DE1445140C - Square brackets on 2,6-dimethylpiperidyl- (l) square brackets on -3-sulfamyl-4-chlorobenzoic acid amide, its acid addition salts and processes for their preparation - Google Patents

Description

The invention relates to N - [2,6 - dimethyl - piperidyl- (I)] - 3-sulfamyl-4-chlorobenzoic acid amide of formula I.

its acid addition salts and a process for their production, which is characterized in that that a 3-sulfamyl-4-chlorobenzoyl halide of the general formula II

Sodiumureticum and Chlorureticum, being door its It is particularly important for therapeutic use that its effect also after oral administration entry; Its good tolerance should also be emphasized. Because of its specific saluretic The effect is said to be the N- [cis-2,6-dimethylpiperidyl - (1)] - 3 - sulfamyl - 4 - chlorobenzoic acid amide particularly valuable from a therapeutic point of view. To demonstrate the superior diuretic effect the cis and trans form of the compound of formula I were comparative experiments with the known o-chloro-T-sulfamyl-S ^ -dihydro-l ^^ - benzothiadiazine-l, l-dioxide carried out, the results of which are summarized in the following table:

'5.

SO ₂ - NH,

(ID

co-x

in which X is a chlorine or bromine atom, with l-amino-2,6-dimethylpiperidine of the formula III

H, N - N

substance 20th N- [cis-2,6-dimethyl-
piperidyl- (l)] - 3-suIf-
amyI-4-chlorobenzoe-
acid amide Diuretic
Effect at
mg / kg p. 0. Acute
Toxicity in
mg'kg iv N- [trans-2,6-dimethyl-
piperidyl- (l)] - 3-sulf-
amyl-4-chlorobenzoe-
acid amide ED ₅₀ DL ₅₀ 30 6-chloro-7-sulfamyl-3,4-di-
hydro-1,2,4-benzo-
thiadiazine-1,1-dioxide 0.01 500 0.05 > 2'50 0.1 > 350

(III)

CH ₁

reacted in a manner known per se and optionally converting the compound thus obtained into an acid addition salt convicted.

The implementation of the S-sulfamyl ^ chlorobenzoyl halides with the 1-amino-2,6-dimethyl-piperidine is preferably carried out in an organic solvent which is inert under the reaction conditions, e.g. B. in a halogenated hydrocarbon such as chloroform; the implementation can also be done in the absence a solvent can be made. The hydrogen halide released during the reaction can increase the response time and / or the Reduce yield. It is therefore advantageous, although not essential for the reaction to succeed necessary to add an acid-binding agent, for example a tertiary one, to the reaction mixture organic base such as triethylamine.

A preferred embodiment of the manufacturing process is as follows: The suspension of the 1-amino-2,6-dimethyl-piperidine or one of its Acid addition salts in chloroform are mixed with triethylamine. This is followed by a 3-sulfamyl-4-chlorobenzoyl halide added and stirred for 24 to 100 hours at room temperature. Subsequently the reaction mixture is worked up in a known manner and, if necessary, purified.

N- [2,6-Dimethyl-piperidyl- (I)] -3-sulfamyl-4-chlorobenzoic acid amide is characterized by interesting, therapeutically utilizable pharmacodynamic properties. It is suitable as a diuretic, The compound of the formula I or its physiologically tolerable acid addition salts can be used as medicaments be administered alone or in a suitable drug form with pharmacologically inert auxiliaries. In the following examples, which explain the invention in more detail, all temperature data are given in degrees Celsius and are uncorrected.

example 1

N- [cis-2,6-DimethyI-piperidyI- (1)] -3-sulfamyl-4-chlorobenzoic acid amide

A solution of 3.8 g of 1-amino-cis ^ o-dimethylpiperidine and 3.0 g of triethylamine in 150 ml of chloroform is stirred at 20 to 25 ° C within of 20 minutes with 7.6 g of S-sulfamyM-chlorobenzoyl chloride added and the yellow reaction solution then continued for 48 hours at room temperature.

55 stirred. It is then evaporated to dryness in a vacuum, the residue taken up in 200 ml of ethyl acetate and repeated several times with a total of Washed 200 ml of water. After drying over magnesium sulfate, the ethyl acetate is im Distilled off in vacuo and the residue on aluminum oxide chromatography «, the N- [cis-2,6-DimethyI-piperidyl- (l)] -3-sulfamyl-4-chlorobenzoic acid amide with a mixed solvent of chloroform and methanol (9: 1) is eluted. After recrystallization from methanol-diisopropyl ether, the melts Connect at 233 to 235 ° C. Yield 68%. After further purification, a product that melts at 244 to 245 ° C becomes Material received.

Example 2

. N- [trans-2,6-Dimethyl-piperidyl- (1)] -3-sulfamyl-4-chlorobenzoic acid amide

A solution of 3.8 g of l-amino-trans-2,6-dimethylpiperidine and 3.0 g of triethylamine in 150 ml of chloroform is stirred at 20 to 25 ° C within 20 minutes with 7.6 g of 3-sulfamyl 4-chloro-benzoyl chloride is added and the yellow reaction solution is then stirred for a further 100 hours at room temperature. It is then evaporated to dryness in vacuo, the residue is taken up in 200 ml of ethyl acetate and washed several times with a total of 100 ml of water. After drying over magnesium sulfate, the ethyl acetate is distilled off in vacuo and the residue is chromatographed over aluminum oxide, the N- [trans-2,6-dimethyl-piperidyl- (1)] -3-sulfamyl-4-chlorobenzoic acid amide with a chloroform-methanol solvent mixture (9: 1) is eluted. After recrystallization from methanol-chloroform, the compound melts at 234 ^° C. Yield 32%.

The mixed melting point with N- ^{[cis-2,6-dimethyl-:} piperidyl - (1)] - 3 - sulfamyl - 4 - chlorbenzoesäureamid (F. 244-245 ° C) shows a depression at 225-227 ⁰ C. ·

Claims (2)

Patent claims: 1. N - [2,6 - Dimethylpiperidyl - (I)] - 3 - sulfamyl-4-chlorobenzoic acid amide and its acid addition salts. 30th 2. Process for the preparation of the compounds according to claim 1, characterized in that a 3-sulfamyl-4-chlorobenzoyl halide of the general formula II SO ₇ NH, αϊ) in which X is a chlorine or bromine atom, with l-amino-2,6-dimethyl-piperidine of the formula III CH H ₇ NN (III) reacted in a manner known per se and optionally converting the compound thus obtained into an acid addition salt convicted.