Derivatives of aminothiols

FIELD: organic chemistry, medicine, physiology.

SUBSTANCE: invention relates to agents for regulation (maintaining or suppression) of physical working ability and/or adaptation to different variants represented by solvated complex compounds of the general formula (I): Kat^m+[L¹ _qEL²]An^n- x p.Solv (I) wherein L¹ means aminothiols of the formula: R¹NHCH(R²)(CH₂)_1-2SR³ wherein R¹ means hydrogen atom (H), (C₁-C₂₀)-alkyl or RCO; R means (C₁-C₁₉)-alkyl; R² means H or carboxyl; R³ means H, (C₁-C₂₀)-alkyl, (C₂-C₂₀)-alkenyl or benzyl; q = 1, 2 or 3; L² means halogen atom, water and/or organic ligand. For example, bis-(N-acetyl-L-cysteinato)aquozinc (II) diheptahydrate suppresses physical working ability and in the dose 50 mg/kg increases reviving time of mice by 6 times and cats - by 2.8fold under conditions of acute hypoxia with hypercapnia, and increases reviving time of mice by 4 times under conditions of acute hypobaric hypoxia. Under the same conditions the known antihypoxic agents amtizol, acizol or mexidol are inactive or less active significantly by their activity. Bis-(N-acetyl-L-cysteinato)-ferrous (II) pentahydrate is more active as compared with the known antihypoxic agents and protects experimental animals in 4 variants of hypoxia. Bis-(N-acetyl-L-cysteinato)zinc (II) sulfate octahydrate is similar to enumerated compounds by its antihypoxic activity.

EFFECT: valuable medicinal properties of compounds.

4 cl, 1 dwg, 11 tbl, 33 ex

The invention relates to new compounds of the number of complex compounds of bimetallic with, in particular, biological activity and which may find use as pharmaceuticals.

It is well known that the high biological activity of trace elements is determined by their biochemical function in the structure of enzymes and enzyme systems as working tools last. Some contribution to their biological activity have also been low-molecular-weight metabolites. Efficiency coming from outside in the animal organism of trace elements is largely determined by the presence in the digestive tract of suitable ligands necessary for their biological transport. Low molecular weight metabolites of trace elements, which is equal to the right can be considered as metabolites of organic ligands, can simultaneously perform the function of protecting the body from exposure to a variety of alien factors physical, chemical or biological nature. These facts collectively formed the basis of the scientific basis for the development of complex compounds of Bioelements multi-purpose [1-3].

One of the most suitable ligands for the complex compounds of Bioelements for medical purposes can be considered natural aminothio the s. These compounds find property good chelators and play a very important role to control the thiol-disulfide equilibrium in biological systems. Therefore, complex compounds of Bioelements with aminosilane can be considered as prodrugs in relation not only to bioelement, but also to the ligand, and the most durable of them as self-medication purposes. This idea has not yet been expressed in the form of a systematic experimental study, however, you can specify on a separate development of this plan. Thus, in the patent [4] described a group of precursors of glutathione, including the form of complex compounds with some Bioelements, based on ideas about the important role of glutathione in the regulation of biochemical thiol-disulfide balance.

However, the cited work does not exhaust the possible choices as ligands, and the bio-elements and methods for their inclusion in the design of complex compounds. In addition, in this paper when discussing the possible beneficial role of compounds aminothiols lists only some pathological situation and says nothing about their useful manifestations in extreme situations and in normal physiology.

The task of this invention are new chemical compounds having, in particular, biological engineering is th activity.

This problem is solved derived aminothiols General formula I

Kat^m+[L¹qL²]Anⁿ.p.Solv,

where L¹- aminothiol R¹NHCH(R²)(CH₂)_1-2SR³and where R¹is hydrogen, alkyl (C_1-20or the group RCO, R is alkyl (C_1-19; R²is hydrogen or carboxyl, R³is hydrogen, alkyl With_1-20alkenyl_2-20or benzyl, and q can take values 1, 2 or 3;

L²- halogen, water and/or organic ligand from among substituted by one or two alkilani_1-20one or two hydroxy or oxymethylene groups, pyridine, hydroxy coumarin derivatives, nicotinic, p-aminobenzoic, phenylacetic acid, or ascorbic acid, or arginine;,

E-Cu(I), CA(II), Co (II), Cu (II), Fe(II), Mn(II), Ni (II), Zn(II)

Co (III), Cr (III), Ge(IV), Ti (IV), V(IV);

Kat is absent or represented by a cation 2-ethyl-6-methyl-3-hydroxypyridine or inorganic cation of an alkaline or alkaline-earth metal;

An absent or represented by the anion of p-toluenesulfonic acid or sulfate;

Solv - water, and R can take values from 0 to 8.5;

m can take values from 0 (with the exception of compound I, where R¹- CH₃CO, R²- COO, L²- no, n - 0, p - 0) to 2;

n can take values from 0 to 3.

Preferred are compounds I, where

L¹- N-acetyl-L-sistei is; L²- water, e - Zn(II), q - 2; R - 2,5; m=n=0,

or the compounds I, where L¹- N-acetyl-L-cysteine; L²no, e - Fe(II); q - 2; p - 5; m=n=0,

or the compounds I, where L¹- N-acetyl-L-cysteine; L otsutstvuet, e - Zn (II), q - 2; An - sulfate; p - 8; m is 0; n is 2.

The synthesis of compounds of General formula (I) can be any of the known literature methods. In this patent the development of these selected only those that are either not accompanied by the formation of by-products, or may result in the formation of volatile products that are easy to catch. The General method consists of mixing calculated amounts of reactants in water or in aqueous alcohol at a temperature of 20-80°until the reaction is completed. Then the solvent and volatile products of the reaction is distilled off in vacuum and bring the residue to constant weight.

The following examples illustrate the synthesis of compounds according to the invention and their biological activity.

Example 1. N-Acetyl-L-cysteinato(akvo)zinc (II) disabilitati.

Mixed 3.00 g of N-acetyl-L-cysteine and a 4.03 g of the acetate of zinc (II) dihydrate in 15 ml of water at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 1.5 hours. Then distilled water acetic acid under vacuum (10-15 Torr) and bring the residue to constant weight. Exit 5, 27, Trasl. 252°C. Found, %: C 20,47; H5,09; N 4,62. C₅H₉NO₄SZn. 2,5 H₂O. Calculated, %: C 20,74; N To 4.87; N 4,84.

Example 2. N-Acetyl-L-cysteinato(akvo)cobalt(II)]tetracampidae.

Mixed 3.00 g of N-acetyl-L-cysteine and 4,58 g of cobalt acetate(II) tetrahydrate in 15 ml of water at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 1.5 hours. Then distilled water acetic acid under vacuum (10-15 Torr) and bring the residue to constant weight. The yield of 6.52, So different. 64-66°C. Found, %: C 18,56; N. Of 5.81; N 4,18. C₅H₉NO₄S₂Co.4,5 H₂O. Calculated, %: C 18,81; N. Of 5.68; N 4,39.

Example 3. N-Acetyl-L-systemnational(III).

Mix of 5.00 g of N-acetyl-L-cysteine and 8,19 g to Balt(III)examineralfred in 70 ml of water at 60°and incubated for 3.5 hours at 18-20°C. Then evaporated to about 50 ml of aqueous ammonia under vacuum (10-15 Torr), separating the precipitated product by filtration, washed his 15-20 ml of water and brought to a constant weight. The yield of 6.71, So different. 227°C. Found, %: C 27,12; N 2,79; N 6,52. With₅H₆NO₃SCo. Calculated, %: 27,41; N Was 2.76; N 6,39.

Example 4. N-Acetyl-L-cysteinato (akvo) copper (I) semihydrate.

Mix is 4.21 g of N-acetyl-L-cysteine and 1.84 g of copper oxide (I) in 8 ml of water and stirred for 1.5-2 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. The yield of 6.52, Trasl. 136°C. Found, %: C 23,47; N 4,51; N 5,38. C₅H₁₀NO_{4 SCu. 0,5H2O. Calculated, %: C 23,76; N. Of 4.66; N Of 5.05.}

Example 5. Bis(N-acetyl-L-cysteinato)equating(II) disabilitati.

Mix of 5.00 g of N-acetyl-L-cysteine and to 3.36 g of the acetate of zinc(II) dihydrate in 20 ml of water at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 0.5 hours. Then distilled water acetic acid under vacuum (10-15 Torr) and bring the residue to constant weight. Exit 7, 33, So different. 112-118°C. Found, %: C 26,22; N 5,44; N 6,37. C₁₀H₁₆N₂O₆S₂Zn. 2,5 H₂O. Calculated, %: C 26,53; N 5,12; N Is 6.19.

Example 6. Bis(N-acetyl-L-cysteinato) cobalt (II) tricameral.

Mix of 5.00 g of N-acetyl-L-cysteine and 3,82 g of cobalt acetate (II) tetrahydrate in 20 ml of water at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 1.5 hours. Then distilled water acetic acid under vacuum (10-15 Torr). Output for 6.81, Trasl. 56°C. Found, %: C 26,42; N 5,42, N 5,93. With₁₀H₁₆H₂O₆S₂With. 3,5H₂O. Calculated, %: C 26,91; N 5,19; N 6,28.

Example 7. Bis (N-acetyl-L-cysteinato) cobalt (III) trihydrate.

Mix of 6.00 g of N-acetyl-L-cysteine and to 4.92 g of cobalt(III)examineralfred in 30 ml of water at 50°and incubated for 3.5 hours at 18-20°C. and Then distilled water ammonia under vacuum (10-15 Torr), separating the precipitated product by filtration and washed it 10-15 ml of water and bring the OS is atok until constant weight. Output 10,89, Trasl. 111°C. Found, %: C 27,22; N 5,23; N OF 6.31 .C₁₀H₁₅N₂O₆S₂Co.3 H₂O. Calculated, %: C 27,53; N Is 4.85; N, 6.42 Per.

Example 8. Bis(N-acetyl-L-cysteinato)manganese(II) pentahydrate.

Mix of 5.00 g of N-acetyl-L-cysteine and 3.75 g of manganese acetate(II) tetrahydrate in 20 ml of water at 18-20°With, bring bring the temperature of the reaction medium up to 60°C and stirred at this temperature for 1.5 hours. Then distilled water acetic acid under vacuum (10-15 Torr) and bring the residue to constant weight. The output of 7.25, Trasl. 76°C. Found, %: C 25,42; N 5,70; N 6,11. C₁₀H₁₆N₂O₆S₂Mn. 5H₂0. Calculated, %: C 25,59; N To 5.58; N 5,97.

Example 9. Bis (N-acetyl-L-cysteinato) iron (II) pentahydrate.

Mix of 5.00 g of N-acetyl-L-cysteine and 3.77 g of the acetate of iron (II) tetrahydrate in 20 ml of water at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 1.5 hours. Then distilled water acetic acid under vacuum (10-15 Torr) and bring the residue to constant weight. Output 7,16, So different. 113°C. Found, %: C 25,07; N 5,42; N 5,61. C₁₀H₁₆N₂O₆S₂Fe. 5H₂O. Calculated, %: C 25,54; N 5,69; N 5,96.

Example 10. Bis (2-methyl-5-ethyl-3-hydroxypyridine) bis (N-acetyl-L-cysteinato)-acculturation (IV) tetracampidae.

Mix of 5.00 g of N-acetyl-L-cysteine, 2,73 g esculetin and 4,20 g 2-methyl-5-ethyl-3-is hydroxypyridine with 15,32 millimole hydrated Titanic acid in 30 ml of water at 18-20° With increase of the temperature of the reaction medium up to 60°C and stirred at this temperature for 2.5 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 13,81, So different. 124°C. Found, %: C 46,25; N 6,01; N 6,18. C₃₅H₄₂N₄O₁₂S₂Ti. 4,5H₂O. Calculated, %: C 46,51; N 5,69; N 6,20.

Example 11. Bis(N-acetyl-L-cysteinato) acculturation (IV).

Mix 5.0 g of N-acetyl-L-cysteine, 2,73 g esculetin and 15,32 millimole hydrated Titanic acid in 30 ml of water at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 2.5 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 8,46 was So different. 112°C. Found, %: C 41,32; N 4,01; N 4,86. C₁₉H₂₀N₂O₁₀S₂Ti. Calculated, %: C 41,61; N 3,68; N 5,11.

Example 12. Magnesium bis(N-acetyl-L-cysteinato) acculturation(IV) trihydrate

Mix 3.25 g of N-acetyl-L-cysteine, 1,77 g esculetin and 0.40 g of magnesium oxide from 9.46 to millimole hydrated Titanic acid in a mixture of 15 ml of water and 5 ml of alcohol at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 2 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 6,21 was So different. 94°C. Found, %: C 36,22; N. Of 3.25; N 4,62. C₁₉H₁₈N₂O₁₀S₂2O. Calculated, %: C 36,53; H 2,90; N 4,48.

Example 13. Magnesium bis (N-acetyl-L-cysteinato)bis (esculenta)titanium(IV) pentahydrate.

Mix of 5.00 g of N-acetyl-L-cysteine, 5,46 g esculetin and 0.62 g of magnesium oxide with 15,32 millimole hydrated Titanic acid in a mixture of 25 ml of water and 5 ml of alcohol at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 2.5 hours. Then distilled water alcohol under vacuum (10-15 Torr) and bring the residue to constant weight. Output 12,88 was So different. 108°C. Found, %: C 39,69; N 3,12; N 3,11. C₂₈H₂₄N₂O₁₄S₂MgTi. 5H₂O. Calculated, %: 40,09; N 2,88; 3,34 N.

Example 14. Bis(N-acetyl-L-cysteinato)germanium(IV) trihydrate.

Mix 5.0 g of N-acetyl-L-cysteine with 15,32 millimole hydrated germanium acid in 15 ml of water at 18-20°To increase the temperature of the reaction medium up to 60°C and stirred at this temperature for 2.5 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 6,87, Trasl. 152°C. Found, %: C 26,82; N To 4.62; N 6,02. C₁₀H₁₄N₂O₆S₂Ge. 3H₂O. Calculated, %: C 26,75; N. Of 4.49; N 6,24.

Example 15. Bis(S-allyl-L-homocysteine)calcium(II) trihydrate.

Mix 4,48 g S-allyl-L-homocysteine from 0.72 g of calcium oxide in 15 ml of water at 18-20°To increase the temperature of the reaction medium up to 60°and With mix PR is this temperature for 1 hour. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. The yield of 5.68, So different. Number 109-121°C. Found, %: C 37,64; N 7,02; N of 5.83. C₁₄N₂₄N₂O₄S₂Ca. 3H₂O. Calculated, %: C 37,99; N 6,83; N 6,33.

Example 16. Bis(S-benzyl-L-homocysteine)manganese(II) tetrahydrate.

Mix of 4.46 g of S-benzyl-L-homocysteine 2.43 g of manganese acetate (II) tetrahydrate in 15 ml of water at 18-20°With, bring the temperature of the reaction medium up to 60°C and stirred at this temperature for 2 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 5,70, So different. 96-117°Found, %: C 45,69, N 6,55; N of 4.83. C₂₂H₂₈N₂O₄S₂Mn. 4H₂O. Calculated, %: C 45,91; N 6,30; N 4,87.

Example 17. Sodium [N-acetyl-L-cysteinato(nicotinate)zinc (II) sulfate tetrahydrate.

Mix 1.73 g of N-acetyl-L-cysteine and 1.31 g of nicotinate and 3.06 g of zinc sulfate (II) heptahydrate in 15 ml of water at 18-20°With, then gradually added with stirring 0.56 g sodium, increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 1.5 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. The yield of 6.52, So different. 179°C. Found, %: C 23,96; N. Of 4.35; N 4,86. C₁₁H₁₃N₂O₉S₂NaZn. 4H₂0. Calculated, %: 24,38; N 3,91; N 5,17.

Example 18. Bis(L-cysteinato)zinc(II) sulfate(that is ilat) octanamide.

Mix of 1.61 g of L-cysteine, 2,53 g of the monohydrate of p-toluenesulfonic acid, 1, 46 g of dihydrate zinc acetate(II) and of 2.27 ml, 24.4% of sulfuric acid in 15 ml of water at 18-20°With, then increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 1.5 hours. Distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 6,00 was So different. 74°C. Found, %: 26,34; N 5,43, N 6,17. C₂₀H₂₈N₂O₁₄S₃Zn.8,5H₂O. Calculated, %: 26,71; N 5,04; N 5,96.

Example 19. Cysteamine(pyridoxine)chlorotic(II) the uranyl.

Mix 1.20 g group probably facilitates hydrochloride, 1,79 g of pyridoxine hydrochloride and 2, 32 g of dihydrate zinc acetate(II) in 15 ml of water at 18-20°With, then increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 2 hours. Distilled water mixed with volatile acids in vacuum (10-15 Torr) and bring the residue to constant weight. The output of 4.77, So different. 166°C. Found, %: C 25,98; N 6,63; N by 5.87. C₁₅H₂₇N₅O₅S₂Ni.7,5H₂O. Calculated, %: 26,44; N To 6.43; N 6,17.

Example 20. Sodium D,L-methionate(p-aminobenzoate)copper(II) heptahydrate.

Mix 1.22 g of D,L-methionine, 1.12 g of p-aminobenzoic acid and 2.03 g of copper acetate(II) tetrahydrate in 15 ml of water at 18-20°With, then gradually added with stirring to 0.44 g of sodium, increase the temperature of the reaction mixture to 60°and mix With p and this temperature for 1.5 hours. Then distilled water acetic acid under vacuum (10-15 Torr) and bring the residue to constant weight. The yield of 6.52, Trasl. above 210°C. Found, %: C Of 28.72; N 3,12; N 5,86. C₁₂H₁₆N₂O₄SCuNa. 7H₂O. Calculated, %: C 29,00; N 3,24; N 5,64.

Example 21. Bis [(D,L-methionate(L-cysteinato)chromium(III)] trisulfate octahedral.

Mix of 1.32 g of D,L-methionine, 1.07 g of L-cysteine and 3,17 g of sulfate of chromium(III) octadecahydrate in 15 ml of water at a temperature of 18-20°To increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 1 hour. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. The output value of 4.76, So different. 221°C. Found, %: C 17,36; N 3,18; N is 5.06. C₁₆H₃₆N₄O₂₀S₇Cr₂. 8H₂O. Calculated, %: C 17,84; N 3,37; N 5,20.

Example 22. Cysteamine(L-arginine)Nickel (II) toilet heptageniidae.

Mix 1.18 g group probably facilitates hydrochloride, of 1.80 g of L-arginine, 1.97 g of the monohydrate of p-toluenesulfonic acid and 2.58 g of leads to compounds, which Nickel(II) tetrahydrate in 15 ml of water at 18-20°With, then increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 2 hours. Distilled water hydrogen chloride in vacuum (10-15 Torr) and bring the residue to constant weight. Output 6,38 was So different. 64°C. Found, %: C 29,12; N. Of 6.75; N 11,18. C₁₅H₂₇N₅O₅S₂Ni. 7,5H₂O. Calculated, %: 29,37; N 6,41; 11,42.

Example 23. L-Cysteinato (phenylacetate)vanadyl acidic uranyl sulfate.

Mix 1.44 g of L-cysteine, of 1.62 g of phenylacetate and 2, 58 g of the three-hydrate sulphate vanadyl in 15 ml of water at 18-20°With, then increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 1.5 hours. Distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. The output of 6.25 was So different. 71°C. Found, %: C 24,59; N the ceiling of 5.60; N 2,31. C₁₁H₁₆NO₉S₂V.6H₂O. Calculated, %: C 24,96; N 5,33; N 2,64.

Example 24. Bis(N-acetyl-L-cysteinato)zinc(II) sulfate octahydrate.

Mix at 3.35 g of N-acetyl-L-cysteine from 2.95 g of zinc sulfate(II) heptahydrate in 15 ml of water at 18-20°With, then increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 2 hours. Distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 6,46 was So different. 163°C. Found, %: From 18.76; H 3,02; N 4,56. C₁₀H₁₈N₂O₁₀S₃Zn.8H₂O. Calculated, %: From 19.00; N 2,87; N 4,43.

Example 25. Disodium bis(N-acetyl-L-cysteinato)zinc(II) tetrahydrate.

Mix of 3.73 g of N-acetyl-L-cysteine and 2.51 g of the acetate of zinc(II) dihydrate in 15 ml of water at 18-20°With, then gradually added with stirring to 1.21 g soda, raise the temperature of the reaction mixture to 60°C and stirred at this temperature for 2 hours. Distilled water under vacuum (10-15 Torr) and bring the STATCOM to constant weight. Output 5,79 was So different. 166°C. Found, %: C 23,56; N To 2.57; N 5,31. C₁₀H₁₄N₂O₆S₂Na₂Zn.4₂O. Calculated, %: C 23,75; N To 2.79; N, 5,54.

Example 26. Sodium bis(N-acetyl-L-cysteinato)zinc(II) dihydrate.

Mix 3,93 g N-acetyl-L-cysteine and 2.64 g of the acetate of zinc(II) dihydrate in 15 ml of water at 18-20°With, then gradually added with stirring 0.64 g of soda, raise the temperature of the reaction mixture to 60°C and stirred at this temperature for 2 hours. Distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 5,42 was So different. 163°C. Found, %: C 27,12; N 3,16; N 5,94. C₁₀H₁₅N₂O₆S₂NaZn.2H₂O. Calculated, %:C 26,82; N 3,38; N 6,26.

Example 27. N-Acetyl-L-cysteinato(nicotinate)zinc(II) disabilitati.

Mix 2,32 g N-acetyl-L-cysteine, 1,75 g nicotinate and 3.12 g of the acetate of zinc(II) dihydrate in 25 ml of water and stirred at a temperature of 60°1.5-2 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output, 5,65 So different. 195°C. Found, %: C 32,96; N Is 3.21; N 7,21. C₁₁H₁₃N₂O₅S₂Zn.2,5H₂O. Calculated, %: C Represented 33.47 Per; N. Of 3.06; N 7,10.

Example 28. Sodium N-Acetyl-L-cysteinato(nicotinate)zinc(II) tetrahydrate.

Mix 2.17 g of N-acetyl-L-cysteine, 1.64 g of nicotinate and of 2.92 g of the acetate of zinc(II) dihydrate in 20 ml of water at 18-20°With, then gradually under stirring to relax the Ute 0.71 g sodium, raise the temperature of the reaction mixture to 60°C and stirred at this temperature for 1.5 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 5,88 was So different. 82°C. Found, %: C 29,49; N Is 2.74; N 6,18. C₁₁H₁₁N₂O₅SNaZn.4H₂O. Calculated, %: C 29,78; H 2,50; N Of 6.31.

Example 29. Sodium N-acetyl-L-cysteinato (nicotinate)the chlor-zinc(II) tetracampidae.

Mix 1.88 g of N-acetyl-L-cysteine, 1.42 g of nicotinate, of 0.68 g of sodium chloride and of 2.53 g of the acetate of zinc(II) dihydrate in 15 ml of water at 18-20°With, then gradually added with stirring and 0.61 g of sodium, increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 1.5 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. The yield of 5.68, So different. 163°C. Found, %: C 26,87; N 2,85; Cl 7,16; N 5,47. C₁₁H₁₂N₂O₅SNaZn. 4,5H₂O. Calculated, %: 27,01; N 2,47; Cl 7,25; N5,73.

Example 30. Disodium nicotinate(N-acetyl-L-cysteinato)zinc(II) pentahydrate.

Mix of 2.05 g of N-acetyl-L-cysteine, 1.55 g of nicotinate and 2.76 g of the acetate of zinc(II) dihydrate in 15 ml of water at 18-20°With, then gradually added with stirring to 1.33 g of sodium, increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 2 hours. Distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output between 6.08, Try the L. 230°C. Found, %: C 26,95; N 2,41; N 5,64. C₁₁H₁₁N₂O₅SNa₂Zn. 5H₂O. Calculated, %: C 27,26; N To 2.29; N 5,78.

Example 31. N-Acetyl-L-cysteinato(nicotinate)zinc(II) sulfate octahydrate.

Mix 1,82 g N-acetyl-L-cysteine, 1,38 g nicotinate and 3.21 g of zinc sulfate(II) katakata in 15 ml of water and stirred at a temperature of 60°1.5-2 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 6,57, So different. 132°C. Found, %: C 22,51; N 1,96; N to 4.52. C₁₁H₁₄N₂O₉S₂Zn.8H₂O. Calculated, %: 22,32; N. Of 2.38; N 4,73.

Example 32. N-Acetyl-L-cysteinato(nicotinate)zinc(II) sulfate toilet octahedral.

Mix of 1.32 g of N-acetyl-L-cysteine, 0,99 g nicotinate, 1,53 g of the hydrate p-toluenesulfonic acid and 2,31 g of zinc sulfate(II) katakata in 15 ml of water and stirred at a temperature of 60°1.5-2 hours. Then distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. The yield of 6.02, So different. 179°C. Found, %: C 28,64; N 3,05; N 3,74. C₁₈H₂₂N₂O₁₂S₃Zn.7H₂O. Calculated, %: C 28,98; N 2,97; N 4,75.

Example 33. N-Acetyl-L-cysteine(L-ascorbate)vanadium(IV) sesquihydrate.

Mix of 1.39 g of N-acetyl-L-cysteine, 2,02 g of L-ascorbate and 0.95 g of vanadium oxide(IV) dihydrate in 15 ml of water at 18-20°With, then increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 1.5 hours Distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 4.26 deaths, So different. above 146°C. Found, %: C 29,41; N 3,12; N 3,94. C₉H₁₁NO₈SV.1,5H₂O. Calculated, %: C 29,12; N 2,99; N Of 3.77.

Example 34. N-Acetyl-L-cysteine(L-ascorbate)chromium(III) tetracampidae.

Mix of 1.39 g of N-acetyl-L-cysteine, 2,02 g of L-ascorbate and of 1.65 g of chromium acetate(III) (chromium content 36,15%) in 15 ml of water at 18-20°With, then increase the temperature of the reaction mixture to 60°C and stirred at this temperature for 1.5 hours. Distilled water under vacuum (10-15 Torr) and bring the residue to constant weight. Output 4,88, Trasl. above 142°C. Found, %: C 24,99; N. Of 2.83; N 3,11. C₉H₁₂NO₈SCr.4,5H₂O. Calculated, %: 25,30; N. Of 2.83; N 3,28.

These compounds were subjected to biological tests on experimental models of stress reactions that occur in extreme situations. As such, were selected increased physical activity, which should be overcome by the person or in intense sports activities, either in an emergency or other dangerous situations. This option stress response was simulated on the model of running animals (mice) along the endless track (treadmill) or model in a swimming pool. The second variant of the stress response - the extreme situation caused by the lack of molecular oxygen at departure animal organism vital functions. Often, for various reasons (period rehabilit the tion after severe illness, the specifics of the performance of professional duties and the like) have to operate in conditions of physical inactivity. This type of stress response was also symitirovan on animal model. In addition, some compounds were tested on the model of the stress response, is complicated by additional factors (vibration, hypercapnia, and so on). The results of the tests are summarized in tables No. 1-11 and one drawing. As can be seen from the tables, the tested compounds have characteristic physiologically compatible compounds modulating (with the change of the sign of the effect) the nature of the manifestation of biological activity, as dependent on the structure of the compound and dose.

Sources of information

1. E.A.Parfenov, G.E.Zaikov. Biometals and Ligands for Anticancer Drug Design: Molecular Mechanisms of Superoxide Dismutase Models Antitumor Effects // Nova Science Publishers. - New York. - 1998. - P.380.

2. E.A.Parfenov, G.E.Zaikov. Biometals and Ligands for Anticancer Drug Design: Superoxide Dismutase Models for Combined Tumor Therapy // Nova Science Publishers. - New York. - 2001. - P.278.

3. E.A.Parfenov, G.E.Zaikov. Biotic Type Antioxidants: The Perspective of the Search Area of Novel Chemical Drugs // VSP. - Utrecht-Boston-Tokyo. - 2000. - P. 559.

4. Patent USA No. 13947, class a 61 K 31/198, 2003.

1. Derivatives aminothiols General formula I

Kat^m+[L¹ _qL²]Anⁿ·p.Solv,

where L¹- aminothiol R¹NHCH(R²)(CH₂)_1-2SR³where R¹is hydrogen, alkyl With_1-20or the group RCO, R is alkyl (C_1-19; R²is hydrogen or carboxyl, R³is hydrogen, alkyl With_1-20alkenyl_2-20or benzyl, and q can take values 1, 2 or 3;

L²- halogen, water and/or organic ligand from among substituted by one or two alkilani_1-20; one or two hydroxy or oxymethylene groups, pyridine, hydroxy coumarin derivatives, nicotinic, p-aminobenzoic, phenylacetic acid, or ascorbic acid, or arginine, or missing;

E - Cu (I), CA (II), Co (II), Cu (II), Fe (II), Mn (II), Ni (II), Zn (II), Co (III), Cr (III), Ge (IV), Ti (IV), V (IV);

Kat is missing and who and presents a cation 2-ethyl-6-methyl-3-hydroxypyridine or inorganic cation of an alkaline or alkaline earth metal;

An - is absent or represented by the anion of p-toluenesulfonic acid or sulfate;

Solv - water;

R can take values from 0 to 8.5;

m can take values from 0 (with the exception of compound I, where R¹- CH₃CO., R²- COO, L²- no, n=0, p=0) to 2;

n can take values from 0 to 3.

2. Derived aminothiol General formula I according to claim 1, where L¹- N-acetyl-L-cysteine; L²-water, e-Zn (II), q=2; p=2,5; m=n=0.

3. Derived aminothiol General formula I according to claim 1, where L¹- N-acetyl-L-cysteine; L²- no, uh - Fe (II); q=2; p=5; m=n=0.

4. Derived aminothiol General formula I according to claim 1, where L¹- N-acetyl-L-cysteine; L²- no, uh - Zn (II), q=2; An - sulfate; p=8; m=0; n=2.