DE1817958C3 - Molecular compounds from aminoethanesulfonyl-p-phenetidine and barbituric acids - Google Patents

Description

Moles of II barbitals and their moles

• Melting point of the product

The present invention relates to molecular compounds of 2 mol aminoethanesulfonyl-p-phenetidine (H) and one mole of a barbituric acid obtained by reacting II with a barbituric acid

NH ₂ (CH ₂ I ₂ SO ₂ NH-

(H)

II, which is used as a starting material, is so far unpublished and therefore a novel compound that z. B. can be prepared by hydrolysis of Acylaminoäthansulfonylp-phenetidine. II contains the structural features of p-phenetidine, which has an analgesic effect and also has one Antipyreticum represents, and of taurine, an essential amino acid with surface-active effect.

The compound of formula II can be used as a very stable, water-soluble antipyretic with very low toxicity. The molecular compounds according to the invention also show excellent analgesic and antipyretic effects.

Barbituric acids that can be used according to the invention are, for example:

Barbital (5,5-diethylbarbituric acid), Allobarbital (5,5-diallylbarbituric acid), Cyclobarbital

(5- [1 -Cyclohexenyl] -5-ethyl-barbituric acid),

Phenobarbital (5-ethyl-5-phenylbarbituric acid), Apbarbital (5-allyl-5-isopropylbarbituric acid), Amobarbital (5-ethyl-5-isoamylbarbituric acid), Pentobarbital

(5-ethyl-5- (1-methylbutyl) barbituric acid),

Secobarbital

(5-allyl-5- (1-methylbutyl) barbituric acid),

Vinbarbital

(5-ethyl-5- (1 -methyl-1-butenyl) barbituric acid),

Butabarbital (5-ethyl-5-sec-butylbarbituric acid)

and

Mephobarbital

(5-ethyl-1-methyl-5-phenylbarbituric acid).

35

40

45

55

6o

To prepare the molecular compounds according to the invention you can, for. B. the compound of formula II Mix with an appropriate barbituric acid and heat this mixture to melt or II with a barbituric acid in water, methanol, ethanol or another organic solvent or a 6 $ React mixture of these while heating. When using water as the reactant the yield is particularly good.

1 Mole Barbital, 1 mole 123 to 139 2 Mole desgL the same 123 to 140 3 Mole desgL the same 125 to 140 0.5 Mo! the same the same 124 to 140 1 Mole Allobarbital, 1 month 128 to 132 2 Mole the same the same 128 to 132 3 Mot the same the same 127 to 132 0.5 Mole the same the same 128 to 131 1 Mole Cyclobarbital, 1 mole 124 to 128 2 Mole the same the same 125 to 128 3 Mole the same the same 125 to 127 0.5 Mole the same the same 124 to 128 1 Mot Secobarbital, 1 mole 130 to 142 2 Mole the same the same 130 to 142 3 Mole the same the same 131 to 141 0.5 Mole the same the same 130 to 141

The deposited crystals are dried to constant weight in a dryer. Subsequently, II was determined according to the method described below. The barbituric acids were determined according to the method described in the official Japanese pharmacopoeia. The results of the Determinations showed that molecular compounds were always formed from 1 mole of barbituric acid and 2 moles of II was.

The determination of II was made in the following manner: The sample containing II was dissolved and made a final volume of 1.5 ml. To this was added 2 ml of 2,4-dinitrofluorobenzene reagent added (produced by thoroughly mixing 0.1 g of commercially available 2,4-dinitrofluorobenzene, guaranteed quality, with water up to a volume of 1000 ml and by separating out what is floating above). The mixture was left on for exactly 5 minutes heated a boiling water bath, then immediately chilled in ice water for 5 minutes 0.5 ml of 99.5% strength Ethanol added, and for absorption at 410 πιμ the product valued Separately, instead of the sample solution, 13 ml of water were added using a similar procedure and the absorbance value was taken to be zero. The color produced in the process (yellow) was very stable, but for safety reasons the estimate was made within 5 minutes of the Color reaction made. This color followed Beer’s law when diluted (below 400 mg / ml of salary II).

To further explain the preparation of the compounds according to the invention are given below given some examples.

example 1

Molecular compound from aminoethanesulfonyl-ppheaetidine and barbital (5,5-diethylbarbituric acid)

5 g aminoethanesulfonyl-p-phenetidine and 2 g barbital were dissolved in the smallest possible amount of water and the solution concentrated over a direct flame until oil separated. When the mixture was filtered and allowed to stand, colorless crystals were obtained. Yield 5g. The product was soft part at 123 ° C and melted completely at 140 ⁰ C

Elemental analysis (2
Calculated: N 12.49%;
found: N 12.45%.

Example 2

Molecular compound from aminoethanesulfonyl-pphenetidine and allobarbitaI (5,5-dialylbarbituric acid)

2.4 g of aminoethanesulfonyl-p-phenetidine and 2.1 g Allobarbital were dissolved in the least possible amount of water and heated over free Flame focused. It was then filtered and left to stand. Colorless needles were obtained, melting point 128 to 132 ° C, yield 2 g.

Elemental analysis (2 CioHi6S03N2) (CioHi203N2)
Calculated: N 12.06%;
found: N 12.09%.

Example 3

Molecular compound of aminoethanesulfonyl-p-pheneti-

din and cyclobarbital (5- [I-cyclohexenyl] -5-ethyl-barbi-

turic acid)

3 g of aminoethanesulfonyl-p-phenetidine and 1.5 g of cyclobarbital were dissolved in the smallest possible amount of water and the solution was _{heated to concentrate over a direct flame at 4C} until oil separated out. It was then filtered and left to stand. Colorless needles separated out. Melting point 125 to 128 ° C, yield 3 g.

Elemental analysis (2 · CioHi6S03N2) (Ci2Hi603N2): Calculated: N 11.59%;
found: N 11.63%.

Example 4

Molecular compound from aminoethanesulfonyl-p-phenetidine and secobarbital (5-allyl-5- {l-methylbutyl) -bar-

bituric acid)

J β g of secobarbital and 3 g of aminoethanesulfonyl-p-phenetidine were dissolved in the smallest possible amount of water. The solution was heated over a free flame to concentrate, then filtered while it was warm and the filtrate was allowed to stand to separate colorless needles, melting point 130 to 142 ° C, yield 3 g.

Elemental analysis (2 · CioHi6S03N2) (Ci2Ht803N2): Calculated: N 11.56%;
found: N

3 °

35 To demonstrate the progressive properties of the molecular compounds according to the invention, the analgesic effect was tested with the aid of the Haffner method in comparison to the standard compound phenacetin. Male mice of the "dd-K-pure strain" (12 g body weight) were used as test animals. J.7 10 mice were used as one group in the test. The following table shows the result:

Checked Appli- LDso / EDüo mg / kg) Therap. links cationic index art (both 700 (= LDüo / 200 EDso) Phenacetin p. O. 3100 4.43 connection of p.o. 1300 250 6.5 example 1 connection of p. O. 1900 100 7.2 Example 2 connection of p.o. 690 100 6.9 Example 3 connection of p.o. 600 6.0 Example 4

Claims (3)

Patent claims: 1. Molecular compounds consisting of 2 moles Aminoethanesulfonyl-p-phenetidine and one mole of a barbituric acid. 2. Process for the preparation of the molecular compound according to claim 1, characterized in that Aminoethanesulfonyl-p-phenetidine is reacted with a barbituric acid in a manner known per se 3. Medicament, characterized in that it consists of a molecular compound according to claim 1 and customary auxiliaries and carriers The molecular compounds thus obtained are stable crystals with constant melting points, even if the molar ratio of Ii to the barbituric acids was varied; the determination of the composition showed that the crystalline products consisted of two moles of II and one mole of barbituric acid. Another Explanation of the manufacturing process is as follows: II and the corresponding barbituric acid are dissolved in water in various molar ratios concentrated in a direct flame, filtered and left to stand for the crystals to separate out. The carried out Responses are shown in the table below: