the lowest possible temperature and the residue is extracted with absolute alcohol. Then sucked to the undissolved Na ₂ SO ₄ from, the alcoholic extract evaporated in vacuo to dryness, the residue is dissolved again in water, and provides a solution to the desired concentration forth, which is adjusted to the required _pH value. With the 4-methylamino-2, 3-dimethyl-i-phenyl-pyrazolone- (5) -methanesulfonic acid- (4) salt prepared according to the invention of the a-N - (/ 3-diethylaminoethyl) aminophenyl acetic acid isoamyl ester severe cones of the internal organs can be eliminated promptly. This range of indications was practically only up to now reserved for opiates, over whom the preparations of the invention have the advantage that with them the Risk of chronic poisoning, especially the risk of addiction, is excluded. Process for the preparation of a spasmolytically active salt of a-N - (/ S-diethylaminoethyl) aminophenylacetic acid isoamyl ester, characterized in that the a-N - (/ S-diethylaminoethyl) aminophenyl acetic acid isoamyl ester, preferably as a sulfuric acid salt, with 4-methylamino-2, 3-dimethyl -1 - phenyl - pyrazolone - (5) - methanesulfonic acid (4), preferably as the sodium salt, converted to salt formation according to the usual methods will. © 609 709/390 11.56 (709 514 / 1T6 5.57)