SU562978A1 - Thiazolidine derivatives possessing antifungus activity and method of obtaining same - Google Patents

Description

There are, and the filtrate is used to reheat the hot extraction of an insoluble precipitate.

23 g (73.2%) of 5,6-dihydropyrrolo 2 are obtained, 1- & thiazolidine-2,3-dione, so pl. 133-135 ° C.

Found,%: C 46.40; H 3.07; N 8.95; S 20.44.

Calculated,%: C 46.42; H 3.24; N 9.05; S 20.67.

Molecular weight confirmed by mass spectrometry.

IR spectrum: (1725 and 1680 CM-i).

PMR spectrum: singlet at b 5.87 ppm. (H – C).

Example 2. 5,6-Dihydro-7H-pyridino 2,1-b thiazolidin-2,3-dione.

In a 0.5 liter flask equipped with a stirrer, a thermometer, a dropping funnel and a chlorine tube, 23 g (0.2 mol) of thiopiperidone-2 and 250 ml of dry chloroform are charged. To the resulting solution at 20-ZO C is added dropwise, vigorously stirring, 25.4 g (0.2 mol) of dichlorohydrogen dichloride, maxionic acid. The reaction mass is stirred for 12 hours at room temperature, evaporated to dryness in vacuum at a temperature not higher than, recrystallized from 100 ml of isopropyl alcohol and dried in vacuum. Obtain 32 g (94.5%) of 5,6-dihydro-7H-pyridino 2,1-d thiazolidin-2,3-dione, m.p. 74-76 ° C.

Found,%: C 50.65; H 4.38; N 8.40; S 17.61.

Calculated,%: C 49.69; H 4.15; N 8.29; S 18.96.

Molecular weight confirmed by mass spectrometry.

IR spectrum: (1720 and 1680 cm-i).

PMR spectrum: singlet at b 5.59 ppm (H – C).

Example 3. 5,6,7,8-Tetrahydroazepino 2.1 - & thiazole idin-2,3-dione.

A 25.8 g (0.02 mol) solution of thiocaprolactam in 300 ml of dry benzene is loaded into a flask equipped with a stirrer, a dropping funnel, a thermometer and a chloro-calcium tube, cooled to 10 ° C and with anti-microbial efficiency of the compounds

26.4 g (0.2 mol) of oxalic acid dichloride is added dropwise to the stirring. The mass is stirred at 10-15 ° C for one hour, the benzene is evaporated in vacuum at a temperature not higher than 50 ° C, the residue is extracted with 500 ml of cinnamon, its diisopropyl ether. The extracts are cooled to -5 ° C, the precipitated crystals are filtered, the filtrate is used to repeat

extraction of the undissolved residue.

26.5 g (72.5%) of 5,6,7,8-tetrahydroazepino 2, 1 are obtained - & thiazolidine - 2,3 - dione, m. pl. 60-62 ° C.

Found,%: C 51.52; H 4.93; N 8.03;

S 17.42.

Calculated,%: C, 52.44; H 4.95; N 7.64; S 17.50.

Molecular weight is confirmed by an esterically mass spectra.

IR: C O (1720 n 1680 cm).

PMR spectrum: singlet at b 5.47 ppm (H – C).

Test antifungal activity. Antimicrobial activity of 5,6-dihydro-7H-pyridino 2, 1-b thiazolidine - 2,2-dione, 5,6,7,8 - tetrahydroazepino 2,1 - b thiazolidin-2, 3-dione and 5,6 - dihydropyrrolo 2 , 1-b thiazolidine-2,3-dione was studied by the method of double serial dilutions in liquid

nutrient medium in relation to 5 types of microorganisms (fungi and bacteria).

Hottiiger broth was used to cultivate the bacteria, and Saburo's medium was used for pathogenic fungi. Microbial load

for bacterial cultures it is 250 thousand cells in 1 ml of nutrient medium, for fungi - 500 thousand reproductive bodies in 1 ml. Cultivated at 28 ° C for 7 days.

The antimicrobial activity of the compounds was assessed by the minimum concentration of the chemical compound required to retard the growth of the microorganism test culture.

The toxicity of the compounds was studied in outbred white mice (18–24 g) by determining the maximum tolerated dose (MTD) after subcutaneous administration in the Sample Table I

symide dimethylsulfoxnd and physiological saline with a life expectancy of G1; for 14 days.

The results of the study of the biological activity of the thiazolidine-2,3-dione derivatives are presented in Table. 1 and 2.

From tab. 1 shows that the derivatives of thiazolidin-2, 3-dione have specific anti-fungal activity against trichophyton - pathogen surface

Antifungal effectiveness of compounds in comparison with known substances

mycoses of humans and animals. At the same time, 5,6-dihydro-7H-iiridino 2, 1-b thiazolidin-2,3-dioi has the most effective effect on pathogenic fungi. This compound is highly active against tri Hofiton and weakly inhibits the growth of bacteria. This substance is non-toxic to animals: the maximally tolerable doses of mice when iodine is more than 1000 mg / kg.

table 2

Claims (2)

1. Derivatives of thiazolidine General formula where n 1 - 4, exhibiting antifungal activity. 2. The method for producing compounds according to claim 1, characterized in that the corresponding tpolactam is identified with oxalic acid dichloride hydride in an organic solvent medium. Sources of information taken into account during the examination 1. Mashkovsky M. D. Medicinal plants. Part 2, M., "Medicine, 1972, p. 406, 316, 313.