DE213155C - - Google Patents

Description

IMPERIAL M

PATENT OFFICE.

PATENT LETTERING

- M 213155 CLASS 12 or GROUP

Patented in the German Empire on August 20, 1907. Longest duration: October 4, 1921.

It has been found that p-aminophenylarsinic acid, its homologues and derivatives are successful in urea and thiourea derivatives of the type:

NH-CO

NH. CS

respectively.

AsO (OHJ ₂

AsO (OH) ₂

convert, where R is an alkyl, aryl or hydrogen. Such compounds are obtained by the action of cyanic acid or sulfocyanic acid or their esters on p-aminophenylarsinic acid and its derivatives. The new compounds are substances that crystallize well and are sparingly soluble in cold water and dilute mineral acids. As a result of the entry of the urea residue, their toxicity is greatly reduced compared to the starting products.

The urea derivatives of phenylarsinic acid are also less toxic than those already known acyl derivatives of p-aminophenylarsinic acid, which property explains them can find in it that the urea derivatives in the organism more difficult to split are subject to than the acyl derivatives.

The 35th result from the following comparative data

Superiority of the new urea derivatives. The toxicity of arsanilic acid is so great that ι ecm of a solution ι: 150 to 20 g of body weight causes death in mice in about 75 percent of all experiments; Acetylarsanilic acid is less toxic, but leads 1 ecm 1:85 each time causes death, while at the same concentration methylcarbaminoarsanilic acid in never had such a result. Methylcarbaminoarsanilic acid is also found in rabbits than half as toxic as acetylarsanilic acid. On the other hand are the healing functions the arsanilic acid in the mouse is relatively low, as with the usual test method (cf. Berlin clinical. Wochenschrift 1907, Chemotherapie, p. 15 of the separate print), in which the Animals tested on the first day after infection achieved only 5 percent healing results became. In contrast, when using urea derivatives, ζ. Β. of Methylurea, possible even on the second day of infection, on which the blood of the Experimental animals riddled with millions of parasites can still achieve healing results, and through a single injection. So it is possible to heal an animal that only a few can Hours from death.

With the acetylatoxyl one can still achieve a cure on the second day, but it is this generally requires the injection to be repeated three to four times, and

Claims (1)

20th 35 40 45 55 then the percentage of cures is lower than with a single methylurea injection. As far as the diarsanilureas mentioned in patent 191548 are concerned, the investigation has shown that the linking of the two arsanilresfe by the C 0 group causes a very significant reduction in toxicity (toxicity like methylurea of arsanilic acid), but this does not result in the healing functions has been increased in a corresponding manner, so that a practical use of the diarsanil urea is far inferior to that of the asymmetrical urea. The manufacturing processes result from the following examples: Example I. Carbaminoarsanilic acid.
620 g of arsanilic acid sodium are dissolved in 3.61 cold water, 480 g of potassium cyanate and, after its dissolution, 480 ecm of glacial acetic acid are added and left to stand for 24 hours at normal temperature. Then it is acidified with 1560 ecm hydrochloric acid (specific weight 1.124) and crystallization is initiated by rubbing the walls of the vessel. After standing for several hours, it is filtered off with suction, washed free of hydrochloric acid with water and dried. Example II. Th i oc ar barn ino arsanilic acid.
To 60 g of potassium rhodium in ^x / ₂ l of water are added 78 ecm of hydrochloric acid (specific weight 1.124) and then arsanilic acid as long as it dissolves (about 83 g). It is now evaporated to dryness on the water bath and the residue is heated in the same way for a further 2 hours. After cooling, it is triturated with 300 ecm of water and 150 ecm of about ten times normal sodium hydroxide solution, the undissolved material is filtered off and the product is poured into excess, dilute hydrochloric acid. Example III. Methylcarbaminoarsanilic acid.
14 g of methyl cyanate are added to 40 g of arsanilic acid sodium, dissolved in 240 g of water, while cooling with ice, and the mixture is then left to stand in the refrigerator for 12 hours. It is then acidified with 52 ecm hydrochloric acid (specific weight 1.12) and allowed to crystallize. Further treatment as in example I. Example IV. Phenyl carbarn ino a rs anilic acid.
18 g of phenyl cyanate are added to 31 g of arsanilic acid sodium in 300 g of water while cooling with ice and the mixture is left to stand for 12 hours at a low temperature with frequent shaking. It is then extracted with ether, the undissolved material is filtered off and the ethereal layer is separated from the aqueous layer. When the latter is acidified with 40 ecm hydrochloric acid (specific weight 1.124 ), the product precipitates and is treated further as in Examples I to III. Another / 3 amount is obtained by extracting the undissolved material with warm water and a little soda, filtering and acidifying. Example V. Carbamino-o-methylarsanilic acid. CH ₃ Λ ^ / ΝΗ -CO-NH ₂ . AsO (OH) / ^ / A dissolution of 57.8 g of the sodium salt of o-toluidinarsinic acid, obtainable by heating of o-toluidine with arsenic acid (see Ber. 41, 1672) 65 g of potassium cyanate and 48 ecm of glacial acetic acid are added to 360 ecm of water; after 24 hours When standing, the product is precipitated by 156 ecm hydrochloric acid (specific weight 1.124). Example VI. Car baminoanthr anil ar sin acid. COOH / NH 'CO-NH ₂ 70 75 80 90 AsO (OH) / 52.4 g of anthranilarsinic acid, which is obtained from the aforementioned o-toluidinarsinic acid can be (see Ber. 41, 933), are doubled in 11 water and 200 ecm sodium hydroxide solution normally dissolved, mixed with 65 g of potassium cyanate and 40 ecm of glacial acetic acid and stand for 24 hours calmly. After this time has elapsed, the urea is reduced by adding 200 ecm of hydrochloric acid (specific weight 1.124) deposited. Ρλτεντ claim: 105 Further development of the manufacturing process protected by patent 191548 of acid derivatives of p-aminophenylarsinic acid, characterized in that for the purpose of producing unsymmetrical Urea and thiourea derivatives of arsanilic acid, its homologues and derivatives, cyanic acid, sulfocyanic acid or their esters on arsanilic acid, their homologues or derivatives for: a "5 can be brought into effect. BEHLIN. PRINTED IN THE REICHSPRUCKEnEI.