SU782337A1 - 2h,4h-2,4-dimethyl-6-amino-1.3,5-dithiazine possessing radioprotective action - Google Patents

Abstract

2H, 4H-2,4-Dimethyl-6-amino-1,3,5dithiazine of formula 1: NHo S with a radioprotective effect.

Description

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The invention relates to new biologically active chemical compounds, namely to 2H, 4H-2, A-dimethyl-6-amino-1,3,5-dithiazine of a formula having a radioprotective effect. This property allows us to assume the possibility use of this compound in medicine. The bis - ((3-amioethyl) disulfide (cystamine) dihydrochloride of the formulas S-CHg-CHg-W S CH 2 CH 2 NH 2 used and known as a substance that protects against radiation is known. The aim of the invention is to expand the product range of compounds exhibiting radioprotective properties. This goal is achieved by a novel compound of formula 1 as a substance having a radioprotective effect. It is obtained by treating the nitrate 2H, 4H-2, A-dimethyl-6-amino-1,3,5dithiazini with a base. Scheme of the process .2 B-SHTOZ, CH5 where B-KOH, 11 (C2H5), As osnoanie; It is possible to use both mineral alkalis, eg caustic potash, and tertiary amines, for example, triethylamine, in an aqueous medium or in an organic solvent medium,. as a diesel ester, with ice-cold 7, release of 1,3,5-dithiazine by filtration in the case of an aqueous medium, or by removing the solvent in vacuo,. In the PMR spectrum of 2H, 4H-2,4-dimethyl-amino-, 3,5-dithiazine, the following are observed: the doublet of the SND groups in the 1.48 and 1.50 ppm regions. and, respectively, two quartets of methin protons of CH-CH3 fragments at 4.49 and 4.66 ppm . (PIR spectra were recorded on a Tesla-BS-487 C spectrometer with a working frequency of 80 MHz, the solvent — CfljOfl internal standard — TMS), a K spectrum of 2H, 4H-2,4-dimethyl-6-amino-1, 3.5- dithiazine contains several maxima in the region of 3000-3400 with corresponding NH vibrations. Intensive absorption at 1600-1655 refers to flat deformation vibrations of NH, and absorption of the C-N bond falls here. In the region of 650-700 cm, stretching vibrations of zi C - S. Methyl is represented by oak - in the summer with frequencies of 1370 - 1450 cm (deformation symmetric and asymmetric oscillations C - H) and absorption in the region of .2870–2960 cm (C – H stretching vibrations). Example 1. Getting 2H, 4H-. 2,4-dimethyl-6-amnno-I, 3,5-dithiazine, To an aqueous solution (80 ml) of nitrate 4H-2,4-dimethyl-6-amino-1,3,5-dithiazini (8 g) at while stirring, 72 ml of 0.5 and KOH solution were added, and the transfer was continued at room temperature for 4 hours. The white precipitate is filtered off, washed 3 with cold water (ml), dried and recrystallized from SCC or ethanol. Get 4, 2 g (73%) of the target product with so pl. 101-102s. Found; C 37.2; H 6.2; N 17.3; S 39.2. CjHjoN S. Calculated: C 37.0; H 6.2; N 17.3; S 39.5%; Example 2. Preparation of 2H, 4H2, 4-dimethyl-6-amino-1,3,5-dithiazine. To a stirred solution of 2H, 4H-2,4-dimethyl-6-amino-1,3,5dithiazini nitrate in 50 MP diethyl ether at room temperature was added 1.35 g of triethylamine. After 6 h, the ethereal solution of 2H, 4H-2,4-dimethyl-amino-1, 3,5-dithiazine is separated by filtration from the precipitate N (CjH5-) a-HCO3. 3 j the precipitate is washed 3 times with ether (Ie combined ether solutions remove e4) ir in vacuo. The obtained target product is recrystallized from CC14. I get 1.5 g (70%) of 2H, 4H-2,4-dimethyl-6-amine-, 3,5 dithiazine with m.p. 02-103C. 2H, 4H2, 4-dimethyl-6-amino-1,3,5-dithiazine stable colorless Kristagschik substance, soluble in alcohols, chloroform, carbon tetrachloride, ether, benzene, acetone and dimethylsulfoxidio Example 3. Tests 2H, 4H2, 4- dimethyl-6-amino-1,3,5-dithiazine for toxicity and radi-protective properties. When testing for the biological activity of 2H, 4n-2,4gdimethyl-6-amino-1, 3,5-dithiazine, it was found that this compound has a pronounced radioprotective effect. The experiments were carried out on 105 men of the F CBAjCj BT male line weighing 18 - 22 g. The radioprotective properties of 2H, 4n-2,4-dimethyl-6-amino-1, 3-5-dithiazine were studied with a single total external gamma irradiation at a dose of 950 r at power source 70 p / min. The compound was administered intraperitoneally once in doses of I / 2 and 1/8 of DM 4 10 minutes before radiation exposure. The radiosylt efficacy of the compound versus cistart was evaluated by the percentage of surviving animals during the DL days after irradiation (minus the results of the control experiment) and the value of the sacrificial index. , Acute toxicity was studied1 when administered intraperitoneally, showed diabetes, diabetes mellitus 50 f m, diabetes 84 was calculated by probitolysis according to Litchfield and Wilcoxon. The compound of formula 1 was introduced in the form of a freshly prepared stone oil solution with dimethyl sulfoxide (10%). Research has established that a compound of the formula is a biologically active compound. Toxicity after intraperitoneal administration. According to the indicator, SDU is 77.5 mg / kg, in which dose in the poisoning picture 374 symptoms of central nervous system excitation were observed. With intravenous administration in doses of 8 and 33 mg / kg, corresponding to 1/8 and 1/2 DM, 2H, 4I2, 4-dimethyl-6-amino-1,3,5-dithiazine showed a pronounced radioprotective activity equal to 50 and 40%. In these doses, the compound was well tolerated by animals and did not have any side effects. The tread index for the test compound is 14.53 and 3.29, respectively. Radiation protective effect of 2Hv, 4H-2,4-dimethyl-6-amino-1,3,5 dithiazomas was performed with cystamine (mg / kg), which, under these experimental conditions, was administered at a dose of 38 mg / kg (1 / 8 SD) protected against the death of 17% of mice. In the optimal radioprotective dose (|; Ё5 mg / kg), the survival rate increased by 32% under the influence of cystamine, but when this happened, there were side effects (depression, decrease in motor activity). The protector for cystamine in our studies was 2.1. The test results are presented in Tables 1 and 2. From the test results it can be seen that the compound of general formula 1 is a biologically active substance that has a pronounced radioprotective effect (50 - 40%) with rynutriboritinny introduction (1/8 and 1/2) before irradiation (60 Co, 950 r, 70 p / min). Unlike cystamine in 2H, 4H2, 4-dime gs1-6-amino-1,3,5-dithiazine, the value of the protector of the Ro index is 6.9 I f times higher in radioprotective, there are no side effects. Table 1 Toxicity of 2H, 4H-2,4-dimesh1-6-amino1, 3,5-dithiazine for mice with intraperitoneal administration, toxicity, mg / kg 77.5f2.8

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The radioacoustic properties of 2H, AN-2,4-dimethyl-amno-1, 3.5, h1giazine, when administered to mice up to a single dose of it in the current gamma-ray, were given at a dose of 95Q r with a dose of 70 p / min.

Table 2

Claims (1)

2H, 4H-2,4-Dimethyl-6-amino-1,3,5dithiazine of the formula 1: ‘ ΝΗο 1CC 8 CH ₃ having a radioprotective effect. OS No. CO with -h 1,782337 2