DE1570032C - Sulphonylureas, process for their preparation and drug excretion from 1214675 - Google Patents

Description

example 1
Np-chlorobenzenesulfonyl-N-morpholine urea

A solution of 26 g of ethyl p-chlorobenzenesulfonylcarbamate in 120 ml of benzene is mixed with 10 g of N-aminomorpholine. A homogeneous solution is obtained with a weak development of heat. After distilling off the benzene under reduced pressure, the residue is heated for 4 hours at 110 to 13O ⁰ C. After cooling, the product is recrystallized from methanol. Yield 25.5 g of colorless crystals with a melting point of 205 to 208 ^° C.
*) Generic, name door N-Butyl-N'-fp-methylsulfonyD-urea.

3 4

Example 2 N- p -chlorobenzenesulfonyl-N '- ^ o -dimethylmorpholine urea

A mixture of 10 g of N-amino- ^ o-dimethylmor- implemented. After recrystallization from methanol pholine, 20 g ρ - chlorobenzenesulfonylcarbamic acid 5, 8 g of product in the form of colorless crystals of ethyl ester and 50 ml of benzene are obtained according to Example 1. Melting point 192 to 195 ⁰ C.

1 sheet of drawings

Claims (3)

Patent claims: 1. Sulphonylureas of the general formula I. R ¹ SO, -NH-CO-NH-N O I IO R ² in which R ¹ and R ^{2 are} either hydrogen atoms or methyl groups. 2. Process for the preparation of the sulfonylureas of the general formula I, characterized in that that in a known manner ρ - ethyl chlorobenzenesulfonylcarbamate with an aminomorpholine of the general formula II R ¹ H ₂ NN II R ² in which R ¹ and R ² have the meaning given above, at temperatures of 100 to 140 ⁰ C. 3. Medicinal preparation consisting of a sulfonylurea of the general formula I and customary carriers and diluents. 35 The invention relates to sulfonylureas of the general formula I. R ¹ " Cl-f V-SO ₂ -NH-CO-NH-N OI 45 R ² in which R ¹ and R ^{2 are} either hydrogen atoms or methyl groups, and a process for their preparation, which is characterized in that ethyl p-chlorobenzenesulfonylcarbamate with an aminomorpholine of the general formula II R ¹ H ₂ N - NO II R ² 55 60 in which R ¹ and R ^{2 have} the meaning given above, is reacted at temperatures of 100 to 140.degree. The desired product can be prepared by heating N-aminomorpholine or N-amino-2,6-dimethylmorpholine with the alkyl p-chlorobenzenesulfonylcarbamic acid in the presence of either an organic solvent such as benzene or acetone, or of water, or in the absence of any solvent, wherein the heat treatment at 100 to 14O ⁰ C is carried out. The compounds of general formula I are valuable antidiabetic agents. Your effect was with Tolbutamide *) compared. The tests were carried out as follows: Wistar rats that had not been fed for 24 hours were each injected with a compound in an amount of 300 mg / kg iv. Blood glucose was determined 1, 2, 4, 6 and 24 hours after administration of the test compound by enzymatic determination of blood glucose, the rats being fed after the first 6 hours to facilitate the readjustment of the blood glucose value. The decrease in the blood sugar value was always determined in relation to the blood sugar content of the control animals, which was set at 100, in milligram percent. The values given are average values from a group of six test animals. The blood sugar values as a function of time ( were entered in a diagram. The figure shows the effectiveness of N-p-chlorobenzenesulfonyl - 2,6 - dimethylmorpholine urea and N - ρ - chlorobenzenesulfonyl - N '- morpholine urea. As can be seen from the drawing, the morpholine compound according to Example 1 in the first Hour has a stronger effect than tolbutamide, but the duration of the effect is compared to tolbutamide a bit shorter. On the other hand is the 2,6-dimethylmorpholine compound according to Example 2 somewhat weaker in the effect than the morpholine compound according to Example 1, but stronger than tolbutamide. In terms of the duration of the hypoglycemic effect approaches The 2,6-dimethyl derivative is best suited to tolbutamide. The therapeutic progress lies in that the compounds of the invention during the first three hours after administration a have a stronger effect than tolbutamide. The acute toxicity of tolbutamide is 2.5 g / kg. that of the compound according to Example 1 is above 20 g / kg, that of the compound according to Example 2 above (^ half 2.5 g / kg, determined as LD ₅₀ on the mouse perorally. The compounds of general formula I show in tests carried out on mice for more than 75 days who were offered 0.05% solutions of the sodium salt of the compounds for drinking, none chronic symptoms and no growth retardation. The number of erythrocytes and leukocytes in the test animals and a control group, the 0.05% aqueous saline solution for drinking was offered showed no differences.