RU2650516C1 - Synthesis of new 2-mercaptobenztellurazole derivatives with biological activity - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to new 2-mercaptobenztellurazole derivatives having structural formula

.

EFFECT: compounds have biological activity, namely they have ability to reduce content of thiol groups in blood plasma and glucose content, which makes it possible to use them for controlling rodents.

1 cl, 1 tbl, 6 ex

Description

The invention relates to the field of chemistry of heterocyclic compounds, and in particular to a method for producing derivatives of 2-mercaptobenzotelllurazole - substances with a biologically active effect.

Alkylation of 2-mercaptobenzimidazole, -oxazole and -thiazole with various halogen derivatives is carried out in the presence of a base (KOH, K ₂ CO ₃ , NaOMe, pyridine) in such solvents as water, ethanol, acetone (1. Synthesis, antioxidant properties and radioprotective effects of new benzothiazoles and thiadiazoles / D. Cressier, C. Prouillac, P. Hernandez et al. // Bioorganic & Medicinal Chemistry. - 2009. - No. 7. - P. 5275-5284. 2. New anticandidous 2-alkylthio-6-aminobenzothiazoles / E. Sidoova, D. Loos, H. Bujdakova, J. Kallova // Molecules. - 1997. - No. 2. - P. 36-42. 3. Huang, W. Microwave-assisted one-pot synthesis and fungicidal activity of polyfluorinated 2-benzylthiobenzothiazoles / W. Huang, GF Yang. // Bioorg. Med. Chem. - 2006. - No. 14. - P. 8280-8285. 4. Organic reactions in ionic liquids: an efficient method for select ive s-alkylation of 2-mercaptobenzothia (oxa) zole with alkyl halides / Y. Hu, ZC Chen, ZG Le, QG Zheng // Synth. Commun. - 2004. - Vol. 34, No. 11. - P. 2039- 2046. 5. Ultrasound promoted synthesis of thioesters from 2-mercaptobenzoxa (thia) zoles / A. Duarte, W. Cunico, CMP Pereira et al. // Ultrason. Sonochem. - 2010 .-- Vol. 17. - P. 281-283. 6. Dalai, DS Synthesis of 2-mercaptobenzothiazole and of 2-mercaptobenzimidazole derivativesusing polimer-supported anions / DS Dalai, NS Pawar, PP Mahulikar // Organic Preparations and Procedures Int. - 2005. - Vol. 37, No. 6. - P. 539-546. 7. An easy and fast ultrasonic selective S-alkylation of hetarylthiols at room temperature / T. Deligeorgiev, S. Kaloyanova, N. Lesev, Juan J. Vaquero // Ultrason. Sonochem. - 2010 .-- Vol. 17. - P. 783-788. 8. Thiazole orange derivatives: synthesis, fluorescence properties, and labeling cancer cells / X. Fei, Y. Gu, Y. Ban et al. // Bioorg. Med. Chem. - 2009. - Vol. 17. - P. 585-591. 9. U.S. Patent 48244645, 1990, H. Turn, N. Eiki, S. Ryo, M. Konichi. 10. U.S. Patent 3901909, 1976, NY Lakashmi, HR Dieter. 11. Application. No. 63-208579 Japan 1990, O. Susumu, S. Katsu, Y. Tomio, N. Yutaka, X. Masatoshi. "Derivatives of benzimidazole, their preparation and antiulcer drugs based on them." 12. US Patent 5091399, 1993, Osei-Gyimah, SE Sherba, Rohmm Haas).

In recent years, more and more attention of researchers has been attracted by hetaryloxy (amino, thio) acetic acids and their functional derivatives, since among them substances with high biological activity and useful applied properties have been found.

A known method of producing (1H-Benzothiazol-2-yl-thio) acetic acid and ethyl (1,3-benzothiazol-2-yl-sulfanyl) acetate by heating and stirring for 1 h by reaction with ether and bromo or chloroacetic acid in anhydrous acetone in the presence of K ₂ CO ₃ or KOH described in (DeshmukhSU, Zaheeruddin, RajeevaB, ShantakumarSM, PuttaRajeshKumar. Synthesis, Chemical Characterization and Antimicrobial Activity of Some Novel Benzimidazole Derivatives. // Journal of Biomedical and Pharmaceutical Research 1 (3) 126-133, Chetna A, Diwaker S, Rajat A „and Suresh CA // Indo. J. Chem., 2010, 10. (3), P. 376-381., V. Mohan Goud, N. Sreenivasulul, Avanapu Srinivasa Rao and Srinivas Chigiri. Synthesis, antimicrobial and pharmacological evaluation of substituted novel benzimida zoles // Der Pharma Chemica, 2011, 3. (1), 446-452., Ashish L. Asrondkar, Vrushali N. Patil, Anil S. Bobade and Abhay S. Chowdhary // Der Pharma Chemica, 2015, 7. ( 4) P. 225)

,

,

The authors of the work (TG Deligeorgiev, A.A. Kurutos, NI Gadjev, AA Alexiev. An easy and fast one-pot preparation of 2-thiomethyl and 2-thioacyl benzothiazoles, benzoxazoles, and benzimidazoles. // Bulgarian Chemical Communications, 2015. Vol. 47. No. 4. p. 1034-1038) 2-benzoyl mercaptobesothiazole, β-imidazole and β-oxazole were synthesized using ultrasonic irradiation of benzoyl chloride with sulfides for 5 min under mild conditions at room temperature with good yields of 85-95%.

, X=NH, S, О

, X = NH, S, O

2-r-Nitrobenzoyl mercaptobenzoimidazole was obtained by the authors (Mahasin F. Alias, Doaa H. Mahal. Synthesis, Structural Diagnosis, Theoretical Treatment and Antibacterial Study of Pd (II), Rh (III), Pt (IV) and Au (III) Complexes Containing 2- (P-NitroBenzoyl) ThioBenzimidazole. // International Journal of Science and Research (IJSR). 2015. (7) Vol. 4 I. 7. p. 1469-1476) by boiling for 4 hours the reaction mixture of 2-mercaptobenzoimidazole and p-nitrobenzoyl chloride in ethyl alcohol in the presence of sodium carbonate, with a yield of 69%.

As is known, under the conditions of basic catalysis, azolin-2-thions react as an ambident anion and, depending on the conditions and structure of the reagents, give S- or N-derivatives.

, Dominique Lorcy, Ivan Leban, Alenka Majcen-Le

. A novel approach to n, n'-dimethyl and n, n'-ethylene bridged dibenzodithiadiazafulvalene // ActaChim. Slov. 2002. Vol. 49. P. 871-883).A known method of producing 2,2 '[ethane-1,2-diylbis (thio)] bis-1,3-benzthiazole and 3- [2- (1,3-benzthiazol-2-ylthio) ethyl] -1,3- benzthiazole-2 (3H) -thione in the interaction of 2-mercaptobenzothiazole with 1,2-dibromethane in the presence of potassium carbonate with yields of 70 and 12%, respectively (

, Dominique Lorcy, Ivan Leban, Alenka Majcen-Le

. A novel approach to n, n'-dimethyl and n, n'-ethylene bridged dibenzodithiadiazafulvalene // ActaChim. Slov. 2002. Vol. 49. P. 871-883).

However, all of the above methods for the preparation of 2-mercaptobenztellurazole derivatives can only be used in a modified form.

Previously, we synthesized 2-mercaptobenztellurazole, which is the starting material (patent RU 2546674 C2, 04/10/2015), and derivatives of 2-mercaptobetzelllurazole, which are close analogues for the claimed compounds (patent RU 2602499 C1, 2016) (Federal State Budgetary Educational Institution) Higher professional education “DAGESTAN STATE UNIVERSITY”) Ali A.A.M., Ramazanova R.A., Abakarov G.M., Tarakanova A.V., AnisimovA.V. // Russ. J. Gen. Chem. 2015. Vol. 85. No 3. P. 722. [Ali A.A.M., Ramazanova P.A., Abakarov G.M., Tarakanova A.V., Anisimov A.V. // JOK. 2015.V. 85. No 3. P. 570.] Ali A.A.M., Ramazanova R.A., Abakarov G.M., Tarakanova A.V., Anisimov A.V. // Russ. J. Gen. Chem. 2016. Vol. 86. No. 4. P. 830. [Ali A.A.M., Ramazanova P.A., Abakarov G.M., Tarakanova A.V., Anisimov A.V. // JOK. 2016. T. 86. No 4. P. 643]

The task is the synthesis of new heterocyclic compounds with a biologically active effect, as well as the search for biologically active substances among nitrogen-containing heterocyclic tellurium compounds.

The technical result consists in the development of methods for the synthesis of new biologically active derivatives of the class mercaptobenztellurazoles.

The essence of the invention is that synthesized new derivatives of 2-mercaptobenztellurazole having the structural formula

the method of obtaining derivatives of 2-mercaptobenztellurazole with biological activity was developed by us and described in Patent No. 2602499 of 10.25.2016, and includes the interaction of 2-mercaptobenztellurazole sodium with the corresponding halides with stirring from 1 to 5 hours.

Thus, we synthesized 6 new derivatives of 2-mercaptobenztellurazole:

1. (1,3-Benztellurazol-2-ylthio) acetic acid (substance 1);

2. Ethyl (1, 3-benztellurazol-2-ylthio) acetate (substance 2);

3. S- (1,3-Benztellurazol-2-yl) thiophene-2-carbotioate (substance 3);

4. S- (1,3-Benztellurazol-2-yl) benzenecarbothioate (substance 4);

5. S- (1,3-Benztellurazol-2-yl) -4-nitrobenzenecarbothioate (substance 5);

6. S- (l, 3-Benztellurazol-2-yl) (2-thioxo-1,3-benztelllurazol-3-yl) ethanethioate (substance 6).

(1,3-Benztellurazol-2-ylthio) acetic acid obtained by reaction of sodium ethylate with α-chloroacetic acid has the structural formula

The synthesis of (1,3-benztellurazol-2-ylthio) acetic acid consists in adding 2-mercaptobenztellurazole to the sodium ethylate solution in small portions while stirring, then adding a solution of α-chloroacetic acid in absolute ethanol. The mixture is stirred at a temperature of 50-60 ° C for 2 hours and for 2 hours at room temperature. The reaction is monitored by TLC, the precipitate formed is filtered off, washed with ethanol, dried and recrystallized.

Example 1

Sodium ethylate obtained from 0.18 g (7.6 mmol) of Na and 25 ml of absolute ethanol was placed in a three-necked flask equipped with a stirrer, a refrigerator, and a dropping funnel. To the resulting sodium ethylate solution, 2 g (4 mmol) of 2-mercaptobenztellurazole was added in small portions over 30 minutes at 30 ° C, then 0.72 g (7.6 mmol) of α-chloroacetic acid in 15 ml of absolute ethanol was added to the reaction mixture. The mixture was stirred at a temperature of 55-60 ° C for 2 hours and for 2 hours at room temperature. The reaction was monitored by TLC, the precipitate formed was filtered off, washed with ethanol, dried in air and recrystallized from tetrahydrofuran. Yield 1.13 g (87%), brown crystals, mp. 242-243 ° C. IR spectrum, ν, cm ^-1 : 3452, 3107, 3066 (ОН), 2961, 2897 (-CH ₂ ), 1754, 1697 (С = O), 1653, 1635 (N = C), 1497, 1452, 1424 (N = C in the loop), 1117, 1080, 742 (CN), 671, 654, 610, 537, 463 (CS). ¹ H NMR spectrum, ppm: 11.48 s (1Н, СН ¹² ), 7.93 d (1Н, СН ⁷ , J 5.7 Hz), 7.25 m (СН ⁴ , 1Н), 7.18-7.10 d (1Н, СН ⁶ ), 7.01-6.73 m (1H, CH ⁵ ), 3.04 m (2H, CH ¹¹ ). ¹³ C NMR spectrum, δ _s , ppm: 170.80 (C ¹² ), 168.91 (C ² ), 127.96 (C ⁹ ), 123.80 (C ⁵ ), 60.21 (C ⁷ ), 45.48 (C ⁴ ), 40.62 (C ⁶ ), 36.92 (C ⁸ ), 21.22 (C ¹¹ ). Mass spectrum, m / z (Irel,%): 290 (100), 264 (96), 2134 (86), 305 (32). Found,%: C 33.73; H 2.27; N, 4.43; S 10.03; Those are 39.81. C ₉ H ₇ NSO ₂ Te. Calculated,%: C 33.69; H 2.20; N, 4.37; S 9.99, Te 39.77.

Ethyl (1,3-benztellurazol-2-ylthio) acetate obtained by reacting 2-methylmercaptobenztellurazole with α-chloroacetic acid ethyl ester in sodium ethylate has the structural formula

Example 2

Sodium ethylate obtained from 0.18 g (7.6 mmol) of Na and 25 ml of absolute ethanol was placed in a three-necked flask equipped with a stirrer, a refrigerator, and a dropping funnel. To the resulting sodium ethylate solution, 2 g (4 mmol) of 2-mercaptobenztellurazole were added in small portions over 30 minutes at 30 ° C, then 0.93 g (0.96 ml, 7.6 mmol) of α-chloroacetic acid ethyl ester was added to the reaction mixture. 15 ml of absolute ethanol. After 15 minutes of stirring, a precipitate begins to precipitate, the mixture was stirred for another 1 h at room temperature. The precipitate was filtered off, washed with ethanol, dried in air and recrystallized from tetrahydrofuran. Yield 1.76 g (66%), orange crystals, mp. 229-231 ° C. IR spectrum, ν, cm ^-1 : 3452, 3107, 3066 (С-Н), 2961, 2897 (-СН ₂ ), 1754, 1735, 1697 (С = O), 1653, 1635 (N = C), 1497, 1542, 1424 (N = C in the cycle), 1117 (С-О-С), 1080, 742 (CN), 671, 654, 610, 537, 463 (CS). ¹ H NMR, δ, ppm .: (1H, ⁵ CH), 4.15 m (2H, -SCH _2), 4.14 d (2H, OCH _2, J 7.1 Hz), 1.21 s (3H, _CH3) . ¹³ C NMR spectrum, δ _c , ppm: 168.51 (C ¹² ), 164.54 (C ² ), 159.35 (C ⁹ ), 133.78 (C ⁵ ), 132.06 (C ⁷ ), 126.54 (C ⁴ ), 123.68 (C ⁶ ), 123.63 (C ⁸ ), 61.09 (C ¹⁴ ), 35.04 (C ¹¹ ), 14.08 (C ¹⁵ ). Mass spectrum, m / z (Irel,%): 290 (100), 102 (79), 135 (48), 303 (31), 264 (14). Found,%: C 37.83; H 3.22; N, 4.06; S 9.22; Those 36.61. C ₁₁ H ₁₁ NSO ₂ Te. Calculated,%: C 37.87; H 3.18; N, 4.02; S 9.19; Those are 36.57.

S- (1,3-Benztellurazol-2-yl) thiophene-2-carbothioate obtained by reacting 2-mercaptobenztellurazole with thiophene-2-carbonyl chloride in sodium ethylate has the structural formula

Example 3

Sodium ethylate obtained from 0.12 g (4 mmol) of Na and 30 ml of absolute ethanol was placed in a three-necked flask equipped with a stirrer, a refrigerator and a dropping funnel. To the resulting sodium ethylate solution, 1.31 g (5 mmol) of 2-mercaptobenztellurazole was added in small portions over 30 minutes at 30 ° C, then 0.73 g (0.53 ml, 5 mmol) of thiophene-2-carbonyl chloride was added to the reaction mixture, dissolved in 10 ml of absolute ethanol. A precipitate instantly precipitated, the reaction mass was stirred for another 1 h at room temperature. The precipitate was filtered off, washed with ethanol, dried in air and recrystallized from ethanol. Yield 1.45 g (3.88 mmol, 77%), yellow crystals, mp. 218-220 ° C. IR spectrum, ν, cm ^-1 : 3584, 3525 (С-Н), 3045, 735 (CSC in the cycle), 2901 (CH _Ar ), 1613 (С = O), 1577 (N = C), 1455, 1425 (N = C in the loop), 713 (CN), 600, 463 (CS). ¹ H NMR, δ, ppm .: 8.31 dd (1H, ⁷ CH, J 4.9 Hz), 8.25 dd (1H, CH ^13, J 3.9 Hz, 1H), 8.21 dd (1H, CH ^14, J 7.8 Hz), 8.03 d (1H, CH ^4, J 8.0 Hz), 7.52-7.43 d (1H, ⁵ CH, J 4.9 Hz), 7.40 d (1H, ⁶ CH, J 4.0 Hz), 7.29 m (1H, CH ¹⁵ ). ¹³ C NMR spectrum, δ _c , ppm: 180.82 (C ¹¹ ), 158.78 (C ² ), 156.75 (C ⁹ ), 139.13 (C ¹³ ), 137.53 (C ¹² ), 134.05 (C ⁵ ), 132.15 (C ⁷ ), 131.66 (C ¹⁵ ), 129.51 (C ¹⁴ ), 126.74 (C ⁴ ), 125.34 (C ⁶ ), 124.58 (C ⁸ ). Mass spectrum, m / z (Irel,%): 263 (50), 90 (28), 135 (21), 102 (17). Found,%: C 38.70; H 1.95; N, 3.80; S 17.22, Te 34.27. C ₁₂ H ₇ NS ₂ OTe. Calculated,%: C 38.65; H 1.89; N, 3.76; S 17.20; Those 34.22.

S- (1,3-Benztellurazol-2-yl) benzenecarbothioate obtained by reacting 2-mercaptobenztellurazole with benzoyl chloride in sodium ethylate has the structural formula

Example 4

In a three-necked flask equipped with a stirrer, a refrigerator and a dropping funnel, sodium ethylate obtained from 0.2 g (5 mmol) of Na and 30 ml of absolute ethanol was placed. To the resulting sodium ethylate solution, 1.31 g (5 mmol) of 2-mercaptobenztellurazole was added in small portions over 30 minutes at 30 ° C, then 0.70 g (0.58 ml, 5 mmol) of benzoyl chloride dissolved in 10 ml of absolute was added to the reaction mass. ethyl alcohol. The mixture was boiled at a temperature of 50-60 ° C for 2 hours, then stirred at room temperature for 3 hours. The precipitate was filtered off, washed with ethyl alcohol, dried and recrystallized from a solvent mixture of hexane, benzene, ethanol in a ratio of 8: 5: 5. Yield 0.54 g (29%), orange crystals, mp. 238-240 ° C. IR spectrum, ν, cm ^-1 : 3520 (С-Н), 3045 (CH _Ar ), 1643-1596 (С = O), 1577, 1649 (N = C), 1456-1415 (N = C in the cycle) 770, 761 (CN), 694, 683 (CS). ¹ H NMR, δ, ppm .: 8.12 d (1H, ⁷ CH, J 7.6 Hz), 8.04 d (1H, CH ^4, J 7.9 Hz), 7.96 d (1H, ⁵ CH, J 8.2 Hz) , 7.79 dd (1H, CH ⁶ , J 1.1 Hz), 7.55 d (1H, CH ^14.16 , J 7.8 Hz), 7.46 d (H, CH ^13.17 , J 7.9 Hz), 7.24 m (1H, CH ¹⁵ ). ¹³ C NMR spectrum, δ _s , ppm: 189.43 (C ¹¹ ), 154.71 (C ² ), 147.32 (C ⁹ ), 136.49 (C ⁷ ), 134.60 (C ⁵ ), 132.88 (C ^14.16 ) 131.78 (C ⁶ ), 129.17 (C ⁴ ), 124.65 (C ⁸ ), 122.83 (C ¹⁵ ), 120.57 (C ^13.17 ), 120.77 (C ¹³ ). Mass spectrum, m / z (Irel,%): 263 (100), 77 (50), 90 (28), 135 (21), 290 (17). Found,%: C 45.78; H 2.41; N, 3.78; S 8.77; Those 34.82. C ₁₄ H ₉ NSOTe. Calculated,%: C 45.83; H 2.47; N, 3.82; S 8.74, Te 34.78.

S- (1,3-Benztellurazol-2-yl) -4-nitrobenzenecarbothioate obtained by reacting 2-mercaptobenztellurazole with p-nitrobenzoyl chloride in sodium ethylate has the structural formula

Example 5

In a three-necked flask equipped with a stirrer, a refrigerator and a dropping funnel, sodium ethylate obtained from 0.2 g (5 mmol) of Na and 30 ml of absolute ethanol was placed. To the resulting sodium ethylate solution, 1.31 g (5 mmol) of 2-mercaptobenztellurazole was added in small portions over 30 minutes at 30 ° C, then 0.92 g (5 mmol) of p-nitrobenzoyl chloride dissolved in 10 ml of absolute ethyl alcohol was added to the reaction mass. alcohol. The mixture was boiled at a temperature of 50-60 ° C for 1.5 h. After cooling to room temperature, 100 ml of ice water was poured into the reaction mass. The precipitate was filtered off, washed with ethyl alcohol, dried in air and recrystallized from acetonitrile. Yield 1.14 g (56%), dark red crystals, mp. 219-221 ° C. IR spectrum, ν, cm ^-1 : 3626-3423 (С-Н), 3045, 2955, 2890 (CH _Ar ), 1653-1617 (С = O), 1567 (N = C), 1444, 1431 (N = C in the cycle), 1328, 1308, 1278 (NO ₂ ), 792 (CN), 756 (CS). ¹ H NMR, δ, ppm .: δ 8.23-8.15 m (2H, CH ^13,17), d 8.10 (1H, ⁷ CH, J 1.2 Hz), 7.85 d (1H, CH ^4, J 1.3 Hz ), 7.70 d (1Н, СН ⁶ , J 1.3, 0.6 Hz), 7.70 d (1Н, СН ⁵ , J 0.6 Hz), 7.66-7.59 m (2Н, СН ^14.16 ), 7.27 dd (1Н, СН ⁶ , J 1.3, 0.6 Hz). ¹³ C NMR spectrum, δ _s , ppm: 171.61 (C ¹¹ ), 168.07 (C ² ), 161.45 (C ⁹ ), 140.61 (C ⁷ ), 133.70 (C ⁵ ), 133.38 (C ^14.16 ) 132.10 (C ⁶ ), 126.81 (C ⁴ ), 124.13 (C ⁸ ), 123.60 (C ¹⁵ ), 121.07 (C ^13.17 ), 120.26 (C ¹² ). Mass spectrum, m / z (Irel,%): 290 (100), 263 (91), 134 (86), 76 (63), 102 (50). Found,%: C 40.79; H 1.93; N 6.77; S 7.82, Te 31.05. C ₁₄ H ₈ N ₂ SO ₃ Te. Calculated,%: C 40.82; H 1.96; N, 6.80; S 7.78, Te 30.98.

S- (1,3-Benztellurazol-2-yl) (2-thioxo-1,3-benztellurazol-3-yl) ethanethioate obtained by reacting 2-mercaptobenztellurazole with oxalyl chloride in sodium ethylate has the structural formula

Example 6

Sodium ethylate obtained from 0.16 g (7 mmol) of Na and 30 ml of absolute ethanol was placed in a three-necked flask equipped with a stirrer, a refrigerator, and a dropping funnel. To the resulting sodium ethylate solution, 6 g (2.3 mmol) of 2-mercaptobenztellurazole were added in small portions over 30 minutes at 30 ° C, then 0.22 g (0.15 ml, 3.5 mmol) of oxalyl chloride dissolved in 5 ml was added to the reaction mass. absolute ethyl alcohol. The mixture was stirred at 55-60 ° C for 2 hours and at room temperature for 1 hour. The precipitate was filtered off, washed with hot ethanol, dried in air and recrystallized from acetonitrile. Yield 1.45 g (66%), yellow crystals, mp. 254-256 ° C. IR spectrum, ν, cm ^-1 : 3627-3425 (С-Н), 2950 (CH _Ar ), 1653 (NC (O), 1617 (С = O), 1561 (N = C), 1445, 1430 (N = C in the cycle), 1388 (C = S), 755, 670 (CS). NMR spectrum ¹ Н δ, ppm: 8.00 dd (1H, СН ⁷ , J 7.8, 1.7 Hz), 7.83 d (1Н , CH ¹⁴ , J 8.4 Hz), 7.38 d (1H, CH ⁴ , J 13 Hz), 7.11 m (1H, CH ¹⁷ ), 6.73 d (1H, CH ⁵ , J 9.1 Hz), 6.60 m (1H, CH ¹⁶ ), 6.38 m (1Н, СН ⁶ ), 6.23 d (1H, СН ¹⁵ , J 9.1 Hz). ¹³ С NMR spectrum, δ _s , ppm: 171.61 (С ¹¹ ), 168.45 (С ¹² ), 161.45 (С ⁹ ), 160.81 (С ² ), 140.62 (С ¹⁹ ), 140.62 (С ²¹ ), 133.70 (С ¹⁷ ), 132.38 (С ⁵ ), 132.10 (С ⁷ ), 132.10 (С ¹⁵ ), 126.81 ( C ¹⁶ ), 124.13 (C ¹⁴ ), 123.60 (C ⁴ ), 121.07 (C ⁶ ), 120.26 (C ¹⁸ ), 97.05 (C ⁸ ). ¹³ C NMR spectrum, δ _s , ppm: 171.61 (C ¹¹ ), 168.45 (C ¹² ), 161.45 (C ⁹ ), 160.81 (C ² ), 140.62 (C ¹⁹ ), 140.62 (C ²¹ ), 133.70 (C ¹⁷ ), 132.38 (C ⁵ ), 132.10 (C ⁷ ) , 132.10 (С ¹⁵ ), 126.81 (С ¹⁶ ), 124.13 (C ¹⁴ ), 123.60 (C ⁴ ), 121.07 (C ⁶ ), 120.26 (C ¹⁸ ), 97.05 (C ⁸ ). Found,%: C 33.23; H 1.37; N 4.79; S 11.14, Te 44.13. C ₁₆ H ₈ N ₂ S ₂ O ₂ Te ₂ . Calculated,%: C 33.16; H 1.39; N, 4.83; S 11.06, Those 44.03.

We conducted tests of biological activity in the laboratory of biochemistry and biophysics (act attached).

The content of sulfhydryl groups in proteins and tissues is an important indicator of the conformational modification of proteins under the influence of various factors.

The content of sulfhydryl groups was determined in the blood plasma of outbred laboratory rats contained in the vivarium of FSBEI HPE “Dagestan State University” on a standard diet. In the experiment were used animals of both sexes, 2-3 months old, weighing from 180 to 200 g.

The following series of tests were carried out.

1. The study of the total content of SH-groups in the blood plasma of intact animals (control).

2. The study of the total content of SH-groups in the blood plasma of animals with the introduction of a solution of 0.01 g / ml of the studied substances in dimethyl sulfoxide (DMSO) at a dose of 25 mg per kg live weight (experiment).

3. The study of the content of total protein, glucose, cholesterol, bilirubin in the blood plasma of intact animals (control).

4. The study of the content of total protein, glucose, cholesterol, bilirubin in the blood plasma of animals with the introduction of a solution of 0.01 g / ml of the studied substances in dimethyl sulfoxide (DMSO) at a dose of 25 mg per kg live weight (experience).

All tests were carried out in triplicate; in experiments with laboratory animals, all the rules for humane treatment of animals were observed. In total, 3 animals were used in each series.

The results were subjected to variation-statistical processing using t-student test. Differences were considered significant at p <0.05.

The results of the study of the content of sulfhydryl groups in the blood plasma of laboratory rats with the introduction of the synthesized derivatives of 2-mercaptobenztellurazole are shown in table 1.

* - significant difference relative to control

As follows from table 1, the intraperitoneal administration of synthesized 2-mercaptobenztellurazole derivatives to the test subjects caused a significant decrease in the total content of SH-groups in rat blood plasma, with the exception of substance 6 (S- (1,3-benztellurazol-2-yl) (2-thioxo 1,3-benztellurazol-3-yl) ethanethioate).

The most powerful effect was exhibited by 2 S- (1,3-Benztellurazol-2-yl) thiophene-2-carbotioate (substance 3): the decrease in the total sulfhydryl groups was 32% relative to the control.

Thus, the synthesized and tested derivatives of 2-mercaptobenztellurazole in vivo possibly change the conformation of proteins by reducing the content of sulfhydryl groups.

Thus, the most pronounced effect of the administration of synthesized 2-mercaptobenztellurazole derivatives to the test subjects is a decrease in the content of thiol groups in blood plasma and a decrease in glucose content.

Claims (2)

New derivatives of 2-mercaptobenztellurazole with biological activity, having the structural formula