PL133952B2 - Process for preparing novel 5-/-p-hydroxybenzylideneimino/-3-methylisothiazolo-/5,4-d-pyrimidin/7h/-4,6-dione - Google Patents

Description

The subject of the invention is a process for the preparation of a new 5,4-d) -pyrimidine (7H) -4,6-dione 5- (p-hydroxybenase lidenoimino) -3-methyl-isothiazole of the formula 1. Antitumor properties, which was found on the basis of studies conducted on experimental animals. According to the research, the compound of formula 1, used in doses of 0.1 LD50, inhibits the development of L 1210 leukemia and B 16 melanoma. Effectiveness of using a new compound of formula 1 was confirmed by in vivo tests on CDF1 mice which were intraperitoneally transplanted with 105 leukemic cells. The use of the compound of formula 1 resulted in an increase in the survival state by about 80% compared to the control animals. Very high activity was shown by the compound of the formula 1 in the B16 melanoma system, resulting in an increase in survival time by over 100%, in this case studies were carried out on BDE mice, which had been transplanted intraperitoneally or subcutaneously with 0.25 ml of homogenate made of B16 melanoma gases. At the same time, the compound of formula I, in contrast to most of the anti-cancer drugs used, shows a relatively low toxicity. The toxic substance of formula I determined by the Lichtfild and Wilcoxon method is: LD50-387 mgAg for intraperitoneal administration and 1360 mg / kg for oral administration. In the light of the comparative studies of the compound of formula 1, the effectiveness of action is equal to that of fluorouracil, while showing at the same time several times less toxicity. The method according to the invention consists in the fact that 5-amino-3-methyl-isothiazole / 5.4 pyrimidine / 7H / -4 The 6-dione of formula 2, obtained by the method according to the Polish patent specification No. 114192, is reacted with p-hydroxybenzoic aldehyde in an anhydrous ethyl alcohol environment at boiling temperature. The method according to the invention is presented in the example of the embodiment. 2 133952 Example . 7.5 g of p-hydroxybenzaldehyde are added to a suspension of 5 g of 5-amino-3-methyl-isothiazole (5,4-d) -pyrimidine (7H) 4,6-dione in 125 ml of anhydrous ethanol, and 7.5 g of p-hydroxybenzaldehyde are added and the mixture is stirred. it is heated by keeping it at the boil for 15 hours. Then, after cooling the reaction mixture, 5.5 g of 5- (p-hydroxybenzylideneimino) -3-methyl-isothiazole- (5,4-d) -pyrimidine (7h H -4,6-dione) is filtered off which is crystallized from pyridine by a known method. (As a result: 5- (p-hydroxybenzylideneimino) -3-methyl-isothiazole- (5, <* - d) - pyrimidine- (7H) -4,6-dione, mp 278-280 ° C with yield 68.5%. Patent claim A method for producing a new 5- (p-hydroxybenzylideneimino) -3-methyl-isothiazol- (5,4-d) -pyrimidine (7H) -4,6-dione of formula 1, characterized by in that the 5-amino-3-methylisothiazole (5,4-d) -pyrimidine (7H) -4,6-dione of formula II is heated in dry ethanol with p-hydroxybenzaldehyde to the boiling point of ethanol. H, C / \ NN = CH- ^ O / "0H vAA pattern ¦r \ H, C 0 II NH, \ / \ / \ pattern Sr 2 Printing workshop of the Polish People's Republic. NaJclad 100 Price PLN 100 PL

Claims (6)

1. Patent claim 2. The method of producing new 5- (p-hydroxybenzylideneimino) - 3.- methyl-isothiazol- / 5, 4. -d / - pyrimidine (7H) -4,6-dione of the formula I, characterized by 5.-amino-3-methyl-isothiazole- (5,4-d) - pyrimidine- (7H) -4, The 6-dione of formula II is heated in dry ethanol with p-hydroxybenzaldehyde to the boiling point of ethanol. <H, C / \ N-N = CH- ^ O / "0H vAA pattern ¦r \ H, C 0 II NH, \ / \ / \ pattern Sr 2 Printing House of the PRL. NaJclad 100 Price PLN 100 PL