Derivative azole, the method of production thereof, and pharmaceutical composition

 

(57) Abstract:

The invention can be used in the chemistry of heterocyclic compounds and medicine. Describes the new derivative azole General formula I

< / BR>
where Ar is a halogen; R1is hydrogen or lower alkyl; R3- lower alkyl, possibly substituted by halogen, phenyl, unsubstituted or substituted lower alkyl, halogen, trifluoromethyl, lower alkoxy, halogen (lower) alkoxy, piperazinil, benzylpiperazine, lower arylpiperazines, lower alkoxypiperidine, the alkyl portion of which may be substituted by halogen, pyridyl or pyrimidinergic; X is a nitrogen atom or methine group; and Y and Z are independently a nitrogen atom or retinovoy group, which optionally may be additionally substituted lower alkyl group, or an acid additive salt having antifungal activity, and a pharmaceutical composition thereof. These compounds are produced by the interaction of the compounds II and III

< / BR>
4 c. and 25 C.p. f-crystals, 34 PL.

The invention relates to a derivative of asola used as antifungal therapeutic agents and to their use.

Various proizvodi is, however, not satisfactory in terms of their therapeutic effect from the point of view of antifungal activity spectrum antifungal action, side effects and pharmacokinetics.

Traditional antifungal drugs do not have a therapeutic effect and, moreover, there are many problems with side effects, pharmacokinetics, superinfection and acquired resistance to drugs.

To resolve these problems, it is clear that as therapeutics desirable compounds with a high degree of security, the best absorption in vivo and stronger antifungal activity.

The invention relates to a derivative azole formula (I)

< / BR>
where

Ar is disubstituted by halogen phenyl group;

R1is hydrogen atom or lower alkyl group;

R3represents lower alkyl, possibly substituted by halogen, phenyl, unsubstituted or substituted lower alkyl, halogen, trifluoromethyl, lower alkoxy, halogen (lower) alkoxy, piperazinil, benzylpiperazine, lower arylpiperazines, lower alkoxypiperidine, the alkyl portion of which may be semantization are a nitrogen atom or retinovoy group, which optionally may be additionally substituted lower alkyl group,

or kislotoustoichivam salts.

Further, the invention provides an antifungal drug, which includes a derivative azole represented by the formula (I) or its salt.

The compound of formula I or its salt according to the invention has one or more asymmetric carbon atoms in the molecule thus has two or more stereoisomers. Some of these stereoisomers as well as their mixture, are within the scope of the invention. As regards the optical isomers is preferred when the carbon that is attached to the substituted phenyl, Ar, and the carbon attached to R1have the R-configuration.

The compound of formula I or its salt according to the invention can be obtained, for example, by reaction of the compound of formula (II)

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where the values of the radicals are defined as above, with a compound of formula (III)

< / BR>
where the values of the radicals are defined as above, or its salt.

This reaction can usually be carried out in a solvent that does not inhibit the reaction. Examples of such a solvent may include: water; karafarin or dioxane; NITRILES, such as acetonitrile; aromatic hydrocarbons such as benzene, toluene or xylene; halogenated hydrocarbons such as dichloromethane, chloroform or 1,2-dichloroethane; ethers, such as ethyl acetate; amides, such as dimethylformamide, ndimethylacetamide or dimethylacetamide; urea derivatives, such as 1,3-dimethyl-2-imidazolidinone; etc. Solvent may be used both individually and in a mixture of solvents, taken in a suitable ratio.

Preferably, this reaction proceeded in the presence of a base such as a hydroxide of an alkali metal (e.g. lithium hydroxide, potassium hydroxide or sodium hydroxide), alkali metal hydride (for example, potassium hydride or sodium hydride), carbonate of alkaline metal (such as lithium carbonate, sodium bicarbonate, cesium carbonate, potassium carbonate or sodium carbonate), salt, organic acid (e.g. sodium acetate), alcoholate of an alkali metal (e.g. sodium methylate or of potassium tert-butylate), fluoride, tetrabutylammonium, bis(tri-n-butylstannyl)oxide, etc.

Instead of the compounds of formula III can be used in its salt with a metal (for example, an alkaline metal such as sodium or the used base is usually 0.001 to 100 equiv., preferably about 0.01-50 EQ. regarding the compounds of formula (II).

The amount of the compounds of formula (III) or its salt is 1-100 EQ., preferably about 1-50 EQ. regarding the compounds of formula (II).

The reaction temperature is not limited in a particular way, but can usually be approximately 0-150oC, preferably of about 10-120oC.

The reaction time is usually from several minutes to several tens of hours (e.g., from 5 minutes to 50 hours).

The compound of formula I according to the invention can also be obtained, for example, by reaction of the compound of formula (IV)

< / BR>
where the values of the radicals are defined as above, or its salt with the compound of the formula (V)

< / BR>
where the values of the radicals are defined as above, or its salt.

This reaction can usually be carried out in a solvent which does not affect the reaction. Examples of such solvents are: water; a ketone, such as acetone; sulfoxide such as dimethylsulfoxide; ethers such as diethyl ether, tetrahydrofuran or dioxane; a nitrile such as acetonitrile; aromatic hydrocarbons such as benzene, toluene or xylene; halogenated hydrocarbons, such ka the Tamid or dimethylacetamide; a derivative of urea such as 1,3-dimethyl-2-imidazolidinone; etc. They can be used both individually and in a mixture, taken in a suitable ratio.

Preferably, the reaction was carried out in the presence of a base such as alkali metal hydroxides (e.g. lithium hydroxide, potassium hydroxide or sodium hydroxide), alkali metal hydrides (e.g., potassium hydride or sodium hydride), carbonate of alkaline metal (such as lithium carbonate, sodium bicarbonate, cesium carbonate, potassium carbonate or sodium carbonate), salt, organic acid (e.g. sodium acetate), alcoholate of an alkali metal (e.g. sodium methylate or tetrabutyrate potassium), tetrabutylammonium etc.

The amount of the base is generally about 0.01-100 equiv., preferably about 0.01-50 EQ. with respect to the compound of formula (IV).

The amount of the compounds of formula (V) or its salt with respect to the compound of formula (IV) or its salt is 1-100 EQ., preferably about 1-50 EQ.

The reaction temperature is not specifically limited, but may be generally 0-150oC, preferably of about 10-120oC.

The reaction time is usually costal who I can also be used as a salt, and examples of such salts are pharmacologically acceptable salts, such as inorganic salts (for example, hydrochloride, hydrobromide, sulphates, nitrates or phosphates) and organic salts (for example, acetate, tartratami, citrates, fumarate, maleate, toluensulfonate or methansulfonate).

Examples of salts of the source material, including the aforementioned compounds of formulas III and IV are the same as those salts for the compounds of formula I.

The compound of formula I or its salt can be isolated from the reaction mixture by the known methods of separation and purification such as extraction, filtration, recrystallization, columnar chromatography and thin layer chromatography.

The compound of formula I or its salt can have at least two stereoisomer. Each of these isomers or each mixture contained in the scope of the invention, but, if desirable, each of the isomers can be synthesized separately. For example, a single isomer of the compounds of formula I can be obtained from each individual isomer of the starting compound of formula II or IV. When the product is a mixture of one or more isomers, they can be separated into individual isomers by conventional methods such as a method of obtaining salts of optically active acids (for example, camphorsulfonic acid S="ptx2">

Salts of the compounds of formula I can also be obtained by such method as the processing of these inorganic or organic acids of the compounds of formula I.

The compound of formula I or its salt, having low toxicity and significant antifungal activity with a wide antifungal spectrum of activity (for example, effective against Candida, Aspergillus or Cryptococcus) can be used for the prevention and treatment of fungal infections (like candidiasis, aspergillosis or cryptococcosis) in mammals (e.g. humans, animals or birds). The compound of formula I or its salt can be also used as an antifungal drug in agriculture.

The compound of formula I or its salt can be safely administered as oral and parenteral man in the form of pharmaceutical compositions (e.g., powder, granules, tablets or capsules), parenteral preparations (for example, injections, external preparations, such as nose or skin, suppositories, such as rectal or vaginal, and so forth) per se or in a mixture with the corresponding pharmacologically acceptable carriers, excipients or diluents.

These drugs can the drug.

For example, the compound of formula I or its salt according to the invention can be in the form of injections, such as water injection, comprising dispersing agent (for example, Tween 60 [Atlas Power, USA], MCO 60 [Nikko Chemicals, Japan], carboxymethylcellulose and sodium alginate), a stabilizer (for example, methylparaben, propylparaben, benzyl alcohol or chlorobutanol), isotonic agent (e.g. sodium chloride, glycerol, sorbitol or glucose), and the like, or such as injection is obtained by dissolving, suspendirovanie or emulsified in a vegetable oil (such as olive oil, sesame (sesame) oil, peanut oil, cottonseed oil or corn oil), propylene glycol, and the like.

When getting drugs for oral administration of compound I or its salt according to the invention is pressed under pressure together with, for example, fibers (for example, lactose, sugar or starch), loosening agents (for example, starch or calcium carbonate), binders (e.g. starch, arable rubber, carboxymethylcellulose, polyvinylpyrrolidone or hydroxypropylcellulose), a lubricant (e.g. talc, magnesium stearate or polyethylene glycol 6000 and the like or, if necessary, under a layer (in sootvetstvuyushiye in the gut. Examples are, for example, hypromellose, ethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, polyoxyethyleneglycol, Tween 80, Pluronic F80, acetate phthalate cellulose phthalate of hydroxypropylmethylcellulose, acetate succinate of hydroxymethylcellulose, Eudoragit (Rohm, West Germany; a copolymer of methacrylic acid and acrylic acid) and dyes such as titanium oxide and red iron oxide.

In the case of the preparation for external use of the compound of formula I or its salt according to the invention can be, for example, in the form of solid, semi-solid or liquid preparation made by the known per se method. For example, in the case of a solid preparation, the compound of formula I or its salt is used directly or in the form of a mixture with fillers (for example, glucose, mannitol, starch or microcrystalline cellulose), a thickener (e.g., natural rubbers, cellulose derivatives or polymers of acrylic acid), etc. to obtain a powder composition. In the case of a liquid preparation procedure is almost the same as in the case of injection from getting oily or aqueous suspension. In the case of a semi-solid preparation is preferred aqueous or oily gel or ointment. All this mogiana acid or sodium hydroxide), antiseptics (e.g., p-hydroxybenzoate, chlorobutanol or benzalkonium chloride) and the like. For example, for sterilization or disinfection of the skin or mucous membranes is possible to use ointment, prepared on the basis of 0.1-100 mg of the drug per 1 g of the used petroleum jelly or lanolin as a base material.

In the case of suppositories compounds according to the invention I or its salt can be produced by a known method per se in the form of oil or water suppositories in solid, semisolid, or liquid form. Examples of materials used for oil base are glycerides of high fat acids (for example, cocoa butter, Witepsols (Dinamite-Nobell), medium-chain fatty acids (for example, Migriol (Dynamite-Nobell), vegetable oil (e.g. sesame oil, soybean oil or cotton oil) and the like. Examples of materials used for water bases are polyethylene glycol and propylene glycol, and examples of materials for water gels are natural rubber, cellulose derivatives, vinyl polymers and polymers of acrylic acid.

Doses can vary depending on the degree of infection and the destination path, in the case of adult patients (body weight 50 kg) for the treatment of candidiasis.

In the case of use as an antifungal agent for agricultural crops compound of formula I or its salt is dissolved or dispersed in a suitable liquid carrier (e.g., solvent), or a mix, or absorb with an appropriate solid carrier (e.g. a diluent or filler), followed, if necessary, by adding an emulsifier, a suspending agent, lubricant, stabilizer and so on, obtaining medication, such as emulsion, hydrated agent, powders, granules. Such preparations can be obtained by a known method per se. The amount of compounds of formula I or its salts, for example in case of illness rice pest, 25-150 g, preferably 40-80 g ar infected rice fields.

Examples used liquid carrier is water, alcohols (e.g. methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol or ethylene glycol), ethers (e.g. dioxane or tetrahydrofuran), aliphatic hydrocarbons (e.g. kerosene, lamp oil, or residual oil), aromatic hydrocarbons (e.g. benzene or toluene), halogenated hydrocarbons (e.g. methylene chloride or chloroform), acid amides (napoleonica or propionitrile) and the like. They can be used individually or as mixtures thereof in an appropriate ratio.

Examples of the solid carrier are vegetable powder (for example, powder, soybean powder, tobacco or wheat flour), mineral powder (for example, kaolin or bentonite), alumina, sulfur powder, activated carbon, etc. They can be used both individually and in a mixture at an appropriate ratio.

The invention is illustrated further by the following reference examples and working examples.

1H-NMR spectra were measured on the spectrometer type Varian Gemini 200 (200 MHz) using tetramethylsilane as an internal standard. All values are given in ppm. For mixed solvents figures given in parentheses indicate the volume fraction of each solvent in the mixture. The symbol "%" means % by weight unless given other explanations.

Symbols used in the examples have the following meaning: s: singlet, d: doublet; t: triplet; k: quadruplet; dd: double doublet, m: multiplet; br: extended; j: constant signal; 1H-NMR:1H-NMR; IRmax: IRmax; cm-1: cm-1; neat: clean.

Referential example 1. 2-[(1R)-1-(3,4,5,6-Tetrahydro-2H-Piran - 2-yl)ox is sulfonate pyridinium dissolved in 600 ml of ethanol and the solution stirred at 55oC for 1 h, the Reaction solution is concentrated under reduced pressure. The residue is dissolved in 1 l of ethyl acetate and the resulting solution washed with water (2200 ml). The aqueous layer was extracted with ethyl acetate (2100 ml). The organic layers are combined, washed with saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure. The residue is purified using chromatography on silica gel (eluent - hexane: ethyl acetate = 10: 1 to 8:1 to 3:1) to obtain 31.5 g of (1R)-1-[2-(2,4-differenl)-2-oxiranyl]ethanol as a pale yellow oil.

1H-NMR (CDCl3) : 1,14-of 1.23 (3H, m), 1,77, 2,22 (1H), 2,80, 2,92 (1H), 3.27 to of 3.32 (1H), 4,00-4,20 (1H, m), 6.75 in-6,94 (2H, m), of 7.36-of 7.48 (1H, m).

Referential example 2. (1R)-1-[2-(2,4-Differenl)-2-oxiranyl]ethanol (31,5 g) and 40 g of 3,5-dinitrobenzotrifluoride dissolved in 500 ml of methylene chloride, and under ice cooling is added dropwise to 24.1 ml of trimethylamine. The reaction solution is stirred at room temperature for 3.5 h, washed with 150 ml of water and then 150 ml of a 5% aqueous solution of bicarbonate, dried over magnesium sulfate and concentrate under reduced pressure. The crystals are separated by filtration and washed with methylene chloride. The mother liquor and wash water are combined and evaporated under demoted is really by filtration and recrystallized from a mixture of 25 ml of ethyl acetate and 250 ml of methanol to obtain 28,7 g [(1R)-1-[(2R)-2-(2,4-differenl)- 2-oxiranyl]ethyl]-3,5-dinitrobenzoate in the form of colorless needles.

T. pl. 104-107oC (recrystallization from ethyl acetate-hexane).

1H-NMR (CDCl3) : of 1.46 (3H, dd, J = 6,6 Hz, J = 1,2 Hz), 3,01 (1H, d, J = 4,6 Hz), 3,23 (1H, d, J = 4,6 Hz), 5,33(1H, q, J = 6,6 Hz), 6,85-7,07 (2H, m), 7,54 (1H, m), 9,13 (2H, d, J = 2,2 Hz), the 9.25 (1H, t, J = 2,2 Hz).

Reference example 3. [(1R)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethyl]- 3,5-dinitrobenzoate (50 g) is dissolved in 2 l of methanol and, at room temperature, added dropwise 255 ml of 1N. the sodium hydroxide solution. The reaction solution is stirred for 1 h at room temperature and neutralized 127 ml of 1N. of hydrochloric acid. The methanol is removed under reduced pressure, then to the residue was added 1 l of ethyl acetate and 200 ml of water and the mixture extracted with ethyl acetate. The organic extract was washed with 200 ml saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure. The residue is purified using chromatography on silica gel (eluent - hexane:ethyl acetate = 3:1) to obtain 25 g of (1R)-1-[(2R)-2-(2,4-differenl)- 2-oxiranyl]ethanol as a pale yellow oil.

1H-NMR (CDCl3) : of 1.17 (3H, dd, J = 6,6 Hz, l,2H), 2,05 (1H, br), 2,80 (1H, d, J = 5,2 Hz), 3,30 (1H, d, J = 5,2 Hz), 4,01-4,17 (1H, m), 6.75 in-6,93 (2H, m), of 7.36-of 7.48 (1H, m).

Reference example 4. K the solution of 16.1 g (1R)-1-[(2R)-2-(2,4-Differenl)- 2-oxiranyl] ethanol in 320 ml of tetracarboxylate and the mixture is stirred for 6 h in an argon atmosphere at room temperature. To the reaction solution was added 800 ml of ethyl acetate and 500 ml of water for fractionation, and the aqueous layer was extracted with 200 ml of ethyl acetate. The organic layers are combined and washed with water and saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated. The residue is purified using chromatography on silica gel (eluent - hexane:ethyl acetate = 15: 1 to 7:1) to give 19.2 g of [1S)-1-[(2R)-2-(2,4-differenl)-2 - oxiranyl]ethyl]benzoate as a colorless oil.

1H-NMR (CDCl3) : of 1.37 (3H, d, J = 6,6 Hz), 2,90 (1H, d, J = 5,2 Hz), or 3.28 (1H, d, J = 5,2 Hz), are 5.36 (1H, q, J = 6,6 Hz), 6,74-6,94 (2H, m), 7,38-of 7.60 (4H, m), 7,94 shed 8.01 (2H, m).

IRneamaxtcm-1: 1725, 1615, 1600, 1505, 1450, 1425.

[1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethyl]benzoate (15.9 g) was dissolved in 800 ml of methanol. Under ice cooling, add 28% methanol solution of sodium methylate (12.9 ml), and the reaction solution stirred at room temperature for 6 hours To the reaction solution are added to 63.2 ml of 1N. hydrochloric acid and the solvent is removed by evaporation under reduced pressure.

The residue is purified using chromatography on silica gel (eluent - hexane: ethyl acetate = 6: 1 to 2:1) to give 9.7 g of (1S)-1[(2R)-2-(2,4-differenl)-2-oxiranyl}ethanol as colourless 4 Hz), 6,77-to 6.95 (2H, m), 7,34 (1H, m).

IRneamaxtcm-1= 3420, 2980, 1615, 1600, 1500, 1425.

Reference example 5. To a solution of (1S)-1-[(2R)-2-(2,4-Differenl)- 2-oxiranyl]ethanol in 15 ml of dichloromethane is added in nitrogen atmosphere of 0.51 ml diisopropylethylamine at -78oC and then 0,49 ml of anhydride triftormetilfullerenov acid dropwise within 3 minutes, the Mixture was stirred at -78oC 20 min, then at -20oC 20 min and concentrated to 9 ml at -10oC. the Concentrate is subjected to a flash chromatography column using silica gel (3.2 x 4 cm), elwira with dichloromethane-hexane (1:1). The desired fraction is concentrated to 3 ml, the residue added to a solution of sodium salt of 1-(4-triptoreline)-2(1H, 3H)-imidazolone obtained from 606 mg of 1-(4-triptoreline)-2(1H, 3H)-imidazolone, 3 ml of dimethylformamide and 85 mg of 60% sodium hydride in oil, if -10oC and stirring for 10 minutes the Reaction solution is further stirred at 0oC for 20 minutes is Added to the reaction solution, water (30 ml) and the mixture is extracted with 30 ml of ethyl acetate four times. An ethyl acetate extract is washed with twice 20 ml of water and then once with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and udayi on silica gel (eluent - hexane: ethyl acetate = 3:1 to 2:1 to 1:1) to obtain 362 g of 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 3-(4-triptoreline)-2(1H, 3H)- imidazolone and 209 mg (2R)-2-(2,4-differenl)-2-[(1R)-1-[1-(4-triptoreline)- 2-imidazolidone]ethyl]oxirane.

1-[(1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl]- 3-(4-triptoreline)-2(1H,3H)imidazole, colorless prisms. So pl. 135-136oC.

1H-NMR (CDCl3) : of 1.37 (3H, d, J = 7,2 Hz), 2,72 (1H, d, J = 4,4 Hz), 2,82 (1H, d, J = 4,4 Hz), 5,09 (1H, q, J = 7,2 Hz), 6,50 (1H, d, J = 3,2 Hz), only 6.64 (1H, d, J = 3,2 Hz), 6,80-6,97 (2H, m), 7,35 is 7.50 (1H, m), of 7.69 (2H, d, J = 8,4 Hz), 7,82 (2H, d, J = 8,4 Hz).

IRkbrmaxcm-1: 3010, 1684, 1616, 1523.

Calculated, %: C 58,54; H 3,68; N 6,83.

C20H15F5N5O2.

Found, %: C 58,80; H 3,90; N For 6.81.

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-(4-triptoreline)- 2-imidazolidone]ethyl]oxirane, colorless oil.

1H-NMR (CDCl3) : of 1.46 (3H, dd, J = 6,6, and 1.6 Hz), 2,89 (1H, d, J = 4,8 Hz), and 3.16 (1H, d, J = 4,8 Hz), 5,24 (1H, q, J = 6,6 Hz), 6,70-6,91 (4H, m), 7,22-7,40 (1H, m), to 7.50 (2H, d, J = 8,4 Hz), of 7.70 (2H, d, J = 8,4 Hz).

IRneamaxtcm-1: 3010, 1620, 1616, 1599, 1547.

SIMS (m/z): 411 (M+H)+.

Reference example 6. In the same manner as in reference example 5 based on 423 mg (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 207 mg of 1-morpheel)-2,3-epoxy-1-methylpropyl] -3-methyl - 2(1H,3H)-imidazolone in the form of a colorless oil.

1H-NMR (CDCl3) : of 1.40 (3H, dd, J = 6,4, and 1.4 Hz), 2,90 (1H, d, J = 5,4 Hz), 3,23 (1H, d, J = 5,4 Hz), 3,37 (3H, s), is 5.18 (1H, d, J = 6,4 Hz), 6.48 in (1H, d, J = 1,6 Hz), 6,59 (1H, J = 1,6 Hz), 6.75 in-6,98 (2H, m), 7,41-to 7.59 (1H, m).

IRneamaxtcm-1: 2980, 1734, 1616, 1600, 1539, 1506.

SIMS (m/z): 281 (M+H)+.

Reference example 7. By the same method as in reference example 5, from 1,95 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 1.39 g of 1-(4-forfinal)-2(1H, 3H)-imidazolone was obtained 1.10 g of 1-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl]-3-(4-forfinal)- 2(1H,3H)-imidazolone and 0.88 g of (2R)-2-(2,4-differenl)-2-[(1R)-1-[1 - 4-forfinal)-2-imidazolidone]ethyl of oxirane.

1-[(1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl] - 3-(4-forfinal)-2(1H,3H)-imidazolone, colorless oil.

1H-NMR (CDCl3) : of 1.37 (3H, d, J = 7,2 Hz), 2,70 (1H, d, J = 4,8 Hz), of 2.81 (1H, d, J = 4,8 Hz), 5,07 (1H, d, J = 7,2 Hz), 6,44 (1H, d, J = 3,2 Hz), of 6.52 (1H, d, J = 3,2 Hz), 6,79-6,98 (2H, m), 7,02-7,20 (2H, m), 7,35 is 7.50 (1H, m), 7,50-to 7.68 (2H, m).

IRneamaxtcm-1: 3130, 3050, 2985, 1736, 1693, 1618, 1600, 1512.

SIMS (M/z): 361 (M+H)+.

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-(4-forfinal)- 2-imidazolidone] ethyl]oxirane, colorless oil.

1H-NMR (CDCl3) : the 1.44 (3H, dd, J = 6,4, and 1.6 Hz), 2,88 (1H, d, J = 4,8 Hz), 3,14 (1H, d, J = 4,8 Hz), 5,16 (1H, q, J = 6,4 Hz), 6,65-to 6.80 (4H, m), 7,01-7,19 (2H, m), 7,20-7,38 (3H, m).

1-[1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl]- 3-(2,4-differenl)-2(1H,3H)-imidazolone, pale yellow oil.

1H-other (CDCl3) : to 1.38 (3H, d, J = 7,2 Hz), 2,72 (1H, d, J = 4,6 Hz), and 2.83 (1H, d, J = 4,6 Hz), is 5.06 (1H, q, J=7,2 Hz), 6,44 (2H, s), 6,78-7,03 (4H, m), 7,42 (1H, m), 7,60 (1H, m).

IRneamaxtcm-1: 1699, 1616, 1519, 1430, 1267.

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-(2,4-differenl)- 2-imidazolidone]ethyl]oxirane, pale yellow oil.

1H-NMR (CDCl3) : of 1.39 (3H, d, J= 6,5 Hz), 2,87 (1H, d, J = 5 Hz), 3,13 (1H, d, J = 5 Hz), 5,4(1H, q, J = 6,5 Hz), 6,62-7,05 (6H, m), 7,15 was 7.45 (2H, m).

IRneamaxtcm-1: 1705, 1616, 1549, 1520, 1462, 1435.

Reference example 9. By the same method as in reference example 5, on the basis of 1.35 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 963 mg of 4-(4-forfinal)-3(2H,4H)-1,2,4-triazolone receive 583 g of 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methyl-propyl] -4-(4-forfinal)- 3(2H,4H)-1,2,4-triazolone in the form of colorless needles.

So p-6,91 (2H, m), 7,08-7,22 (2H, m), 7,25-7,51 (3H, m), 7,63 (1H, s).

IRKBrmaxcm-1: 3128, 3068, 2995, 1693, 1618, 1514, 1502, 1396.

Calculated, %: C 59,84; H 3,91; N 11,63.

C18H14F3N3O2.

Found, %: C 59,85; H 3,93; N 11,74.

Reference example 10. By the same method as in reference example 5, on the basis of 1.66 g of (1S)-1-(2R)-2-(2,4-Differenl)-2-oxiranyl-ethanol and 1.26 g of 1-(methoxyphenyl)-2(1H, 3H)-imidazolone get 1-(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl-3-(4-methoxyphenyl)- 2(1H,3H)-imidazole 617 mg in the form of colorless prisms.

So pl. 150-151oC.

1H-NMR (CDCl3) : of 1.36 (3H, d, J = 7,2 Hz), 2,70 (1H, d, J = 4,8 Hz), of 2.81 (1H, d, J = 4,8 Hz), 3,82 (3H, s), 5,07 (1H, q, J = 7,2 Hz), 6,41 (1H, d, J= 3 Hz), of 6.49 (1H, d, J = 3Hz), 6,78-to 6.95 (2H, m), 6,94 (2H, d, J = 9 Hz), 7,35 is 7.50 (1H, m), 7,49 (2H, d, J = 9 Hz).

Calculated, %: C 64,51; H To 4.87; N 7,52.

C20H18F2N2O3.

Found, %: C 64,26; H Equal To 4.97; N 7,46.

IRKBrmaxcm-1: 3250, 3010, 1693, 1620, 1514, 1504, 1441.

Reference example 11.

By the same method as in reference example 5, on the basis of 1.73 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl] ethanol and of 1.32 g of 4-(4-methoxyphenyl)-3(2H, 4H)-1,2,4-triazolone get 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methyl-propyl] -4-(4-methoxyphenyl)- 3(2H,4H)-1,2,4-triazolo 869 mg in 5 (1H, q, J = 7 H), 6,74-of 6.90 (2H, m), of 6.96 (2H, d, J = 9,2 Hz), 7,28-7,42 (1H, m), of 7.36 (2H, d, J = 9,2 Hz), to 7.59 (1H, s).

IRneamaxtcm-1: 3100, 3005, 2920, 1699, 1616, 1601, 1556, 1519.

SIMS (m/z): 374 (M+H)+.

Referential example 12. By the same method as in reference example 5 according to 1.36 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and of 1.32 g of 1-(4-trifloromethyl)-2(1H,3H)-imidazolone get 1-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methyl-propyl] - 3-(4-trifloromethyl)-2(1H,3H)-imidazole (0,60 g) and 0.46 g of (2R)-2-(2,4-differenl)-2-[(1R)-1-[1-(4-trifloromethyl)- 2-imidazolidone]ethyl]oxirane.

1-[(1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl]- 3-(4-trifloromethyl)-2(1H,3H)-imidazolone - colorless crystals.

So pl. 99-100oC.

1H-NMR (CDCl3) : of 1.37 (3H, d, J = 7,2 Hz), 2,71 (1H, d, J = 4,8 Hz), 2,80 (1H, d, J = 4,8 Hz), 5,07 (1H, q, J = 7,2 Hz), 6,46 (1H, d, J = 3,2 Hz), 6,56 (1H, d, J = 3,2 Hz), 6,80-of 6.96 (2H, m), 7,28 (2H, d, J = 9 Hz), 7,40 (1H, m), to 7.67 (2H, d, J = 9 Hz).

IRKBrmaxcm-1: 1682, 1620, 1606, 1516, 1433, 1353.

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-(4-trifloromethyl)- 2-imidazolidone]ethyl]oxirane - pale-yellow oil.

IRneamaxtcm-1: 1616, 1558, 1541, 1516, 1458, 1261.

1H-NMR (CDCl3) : of 1.45 (3H, dd, J = 6,6 Hz, J = 1,6 Hz), 2,90 (1H, d, J = 5 Hz), 3,14 (1H, d, J = 5 Hz), 5,19 (1H, q, J = 6,6 Hz is (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and of 1.87 g of 4-(triptoreline)-3(2H,4H)-1,2,4-triazolone get 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-(4-triptoreline)-3(2H, 4H)-1,2,4-triazole (1.26 g) as colorless crystals.

1H-NMR (CDCl3) : to 1.48 (3H, d, J = 7,4 Hz), 2,89 (1H, d, J = 4,6 Hz), and 3.16 (1H, d, J = 4,6 Hz), of 4.95 (1H, q, J = 7,2 Hz), 6,74-of 6.90 (2H, m), 7,28-7,42 (1H, m), of 7.64-7,86 (5H, m).

IRKBrmaxcm-1: 1700, 1620, 1390, 1320, 1110.

Calculated, %: C 55,48; H 3,43; N 10,22.

C19H14F5N3O2.

Found, %: C 55,56; H 3,43; N 10,15.

Reference example 14. By the same method as in reference example 5 based on 2,49 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 2.52 g of 2-(4-triptoreline)-3(2H, 4H)-1,2,4-triazolone receive 4-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 2-(4-triptoreline)-3(2H, 4H)-1,2,4-triazole (1.13 g) and 618 mg (2R)-2-(2,4-differenl)-2-[(1R)-1-[1-(4-triptoreline)-1H - 1,2,4-triazole-5-yloxy]ethyl]oxirane.

4-[1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl] - 2-(4-triptoreline)-3(2H,4H)-1,2,4-triazole, colorless prisms.

So pl. 164-165oC.

1H-NMR (CDCl3) : the 1.44 (3H, d, J = 7,2 Hz), is 2.74 (1H, d, J = 4,2 Hz), 2,78 (1H, d, J = 4,2 Hz), 5,02 (1H, q, J = 7,2 Hz), 6,80-7,01 (2H, m), 7,35-7,51 (1H, m), of 7.64 (1H, s), of 7.70 (2H, d, J = 8,8 Hz), 8,18 (2H, d, J = 8,8 Hz).

IRKBrmaxcm-1: 3060, 1722, 1619, 1601, 1564, 1524.

Calculated, %: C 55,48; H 3,43; N 10,22.

C19H14F5N

1H-NMR (CDCl3) : of 1.53 (3H, dd, J = 6,6, and 1.6 Hz), to 2.94 (1H, d, J = 4,8 Hz), up 3.22 (1H, d, J = 4,8 Hz), lower than the 5.37 (1H, q, J = 6,6 Hz), 6.75 in-6,98 (2H, m), 7,38-7,52 (1H, m), 7,69 (1H, s), of 7.70 (2H, d, J = 8,4 Hz), the 7.85 (2H, d, J = 8,4 Hz).

IRneamaxtcm-1: 3050, 1618, 1599, 1558, 1540.

Reference example 15. By the same method as in reference example 5 according to 1.36 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and of 1.33 g of 4-(4-trifloromethyl)-3(2H, 4H)-1,2,4-triazolone get 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl]- 4-(4-trifloromethyl)-3(2H, 4H)-1,2,4-triazole (1.45 g) as colorless prisms. So pl. 103-106oC.

1H-NMR (CDCl3) : to 1.48 (3H, d, J = 7 Hz), 2,88 (1H, d, J = 4,8 Hz), and 3.16 (1H, d, J = 4,8 Hz), 4,94 (1H, q, J = 7 Hz), 6,72-6,92 (2H, m), 7,25 was 7.45 (3H, m), 7,56 (2H, d, J = 9,2 Hz), 7,66 (1H, s).

IRKBrmaxcm-1: 3136, 3082, 1697, 1620, 1562, 1514, 1430, 1392, 1257, 1222.

Reference example 16. By the same method as in reference example 5 based on 0,83 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and of 0.83 g of 1-(4-isopropylphenyl)-2(1H, 3H)-imidazolone get 1-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 3-(4-isopropylphenyl)-2(1H,3H)-imidazole (0.25 g) and 0.22 g of (2R)-2-(2,4-differenl)-2-[(1R)-1-[1-(4-isopropylphenyl)- 2-imidazolidone]ethyl]oxirane.

1-[(1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl] - 3-(4-isopropylphenyl is 36 (3H, d, J = 7,4 Hz), 2,70 (1H, d, J = 5 Hz), of 2.81 (1H, d, J = 5 Hz), 2,92 (1H, quintet, J = 7,0 Hz), to 5.08 (1H, q, J = 7,4 Hz), 6.42 per (1H, d, J = 3,2 Hz), is 6.54 (1H, d, J = 3,2 Hz), 6,80-6,93 (2H, m), 7,27 (2H, d, J = 8,6 Hz), 7,35-of 7.48 (1H, m), 7,52 (2H, d, J = 8,6 Hz).

IRKBrmaxcm-1: 2950, 1680, 1515, 1495, 1420.

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-(4-isopropylphenyl)- 2-imidazolidone]ethyl]oxirane, colorless oil.

1H-NMR (CDCl3) : of 1.30 (6H, d, J = 7 Hz), USD 1.43 (3H, d, J = 6,6 Hz), 2,88 (1H, d, J = 5,0 Hz), 2,97 (1H, q, J = 7,0 Hz) and 3.15 (1H, d, J = 5,0 Hz), 5,14 (1H, d, J = 6,6 Hz), 6,67-PC 6.82 (4H, m), 7,26 (4H, s), 7,22-to 7.35 (1H, m).

Reference example 17. By the same method as in reference example 5 according to 1.36 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 1.07 g of 4-(2,4-differenl)-3(2H, 4H)-1,2,4-triazolone get 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] -4-(2,4-differenl)- 3(2H, 4H)-1,2,4-triazole (1.20 g) as a colourless oil.

1H-NMR (CDCl3) : to 1.48 (3H, d, J = 7,2 Hz), 2,89 (1H, d, J = 4,6 Hz), 3,18 (1H, d, J = 4,6 Hz), 4,94 (1H, q, J = 7,2 Hz), 6,76-6,94 (2H, m), 6,95-7,10 (2H, m), 7,28-7,42 (1H, m), 7,50-the 7.65 (1H, m), 7,58 (1H, d, J = 2,2 Hz).

IRneamaxtcm-1: 1716, 1616, 1558, 1519, 1427, 1403, 1270.

Reference example 18. By the same method as in reference example 5, on the basis of of 2.27 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and of 1.80 g of 2-(4-forfinal)-3(2H, 4H)-1,2,4-triazolone receive 4-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] -2-(oxiran.

4-[(1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl] - 2-(4-forfinal)-3(2H,4H)-1,2,4-triazole, colorless prisms. So pl. 163-164oC.

1H-NMR (CDCl3) : USD 1.43 (3H, d, J = 7,2 Hz), 2,73 (1H, d, J = 4,2 Hz), 2,77 (1H, d, J = 4,2 Hz), free 5.01 (1H, q, J = 7,2 Hz), 6,82-7,01 (2H, m), 7,12 (2H, t, J = 8,8 Hz), 7,35 is 7.50 (1H, m), 7,60 (1H, s), of 7.96 (2H, dd, J = 8,8, 4,6 Hz).

IRKBrmaxcm-1: 3060, 1714, 1620, 1603, 1562, 1512.

Calculated, %: C 59,84; H 3,91; N 11,63.

C18H14F3N3O2.

Found, %: C To 59.51; H 3,83; N 11,83.

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-(4-forfinal)-1H-1,2,4-triazole - 5-yloxy]ethyl]oxirane, colorless oil.

1H-NMR (CDCl3) : 1,50 (3H, dd, J = 6,6, and 1.6 Hz), with 2.93 (1H, d, J = 4,8 Hz), 3,20 (1H, d, J = 4,8 Hz), 5,27 (1H, q, J = 6,6 Hz), 6,76-6,98 (2H, m), 7,13 (2H, t, J = 8,2 Hz), 7,30-7,49 (1H, m), 7,63 (2H, dd, J = 4,6, and 8.2 Hz), to 7.64 (1H, s).

IRneamaxtcm-1: 3077, 2995, 1618, 1601, 1543.

Reference example 19. By the same method as in reference example 5 based on 681 mg (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.0 g of 4-[4-(4-benzyl-1-piperazinil)phenyl]-3(2H,4H)-1,2,4-triazolone get 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-[4-(4-benzyl-1-piperazinil)phenyl]-3(2H,4H)-1,2,4-triazole (293 mg) as colorless powder.

1H-NMR (CDCl3) : of 1.45 (3H, d, J = 7 Hz), 2,61 (4H, t, J = 4,8 Hz), 2,87 (1H, d, J = 4,8 Hz), and 3.16 (1H the example 20. By the same method as in reference example 5 based on 1,72 g of (1S)-1-1(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 1.68 g of 4-(4-isopropylphenyl)-3(2H, 4H)-1,2,4-triazolone receive a mixture of about 1:1 (0,89 g), 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl]-4-(4-isopropylphenyl)-3(2H, 4H)-1,2,4-triazolone and (1R)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol.

1H-NMR (CDCl3) : of 1.16 (dd, J = 6,6, 1,0 Hz), 1,25 (d, J = 6,8 Hz) of 1.46 (d, J = 7 Hz), 1,78 (d, J = 8 Hz), and 2.79 (d, J = 5 Hz), 2,88 (d, J = 5 Hz), to 2.94 (q, J = 6,8 Hz), and 3.16 (d, J = 5 Hz), 3,30 (d, J = 5 Hz), was 4.02-4,17 (m), 4,96 (q, J = 7 Hz), 6.73 x-6,92 (m), 7,27 was 7.45 (m), 7.62mm (s).

Reference example 21. By the same method as in reference example 5 according to 1.41 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and of 1.30 g of 1-(4-triptoreline)-5(1H, 4H)-tetrazole get 1-[1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-(4-triptoreline)-5(1H,4H)-tetrazole (1,38 g) and has 0.168 g (2R)-2-(2,4-differenl)-2-[(1R)- 1-[1-(4-triptoreline)-1H-tetrazol-5-yloxy]ethyl]oxirane.

1-[(1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl]- 4-(4-triptoreline)-5(1H,4H)-tetrazole, colorless oil.

1H-NMR (CDCl3) : to 1.61 (3H, d, J = 7,2 Hz), with 2.93 (1H, d, J = 4,6 Hz), and 3.16 (1H, d, J = 4,6 Hz), equal to 4.97 (1H, q, J = 7,2 Hz), 6,72-6,94 (2H, m), 7.23 percent-7,40 (1H, m), of 7.75 (2H, d, J = 8,4 Hz), 8,13 (2H, d, J = 8,4 Hz).

IRneamaxtcm-1: 3100, 1734, 1618, 1522, 1508, 1429.

SIMS (m/z): to maintain the oil.

1H-NMR (CDCl3) : to 1.59 (3H, dd, J = 6,6, and 1.6 Hz), 2,98 (1H, d, J = 4,6 Hz), 3,23 (1H, d, J = 4,6 Hz), of 5.39 (1H, q, J = 6,6 Hz), 6.75 in-6,98 (2H, m), 7,32-7,49 (1H, m), 7,80 (2H, d, J = 9 Hz), 7,82 (2H, d, J = 9 Hz).

SIMS (m/z): 413 (M+H)+.

Reference example 22. By the same method as in reference example 5, on the basis of 0.50 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 0.72 g of 1-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -2(1H, 3H)-imidazolone get 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -2-(1H, 3H)-imidazolone (0.21 g) and 0.14 g of (2R)-2-(2,4-differenl)-2-[(1R)-1-1-[4-(2,2,3,3- tetrafluoropropoxy)phenyl]-2-imidazolidone]ethyl]oxirane.

1-[(1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl] - 3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2(1H,3H)-imidazolone.

1H-NMR (CDCl3) : of 1.36 (3H, d, J = 7,2 Hz), 2,70 (1H,d, J = 4,7 Hz), of 2.81 (1H, d, J = 4,7 Hz), 4,36 (2H, t, J = 12 Hz), 5,07 (1H, q, J = 7,2 Hz), the 6.06 (1H, tt, J = 4,8, 53 Hz), to 6.43 (1H, d, J = 3 Hz), 6,51 (1H, d, J = 3 Hz), 6,79-7,02 (4H, m), 7,26-7,47 (1H, m), 7,52-of 7.60 (2H, m).

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-4-(2,2,3,3- tetrafluoropropoxy)phenyl]-2-imidazolidone]ethyl oxirane.

1H-NMR (CDCl3) : USD 1.43 (3H, d, J = 6,6 Hz), 2,86 (1H, d, J = 5,2 Hz), 3,14 (1H, d, J = 5,2 Hz), 4,32-4,47 (2H, m), 5,19 (1H, q, J = 6,6 Hz), 6,09 (1H, tt, J = 4,8, 53 Hz), 6,72-6,83 (4H, m), 6.90 to-7,02 (2H, m), 7.24 to 7,47 (3H, m).

Reference example 23. By the same method as in reference example 5 based on 543 mg (1S)-1-[(scientists according to the method, described in Journal of Medicinal Chemistry, vol.27, p. 894 (1984), get 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl] -4-[4-[4-(4-methoxyphenyl)-1-piperazinil] phenyl] -3(2H, 4H)- 1,2,4-triazole (373 mg) as colorless prisms. So pl. 175-176oC.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7,2 Hz), 2,88 (1H, d, J = 4,8 Hz), and 3.16 (1H, d, J = 4,8 Hz), 3,17-3,30 (8H, m), with 3.79 (3H, s), 4,96 (1H, q, J = 7,2 Hz), 6.73 x-of 6.96 (2H, m), 6.87 in (2H, d, J = 9,2 Hz), of 6.96 (2H, d, J = 9,2 Hz), 7,01 (2H, d, J = 8,8 Hz), 7,34 (2H, d, J = 8,8 Hz), 7.24 to 7,41 (1H, m), 7,58 (1H, s).

Calculated, %: C 65,28; H 5,48; N 13,13.

C29H29F2N5O3.

Found, %: C 65,30; H 5,50; N 13,03.

Reference example 24. By the same method as in reference example 5, on the basis of 1.2 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 1.1 g of 4-(3-triptoreline)-3(2H, 4H)-1,2,4-triazolone get 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-(3-triptoreline)-3(2H, 4H)-1,2,4-triazole of 0.85 g) as colorless powder.

1H-NMR (CDCl3) : of 1.47 (3H, d, J = 7 Hz), 2,89 (1H, d, J = 4,6 Hz), and 3.16 (1H, d, J = 4,6 Hz), of 4.95 (1H, q, J = 7Hz), 6,75-of 6.90 (3H, m), 7,28 was 7.45 (2H, m), 7,73 (1H, s), 7,71-of 7.82 (2H, m).

Reference example 25. By the same method as in reference example 5 based on 1,43 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.03 g of 1-(4-forfinal)-5(1H, 4H)-tetrazole get 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl]-4-(4-a.

1-(1R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl - 4-(4-forfinal)-5(1H,4H)-tetrazole, colorless oil.

1H-NMR (CDCl3) : to 1.60 (3H, d, J = 7,2 Hz), with 2.93 (1H, d, J = 4,4 Hz), 3,17 (1H, d, J = 4,4 Hz), is 4.93 (1H, q, J = 7,2 Hz), 6.75 in-6,92 (2H, m), 7,10-7,40 (3H, m), 7,82-to 7.99 (2H, m).

SIMS (m/z): 363 (M+H)+.

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-(4-forfinal)-1H-tetrazol - 5-yloxy]ethyl]oxirane, colorless oil.

1H-NMR (CDCl3) : of 1.56 (3H, dd, J = 6,6, and 1.6 Hz), 2,96 (1H, d, J = 4,6 Hz), 3,20 (1H, d, J = 4,6 Hz), 5,31 (1H, q, J = 6,6 Hz), 6,74-of 6.96 (2H, m), 7.23 percent (2H, t, J = 9 Hz), 7,30-7,49 (1H, m), the 7.65 (2H, dd, J = 4,6 Hz).

SIMS (m/z): 363 (M+H)+.

Reference example 26. By the same method as in reference example 5, on the basis of 1.42 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0.92 g of 4-(4-pyridyl)-3(2H, 4H)-1,2,4-triazolone get 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl]-4-(4-pyridyl)- 3(2H,4H)-1,2,4-triazole (0.66 g) as colorless prisms. T. pl. 96-97oC.

1H-NMR (CDCl3) : of 1.47 (3H, d, J = 7 Hz), 2,88 (1H, d, J = 4,6 Hz) and 3.15 (1H, d, J = 4,6 Hz), is 4.93 (1H, q, J = 7 Hz), 6,72-6,91 (2H, m), 7,26-7,40 (1H, m), a 7.62 (2H, dd, J = 4,8, and 1.6 Hz), 7,83 (1H, s), to 8.70 (2H, dd, J = 4,8, 1,6 Hz).

Calculated, %: C 59,30; H 4,10; N 16,27.

C17H14F2N4O2.

Found, %: C 59,23; H 4,12; N 16,36.

Reference example 27. By the same method as in reference example 5, on the basis of differenl)-2,3-epoxy-1-methylpropyl-4-(4-pyrimidinyl)- 3(2H, 4H)-1,2,4-triazole (199 mg) as a colourless oil.

1H-NMR (CDCl3) : of 1.47 (3H, d, J = 7,2 Hz), 2,90 (1H, d, J = 4,6 Hz), and 3.16 (1H, d, J = 4,6 Hz), the 4.90 (1H, q, J = 7,2 Hz), 6,72-of 6.90 (2H, m), 7,25-7,40 (1H, m), a 8.34 (1H, dd, J = 5,6, and 1.2 Hz), 8,46 (1H, s), 8,80 (1H, d, J = 5,6 Hz), 9,03 (1H, d, J = 1,2 Hz).

SIMS (m/z): 346 (M+H)+.

Reference example 28. By the same method as in the main example of 5 based on 1,36 g of (1S)-1-(2R)-2-(2,4-Differenl)-2-oxiranyl ethanol and of 0.91 g of 4-(2,2,2-triptorelin)-3(2H,4H)-1,2,4-triazolone get 2-(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl - 4-(2,2,2-triptorelin)-3(2H, 4H)-1,2,4-triazole (1.25 g) as a colourless oil.

IR cm-1(film): 1716, 1704, 1652, 1616, 1558, 1508.

1H-NMR (CDCl3) : USD 1.43 (3H, d, J = 7 Hz), 2,86 (1H, d, J = 4,6 Hz), 3,11 (1H, d, J = 4,6 Hz), 4,05 is 4.35 (2H, m), to 4.87 (1H, q, J = 7 Hz), 6,70-of 6.90 (2H, m), 7,20-of 7.25 (1H, m), 7,46 (1H, s).

Reference example 29. By the same method as in reference example 5, on the basis of 1.0 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and of 1.16 g of 4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -3(2H,4H)-1,2,4-triazolone get 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -3(2H, 4H)-1,2,4-triazole (1,34 g) as a colourless oil.

IR cm-1(film): 1716, 1705, 1616, 1558, 1516, 1257, 1108.

1H-NMR (CDCl3) : of 1.47 (3H, d, J = 7 Hz), 2,88 (1H, d, J = 4,8 Hz), and 3.16 (1H, d, J = 4,8 Hz), to 4.38 (2H, t, J = and 11.8 Hz), 4,94 (1H, q, J m, as in reference example 5, on the basis of 1.0 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.1 g of 4-(2-triptoreline)-3(2H, 4H)-1,2,4-triazolone get 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-(2-triptoreline)-3(2H, 4H)-1,2,4-triazole (0.4 g) as colorless powder.

1H-NMR (CDCl3) : to 1.48 (3H, d, J = 7,2 Hz), 2.91 in (1H, d, J = 4,4 Hz), 3,19 (1H, d, J = 4,4 Hz), equal to 4.97 (1H, q, J= 7,2 Hz), 6.75 in-6,90 (2H, m), 7.29 trend was 7.45 (3H, m), 7,56-to 7.84 (3H, m).

Reference example 31. By the same method as in reference example 5 based on 1,43 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0.94 g of 4-(4-isopropoxyphenyl)-3(2H, 4H)-1,2,4-triazolone get 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-(4-isopropoxyphenyl)-3(2H, 4H)-1,2,4-triazole (0.84 g) as a colourless oil.

1H-NMR (CDCl3) : of 1.34 (6H, d, J = 6,2 Hz) of 1.46 (3H, d, J = 7,2 Hz), 2,88 (1H, d, J = 4,6 Hz), 3,17 (1H, d, J = 4,6 Hz), 4,56 (1H, septet, J = 6,2 Hz), 4,96 (1H, q, J = 7,2 Hz), 6,72-6,91 (2H, m), 6,94 (2H, d, J = 8,4 Hz), 7,28-7,40 (1H, m), 7,34 (2H, d, J = 8,4 Hz), 7,58 (1H, s).

SIMS (m/z): 402 (M+H)+.

Reference example 32. By the same method as in reference example 5 according to 1.38 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and to 1.21 g of 4-(3-methylbutyl)-3(2H, 4H)-1,2,4-triazolone get 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] -4-(3-methylbutyl)- 3(2H,4H)-1,2,4-triazole (1,15 g) as a colourless oil.

SIMS (m/z): 338 (M+H)+.

Reference example 33. By the same method as in reference example 5, on the basis of 1.0 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and of 1.11 g of 4-[4-(1,1,2,2-tetrafluoroethoxy] -3(2H, 4H)-1,2,4-triazolone get 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazole (0,99 g) as a colourless oil.

IR cm-1(film): 1699, 1619, 1600, 1554, 1510, 1400.

1H-NMR (CDCl3) : of 1.47 (3H, d, J = 7,2 Hz), 2,89 (1H, d, J = 4,6 Hz), and 3.16 (1H, d, J = 4,6 Hz), of 4.95 (1H, q, J = 7,2 Hz), to 5.93 (1H, tt, J = 53 Hz, J = 2,8 Hz), 6,74-of 6.90 (2H, m), 7,25 was 7.45 (3H, m), 7,55 (2H, dt, J = 9 Hz, J = 2,2 Hz), to 7.67 (1H, s).

Reference example 34. By the same method as in reference example 5 according to 1.34 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol, and 1.15 g of 2-(4-chlorophenyl)-3(2H, 4H)-1,2,4-triazolone get 2-(4-chlorophenyl)-4-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 3(2H,4H)-1,2,4-triazole (519 mg) and 424 mg of (2R)-2-[(1R)-1-[1-(4-chlorophenyl)- 1H-1,2,4-triazole-5-yloxy]ethyl]-2-(2,4-differenl)oxirane.

2-(4-Chlorophenyl)-4-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl]-3(2H,4H)-1,2,4-triazole, colorless prisms. So pl. 172-173oC.

1H-NMR (CDCl3) : of 1.42 (3H, d, J = 7,4 Hz), 2,73 (1H, d, J = 4,4 Hz), 2,77 (1H, d, J = 4,4 Hz) to 5.00 (1H, q, J = 7,4 Hz), for 6.81-6,99 (2H, m), 7,32-of 7.48 (1H, m), 7,39 (2H, 3O2: 1,51 (3H, dd, J = 6,6, and 1.6 Hz), with 2.93 (1H, d, J = 4,6 Hz), 3,20 (1H, d, J = 4,6 Hz), and 5.30 (1H, q, J = 6,6 Hz), 6,78-of 6.96 (2H, m), 7,31-7,46 (1H, m), 7,40 (2H, d, J = 9 Hz), a 7.62 (2H, d, J = 9 Hz), to 7.64 (1H, s).

SIMS (m/z): 378 (M+H)+.

Reference example 35. The same method as in reference example 5 based on 1,53 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.50 g of 2-(4-trifloromethyl)-3(2H, 4H)-1,2,4-triazolone receive 4-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl]- 2-(4-trifloromethyl)-3(2H, 4H)-1,2,4-triazole (829 mg) and 778 mg (2R)-2-(2,4-differenl)-2-[(1R)-1-[1-(4-trifloromethyl)-1H - 1,2,4-triazole-5-yloxy]ethyl]oxirane.

4-[(R, 2S)-2-(2,4-Differenl)-2,3-epoxy-1-methylpropyl] - 2-(4-trifloromethyl)-3(2H,4 H)-1,2,4-triazole, colorless prisms. So pl. 116-117oC.

1H-NMR (CDCl3) : USD 1.43 (3H, d, J = 7,2 Hz), is 2.74 (1H, d, J = 4 Hz), 2,77 (1H, d, J = 4 Hz), free 5.01 (1H, q, J = 7,2 Hz), 6,80-7,00 (2H, m), 7,28 (2H, d, J = 9,2 Hz), 7,33-7,50 (1H, m), to 7.61 (1H, s), with 8.05 (2H, d, J = 9,2 Hz).

Calculated, %: C 53,40; H 3,30; N 9,83.

C19H14F5N3O3.

Found, %: C 53,09; H 3,23; N 9,83.

(2R)-2-(2,4-Differenl)-2-[(1R)-1-[1-(4-trifloromethyl)-1H - 1,2,4-triazole-5-yloxy]ethyl]oxirane, colorless oil.

1H-NMR (CDCl3) : is 1.51 (3H, d, J = 6,6 Hz), to 2.94 (1H, d, J = 4,8 Hz), 3,20 (1H, d, J = 4,8 Hz), 5,31 (1H, q, J = 6,6 Hz), 6,78-6,98 (2H, m), 7,29 (2H, d, J = 9 Hz), 7,35 is 7.50 (1H, m), the 7.65 (1H, s), 7, the extent of 5 based on 1.54 g of (1S)-1-[(2R)-(2,4-differenl)-2-oxiranyl]ethanol and 1.52 g of 1-(4-trifloromethyl)-5(1H, 4H)-tetrazole gain of 1.76 g of 1-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl]- 4-(4-trifloromethyl)-5(1H, 4H)-tetrazole in the form of a colorless oil.

1H-NMR (CDCl3) : to 1.60 (3H, d, J = 7,4 Hz), with 2.93 (1H, d, J = 4,4 Hz), 3,17 (1H, d, J = 4,4 Hz), is 4.93 (1H, q, J = 7,4 Hz) 6,75-of 6.96 (2H, m), 7.24 to the 7.43 (1H, m), 7,35 (2H, d, J = 9,2 Hz), 8,00 (2H, d, J = 9,2 Hz).

IRneamaxtcm-1: 2980, 1732, 1620, 1601, 1514, 1427.

SIMS (m/z): 429 (M+H)+.

Reference example 37. By the same method as in reference example 5, on the basis of 1.39 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.63 g of 1-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -5(1H, 4H)-tetrazole obtain 1.27 g of 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-5(1H,4H)-tetrazole in the form of a colorless oil.

1H-MMR (CDCl3) : to 1.60 (3H, d, J = 7,2 Hz), with 2.93 (1H, d, J = 4,4 Hz), 3,17 (1H, d, J = 4,4 Hz), and 4.40 (2H, t, J = 11.8 in Hz), is 4.93 (1H, q, J = 7,2 Hz), between 6.08 (1H, tt, J = 53,2, and 4.6 Hz), 6.73 x-6,94 (2H, m), 7,05 (2H, d, J = 9 Hz), of 7.23-7,41 (1H, m), 7,86 (2H, d, J = 9 Hz).

IRneamaxtcm-1: 3000, 1745, 1622, 1601, 1522, 1431.

SIMS (m/z): 475 (M+H)+.

Reference example 38. By the same method as in reference example 5 according to 1.38 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.09 g of 1-(4-chlorophenyl)-5(1H, 4H)-tetrazole obtain 1.27 g of 1-(4-chlorophenyl)-4-[(1R, 2S)-2-(2,4-differenl)-2,3-a,2 Hz), of 2.92 (1H,d, J = 4,4 Hz), and 3.16 (1H, d, J = 4,4 Hz), to 4.92 (1H, q, J = 7,2 Hz), 6.75 in-of 6.96 (2H, m), 7,25-7,41 (1H, m), 7,45 (2H, d, J = 9 Hz), of 7.90 (2H, d, J = 9 Hz).

IRneamaxtcm-1: 3018, 1732, 1620, 1506, 1425.

SIMS (m/z): 379 (M+H)+.

Reference example 39. By the same method as in reference example 5, on the basis of 1.01 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol, and 1.15 g of 1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl] -2(1H, 3H)-imidazole obtain 0.36 g of 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl] -2(1H,3H)-imidazolone in the form of colorless needles. So pl. 117-118oC.

1H-NMR (CDCl3) : of 1.37 (3H, d, J = 7,2 Hz), 2,71 (1H, d, J = 5 Hz), of 2.81 (1H, d, J = 5 Hz), to 5.08 (1H, q, 7,2 Hz), to 5.93 (1H, tt, J = 53, 2,8 Hz), 6,46 (1H, d, J = 3 Hz), to 6.57 (1H, d, J=3 Hz), 6,80-to 6.95 (2H, m), 7,28 (2H, d, J = 9Hz), was 7.36-of 7.48 (1H, m), to 7.67 (2H, d, J = 9 Hz).

Reference example 40. By the same method as in reference example 5 according to 0.80 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0.78 g of 1-(4-chlorophenyl)-2(1H, 3H)-imidazolone obtain 0.18 g of 1-(4-chlorophenyl)-3-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 2(1H, 3H)-imidazolone in the form of a colorless viscous oil.

1H-NMR (CDCl3) : of 1.36 (3H, d, J = 7 Hz), 2,70 (1H, d, J = 5 Hz), 2,80 (1H, d, J = 5 Hz), 5,07 (1H, q, J = 7 Hz), of 6.45 (1H, d, J = 3,2 Hz), 6,55 (1H, d, J = 3,2 Hz), 6,79-6,94 (2H, m), 7,34-7,46 (1H, m), 7,38 (2H, d, J = 9 Hz), to 7.59 (2H, d, J = 9 Hz).

Reference example 41. The same method B1,2,4-triazoline get to 0.23 g of 4-(4-chlorophenyl)-2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 3(2H,4H)-1,2,4-triazolone in the form of a colorless viscous oil.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7 Hz), 2,88 (1H, d, J = 5 Hz) and 3.15 (1H, d, J = 5 Hz), 4,94 (1H, q, J = 7 Hz), 6,76-to 6.88 (2H, m), 7,26-7,50 (1H, m), 7,46 (4H, s), 7,66 (1H, s).

Reference example 42. By the same method as in reference example 5 based on 0,83 g of (1S)-1-1(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 1.56 g of 1-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl] -2-(1H, 3H)-imidazolone gain of 0.30 g of 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 3-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl] -2(1H, 3H)-imidazolone in the form of a colorless viscous oil.

1H-NMR (CDCl3) : of 1.36 (3H, d, J = 7,2 Hz), 2,70 (1H, d, J = 4,8 Hz), 2,80 (1H, d, J = 4,8 Hz), 4,48 (2H, t, J = 13 Hz), 5,07 (1H, q, J = 7,2 Hz), 6,09 (1H, tt, J = 52, and 5.6 Hz), to 6.43 (1H, d, J = 3,2 Hz), 6,51 (1H, d, J = 3,2 Hz), 6,79-of 6.96 (2H, m), 7,00 (2H, d, J = 9 Hz), 7,34-7,47 (1H, m), EUR 7.57 (2H, d, J = 9 Hz).

Reference example 43. By the same method as in reference example 5 according to 0.68 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and 0.70 g of 1-[4-(2,2,2-triptoreline)phenyl] -2(1H,3H)-imidazolone gain of 0.30 g of 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 3-[4-(2,2,2-triptoreline)phenyl]-2(1H,3H)-imidazolone in the form of colorless prisms.

1H-NMR (CDCl3) : of 1.36 (3H, d, J = 7,2 Hz), 2,71 (1H, d, J = 4,8 Hz), of 2.81 (1H, d, J = 4,8 Hz), 4,37 (2H, q, J = 8 Hz), *) of 6.52 (1H, d, J = 3,2 Hz), to 6.43 (1H, q, J = 3,2 Hz), 6,80-as in reference example 5, on the basis of 1.0 g of (1S)-1-[(2R)-2-(2,4-Differenl)-2-oxiranyl]ethanol and of 1.23 g of 1-[4-(2,2,3,3,3-pentafluoropropane)phenyl] -2(1H,3H)-imidazolone gain of 0.43 g of 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl]- 3-[4-(2,2,3,3,3-pentafluoropropane)phenyl]-2(1H,3H)-imidazolone in the form of colorless plates.

1H-NMR (CDCl3) : of 1.36 (3H, d, J = 7,2 Hz), 2,71 (1H, d, J = 4,8 Hz), of 2.81 (1H, d, J = 4,8 Hz), of 4.44 (2H, t, J = 12 Hz), to 5.08 (1H, q, J = 7,2 Hz), 6,44 (1H, d, J = 3,2 Hz), of 6.52 (1H, d, J = 3,2 Hz), 6,78-to 6.95 (2H, m), 7,00 (2H, d, J = 9,2 Hz), 7,35-of 7.48 (1H, m), EUR 7.57 (2H, d, J = 9,2 Hz).

Reference example 45. By the same method as in reference example 5, on the basis of 0.73 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0.73 g of 4-[4-(2,2,2-triptoreline)phenyl] -3(2H, 4H)-1,2,4-triazolone obtain 0.74 g of 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-[4-(2,2,2-triptoreline)phenyl]-3(2H,4H)-1,2,4-triazolone in the form of a colorless oil.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7 Hz), 2,88 (1H, d, J = 4,6 Hz) and 3.15 (1H, d, J = 4,6 Hz), to 4.38 (2H, q, J = 8 Hz), 4,94 (1H, q, J = 7 Hz), 6,74-of 6.90 (2H, m), 7,02 (2H, d, J = 9,2 Hz), of 7.36-7,50 (1H, m), 7,44 (2H, d, J = 9,2 Hz), a 7.62 (1H, s).

Reference example 46. By the same method as in reference example 5 according to 0.94 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and of 1.16 g of 4-[4-(2,2,3,3,3-pentafluoropropane)phenyl] -3(2H, 4H)-1,2,4-triazolone gain of 0.68 g of 2-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 4-[4-(2,2,3,3,3-pentafluoropropane)phenyl] -3(2H, 4H)-1,2,4-triazolone in the form of a colorless oil.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7 Hz), 2,88 (1H, d, J = 4,6 Hz) and 3.15 (1H, d, J = 4,6 Hz), of 4.44 is Ilony example 47. By the same method as in reference example 5 according to 0.70 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and of 1.17 g of 4-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl]-3(2H,4H)- 1,2,4-triazolone obtain 0.18 g of 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl]-4-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl] -3(2H, 4H)- 1,2,4-triazolone in the form of a colorless viscous oil.

1H-NMR (CDCl3) : of 1.47 (3H, d, J = 7 Hz), 2,88 (1H, d, J = 5 Hz), and 3.16 (1H, d, J = 5 Hz), of 4.49 (2H, t, J = 13 Hz), of 4.95 (1H, q, J = 7 Hz), 6,10 (1H, tt, J = 52, of 5.4 Hz), 6.75 in-6,90 (2H, m),? 7.04 baby mortality (2H, d, J = 9,0 Hz), 7,25-7,42 (1H, m), 7,45 (2H, d, J = 9,0 Hz), a 7.62 (1H, s).

Reference example 48. By the same method as in reference example 5 based on 0,971 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.0 g of 2-[4-(2,2,2-triptoreline)phenyl] -3(2H, 4H)-1,2,4-triazolone get 0,825 g of 4-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 2-[4-(2,2,2-triptoreline)phenyl] -3-(2H,4H)-1,2,4-triazolone in the form of colorless prisms. T. pl. 118-119oC.

1H-NMR (CDCl3) : of 1.42 (3H, d, J = 7,2 Hz), 2,73 (1H,d, J = 4,2 Hz), 2,77 (1H, d, J = 4,2 Hz), 4,37 (2H, q, J = 8,2 Hz), 5,00 (1H, q, J = 7,2 Hz), for 6.81-7,02 (2H, m), 7,00 (2H, d, J = 9,2 Hz), 7,31-7,50 (1H, m), to 7.59 (1H, s), to 7.93 (2H, d, J = 9,2 Hz).

Reference example 49. By the same method as in reference example 5 according to 0.98 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.04 g of 2-[4-(2,2,3,3,3-pentafluoropropane)phenyl] -3(2H, 4H)- 1,2,4-triazolone get 0,882 g of 4-[(1R, 2S)-2-(2 who's prisms. So pl. 128-129oC.

1H-NMR (CDCl3) : USD 1.43 (3H, d, J = 7,2 Hz), 2,73 (1H, d, J = 4,2 Hz), 2,77 (1H, d, J = 4,2 Hz), of 4.44 (2H, t, J = and 12.2 Hz), free 5.01 (1H, q, J = 7,2 Hz), 6,80-7,01 (2H, m), 7,01 (2H, d, J = 9,2 Hz), 7,32-7,49 (1H, m), to 7.59 (1H, s), 7,94 (2H, d, J = 9,2 Hz).

Reference example 50. By the same method as in reference example 5 based on 345 mg (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 410 mg of 2-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl] -3-(2H, 4H)- 1,2,4-triazolone receive 371 mg of 4-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl]-2-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl] -3(2H, 4H)- 1,2,4-triazolone in the form of colorless prisms.

1H-NMR (CDCl3) : of 1.42 (3H, d, J = 7 Hz), 2,73 (1H, d, J = 4,2 Hz), 2,77 (1H, d, J = 4,2 Hz), of 4.49 (2H, t, J = 13 Hz), 5,00 (1H, d, J = 7 Hz), 6,12 (1H, tt, J = 52, of 5.4 Hz), 6,80-7,01 (2H, m), 7,01 (2H, d, J = 9,2 Hz), 7,30-7,50 (1H, m), to 7.59 (1H, s), 7,94 (2H, d, J = 9,2 Hz).

Reference example 51. By the same method as in reference example 5 based on 0,975 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl] ethanol and 1.13 g of 2-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -3(2H, 4H)-1,2,4-triazolone get 0,847 g of 4-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 2-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -3(2H, 4H)-triazolone in the form of colorless prisms. So pl. 116-117oC.

1H-NMR (CDCl3) : of 1.42 (3H, d, J = 7,2 Hz), 2,73 (1H,d, J = 4,2 Hz), 2,77 (1H, d, J = 4,2 Hz), 4,37 (2H, tt, J = 11.8 in, and 1.6 Hz), 5,00 (1H, q, J = 7,2 Hz), between 6.08 (1H, tt, J = 53, 5Hz), 6,79? 7.04 baby mortality (2H, m), of 6.99 (2H, d, J = a 9.4 Hz), 7,32-7,4 C of 1.15 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 1.27 g of 2-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazolone obtain 1.20 g of 4-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] - 2-[4-1,1,2,2-tetrafluoroethoxy)phenyl] -3(2H, 4H)-1,2,4-triazolone in the form of colorless needles. So pl. 105-106oC.

1H-NMR (CDCl3) : USD 1.43 (3H, d, J = 7,2 Hz), is 2.74 (1H, d, J = 4,4 Hz), 2,77 (1H, d, J = 4,4 Hz), free 5.01 (1H, q, J = 7,2 Hz), of 5.92 (1H, tt, J = 53, 2,8 Hz), for 6.81-7,01 (2H, m), 7,28 (2H, d, J = 9,2 Hz), 7,30-7,49 (1H, m), to 7.61 (1H, s), of 8.04 (2H, d, J = 9,2 Hz).

Reference example 53. 2,4-Diptiranjan (25 g) 25.2 g of pyridine are dissolved in 200 ml of dichloromethane, to which is added dropwise under ice cooling to 33.3 g of phenyl chloroformate. After stirring under ice cooling for 30 min the reaction solution was washed with water and then dried by evaporation of solvent to obtain a mixture of phenyl 2,4-divergencelimit and pyridine. To the mixture of 30.7 g of 2-(diethoxy)ethylamine and the mixture is stirred at room temperature. The crystals are separated by filtration and washed with petroleum ether to obtain of 37.8 g of N-(2,2-diatexite)-N'-(2,4-differenl)urea as colorless crystals.

This urea (37,5 g) dissolved in a mixture of 560 ml of methanol and 280 ml of water, then add to 0.48 M hydrochloric acid and the resulting mixture is stirred for three days at room temperature. The reaction solution is concentrated under reduced pressure. The separated crystals are washed mixture is SUP>oC.

Calculated, %: C 55,11; H Is 3.08; N Of 14.28.

C9H6F2N2O.

Found, %: C 55,14; H 3,29; N 14,18.

Reference examples 54-63. Derivatives imidazolone presented in table. 1 and 2, were obtained in the same manner as in reference example 53.

Reference example 64

To diethylacetal of aminoacetaldehyde (7.8 ml, 53.6 mmol) was added dropwise 10 g (with 53.4 mmol) 4-triftormetilfullerenov at 0oC for 5 minutes the Reaction solution is stirred for 1 h at room temperature. The crystals obtained are collected by filtration and washed with hexane to obtain 16.2 g of 1-(2,2-diatexite)-3-(4 - triptoreline)urea (95%) as a colorless powder.

1-(2,2-Diatexite)-3-(4-triptoreline)urea (9,2 g, 28.7 mmol) dissolved in a mixture of 113 ml of methanol and 57 ml of water. To the reaction solution was added to 67.5 ml of 0.48 G. hydrochloric acid and the mixture is stirred for 48 h at room temperature. To the reaction solution add sodium hydroxide to reach pH 7, followed by concentration under reduced pressure. The residue is extracted with ethyl acetate (100 ml x 4). The extracts are combined, washed with water and saturated aqueous sodium chloride, dried isopropylacrylamide ether with getting to 4.87 g of 1-(4-triptoreline)-2(1H, 3H)-imidazolone (74%) as colorless prisms. So pl. 170-171oC.

Reference example 65.

4-Cryptomaterial (20 g) and 9.8 g of pyridine are dissolved in 150 ml of ethyl acetate and cooled with ice added 19.5 g of phenyl chloroformate. After stirring for 15 min with ice cooling, the reaction solution is washed with water, dried and the solvent is distilled off under reduced pressure. The separated crystals are washed with hexane to obtain to 34.1 g of phenyl 4-triphtalocyaninine in the form of colorless crystals.

This carbamate (15 g) and 6 ml of hydrazine hydrate is added is stirred in 50 ml of ethanol for 2 hours, the Reaction solution is concentrated under reduced pressure and the residue was washed with cold ethyl acetate to obtain 11.7 g of 4-(4-trifloromethyl) semicarbazide in the form of colorless crystals.

After stirring 7.0 g of this semicarbazide and 15.5 g of formamidine in 150 ml of dimethylformamide at room temperature for 30 min, added to 8.9 g of acetic acid, and the mixture is heated at 80oC for 6 hours the Solvent is removed by distillation under reduced pressure. To the residue is added ethyl acetate and a saturated aqueous solution of sodium chloride. The organic layer is dried and konzentrieren in the form of colorless crystals (3,44 g). So pl. 193-195oC.

1H-NMR (CDCl3) : 7,37 (2H, d, J = 9 Hz), 7,63 (2H, dt, J = 9 Hz, J = 2 Hz), 7,73 (1H, d, J = 1,4 Hz), 10,23 (1H,br).

Reference examples 66-84. In the same way as in reference example 65 were obtained derivatives triazolone presented in table. 3-5.

Reference example 85. K the solution of 3-methylbutylamine (20 g, 229 mol) in 840 ml of dichloromethane at 0oC add a 35.6 ml of triethylamine (255 mol) and 28.8 ml phenylcarbamate (230 mmol). The mixture is stirred for 3 h at room temperature. After removal of the solvent under reduced pressure, to the residue was added 200 ml of ethyl acetate and 200 ml of water. The organic layers separated and the aqueous layer extracted with ethyl acetate (100 ml x 3). The organic layers are combined, washed with water and saturated sodium chloride solution and dried over magnesium sulfate. The solvent is evaporated, the crystals are separated by filtration and washed with petroleum ether to obtain 39.5 g phenyl 3-methylbutylamine (83%) as colorless crystals.

To a solution of 3-methylbutylamine (18.5 g, 8.9 mmol) in 210 ml of dioxane add 22 ml of hydrazine hydrate is added and the mixture is refluxed for 3 hours After cooling, the solvent is evaporated under reduced pressure. The residue is dissolved in 200 is giving 1 h at room temperature. The precipitate is collected by filtration, washed with ethyl acetate (50 ml x 2) and dried to obtain 14.8 g of 4-(3-methylbutyl)the formation of hydrochloride (91%) as a white powder.

A mixture of 13.0 g of 4-(3-methylbutyl)semicarbazide hydrochloride (71,6 mmol) and 60 ml of ethylformate stirred for 2 h at 110oC. After cooling, the mixture is subjected to chromatography on a column of silica gel (eluent - ethyl acetate: hexane = 1: 2 to 2:1 ethyl acetate ethyl acetate:methanol = 10:1). The desired fractions are concentrated. Thus obtained crystals are recrystallized from ethyl acetate - petroleum ether to obtain 7.0 g of 4-(3-methylbutyl)-3(2H,4H)-1,2,4-triazolone (63%) as colourless needles. So pl. 78-79oC.

1H-NMR (CDCl3) _ as 0.96 (6H, d, J = 6,4 Hz), 1,53-1,72 (3H, m), 3,66 (2H, t, J = 7,4 Hz), 7,39 (1H, s).

Calculated, %: C 54,17; H 8,44; N 27,07.

C7H13N3O.

Found, %: C 54,14; H Of 8.47; N 27,14.

Reference example 86. To a mixture of 5.0 g of 4-(trifluoromethyl)phenylhydrazine (28.4 mmol), 31 ml of water and 3.1 ml of concentrated hydrochloric acid added 2.9 g of hydrate piotrowo acid (of 31.4 mmol) and the mixture stirred for 1 h at room temperature. Thus obtained precipitate was separated and collected by filtration, washed with water and dried NGOs powder.

4-(trifluoromethyl)phenylhydrazones acid (6,26 g, 27 mmol) is suspended in 176 ml of toluene and added to 4.0 ml of triethylamine (28.7 mmol) and 6.1 ml diphenylphosphinite (28.3 mmol) and the resulting mixture was stirred for 1 h at 120oC. After cooling, the reaction solution is extracted with 200 ml of an aqueous solution of potassium hydroxide (10%). The aqueous extract is acidified with concentrated hydrochloric acid to pH 1, the thus obtained crystals are separated, washed with water and hexane and dried over pjatiokisi phosphorus obtaining 4,48 g of 2-(4-triptoreline)-3(2H,4H)-1,2,4-triazolone in the form of colorless powder. So pl. 221oC.

Reference examples 87-94.

In the same way as in reference example 86 were obtained derivatives triazolone presented in table. 6.

Reference example 95.

In the same way as in reference example 64 was obtained 1-(4-forfinal)-2(1H,3H)-imidazolone. So pl. 166-167oC.

Reference example 96. To 4-triptoreline isocyanate (2,89 ml, at 20.2 mmol) is added are 5.36 ml azidotimedine (and 39.9 mmol) and the mixture was stirred at 110oC within 24 hours After cooling, the mixture is subjected to chromatography on a column of silica gel (eluent - ethyl acetate:hexane = 1:1 to 2:1 ethyl acetate - hexane obtaining of 3.64 g of 1-(4-triptoreline)-5(1H, 4H)-tetrazole (78%) as colorless needles. So pl. 191-192oC.

Reference examples 97-104. In the same way as in reference example 96 was obtained derivatives triazolone presented in table. 7.

Reference example 105. 1-[4-(1,1,2,2-Tetrafluoroethoxy)phenyl]the formation of (6.0 g) and 10.6 g of hydrochloridetramadol dissolved in 100 ml of dimethylformamide. The solution is stirred for 1 h at room temperature. After adding 6.6 g of acetic acid, the reaction solution is heated at 80oC for 7 h and concentrated under reduced pressure. The residue is dissolved in a mixture of 200 ml of ethyl acetate and 40 ml of water. The separated organic layer is washed with water and saturated aqueous sodium chloride, dried and the solvent is distilled off. The residue is recrystallized from ethyl acetate to obtain 3.6 g of 5-methyl-4-[4- (1,1,2,2-tetrafluoroethoxy)phenyl] -3(2H,4H)-1,2,4-triazolone in the form of colorless needles. T. pl. 204-205oC.

1H-NMR (DMSO-d6) _: of 2.08 (3H, s), at 6.84 (1H, tt, J = 51,8 Hz, J = 3,2 Hz), the 7.43 (2H, d, J = 8,8 Hz), 7,55 (2H, d, J = 8,8 Hz), 11,57 (1H, s).

Reference example 106. By the same method as in reference example 105, receive 5-methyl-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -3(2H, 4H)- 1,2,4-triazolone. So pl. 206-207oC.< 50 ml water and 25 ml of ethanol, to which are added dropwise 1,69 g 80% aqueous solution of acetaldehyde, the resulting mixture was stirred at room temperature for 30 minutes After adding 50 ml of water the reaction mixture is extracted with ethyl acetate. The organic layer is washed with water and saturated sodium chloride solution, dried and the solvent is distilled off to obtain acetaldehyde 4-chlorophenylhydrazone in the form of butter.

The hydrazone is dissolved in 15 ml of acetic acid, add 1,82 g aqueous suspension of sodium cyanate, the mixture is stirred for 1 h at room temperature. The precipitated crystals are collected by filtration and washed with water to obtain 4.8 g of 2-(4-chlorophenyl)-5-methyl-1,2,4-triazolin-3-one as a red-brown powder.

A mixture of 1.0 g of 2-(4-chlorophenyl)-5-methyl-1,2,4-triazolin-3-one, a 50% aqueous solution of 2.28 g of sodium hydroxide and 0.11 g of tributylammonium in 25 ml of toluene is stirred for 4 h at 60oC. After cooling, the reaction mixture is diluted with 25 ml of water. The aqueous layer was separated by acidification with concentrated HCl. The precipitated crystals are collected by filtration and recrystallized from ethyl acetate-diisopropyl ether to obtain 0.56 g of 2-(4-chlorophenyl)-5-methyl-3(2H-4H)-1,2,4-triazolone in the form of colorless needles. So pl. 218-219oC.

oC.

Reference example 109. By the same method as in reference example 5 according to 0.44 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0,48 g 1-[4-[4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -1-piperazinil]phenyl]- 2(1H,3H)-imidazolone obtain 0.11 g of 1-[(1R,2S)-2-(2,4-differenl)- 2,3-epoxy-1-methylpropyl] -3-[4-[4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] - 1-piperazinil] phenyl]-2(1H,3H)-imidazolone in the form of colorless powder,

1H-NMR (CDCl3) : of 1.36 (3H, d, J = 7,2 Hz), 2,70 (1H, d, J = 4,8 Hz), of 2.81 (1H, d, J = 4,8 Hz), 3,22 is 3.40 (8H, m), or 4.31 (2H, t, J = 12 Hz), 5,07 (1H, q, J = 7,2 Hz), 6,07 (1H, tt, J = 53, 5,2 Hz), 6,40 (1H, d, J = 3,2 Hz), of 6.50 (1H, d, J = 3,2 Hz), 6,70-7,03 (8H, m), 7,22-7,51 (3H, m).

Reference example 110. By the same method as in reference example 5, on the basis of 0.31 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0.50 g 4-[4-[4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -1-piperazinil]phenyl]- 3(2H,4H)-1,2,4-triazolo obtain 0.15 g of 2-[(1R,2S)-2-(2,4-differenl)- 2,3-epoxy-1-methylpropyl] -4-[4-[4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] - 1-piperazinil]phenyl]-3(2H,4H)-triazolone in the form of colorless powder.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7,0 Hz), 2,88 (1H, d, J = 5 Hz), and 3.16 (1H, d, J = 5 Hz), 3,22-3,39 (8H, m), or 4.31 (2H, t, J = and 12.2 Hz), 4,96 (1H, q, J = 7,0 Hz), 6,07 (1H, tt, J = 53, 5,0 Hz), 6.75 in-7,03 (8H, m), 7.23 percent-7,40 (3H, m)afterfeel)-2-oxiranyl]ethanol and 0.31 g of 1-[4-(2,2,2-triptoreline)phenyl]-5(1H,4H)-1,2,4-tetrazole obtain a mixture (3: 2, 0,22 g) 1-[(1R,2S)-2- (2,4-differenl)-2, 3-epoxy-1-methylpropyl]-4-[4-(2,2,2-triptoreline)phenyl] -5(1H, 4H)- 1,2,4-tetrazole and (2R)-2-(2,4-differenl)-2-[(1R)-1-[1-[4-(2,2,2- triptoreline)phenyl] -1H-tetrazol-5-yloxy]ethyl]oxirane in the form of a colorless oil.

1H-NMR (CDCl3) : 1.55V (d, J = 7 Hz), 1,60 (d, J = 8Hz), with 2.93 (d, J = 4,5 Hz), 2,96 (d, J = 4,8 Hz), 3,17 (d, J = 4,5 Hz), 3,20 (d, J = 4,8 Hz), and 4.40 (q, J = 8 Hz), of 4.44 (q, J = 8 Hz), is 4.93 (q, J = 8 Hz), 5,31 (q, J = 7 Hz), 6,77-6,95 (m), 7,06 (d, J = 9,2 Hz), to 7.09 (d, J = 9,2 Hz), 7,27 was 7.45 (m), to 7.61 (d, J = 9,2 Hz), 7,86 (d, J = 9,2 Hz).

Reference example 112. By the same method as in reference example 5 based on 1,049 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl] ethanol and of 1.17 g of 1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl] -5(1H, 4H)-tetrazole obtain 1.28 g of 1-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl]- 4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-5(1H,4H)tetrazole in the form of a colorless oil.

1H-NMR (CDCl3) : to 1.61 (3H, d, J = 7 Hz), with 2.93 (1H, d, J = 4,4 Hz), 3,17 (1H, d, J = 4,4 Hz), is 4.93 (1H, q, J = 7 Hz), 5,94 (1H, tt, J = 52,8, and 2.6 Hz), 6.75 in-6,94 (2H, m), 7.24 to 7,40 (1H, m), 7,34 (2H, d, J = 9 Hz), 7,98 (2H, d, J = 9 Hz).

IRneamaxtcm-1: 3060, 1734, 1618, 1599, 1510, 1427.

Reference example 113. By the same method as in reference example 5 based on 0,962 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl] ethanol and 1.19 g of 1-[4-(2,2,3,3,3-pentafluoropropane)phenyl] -5(1H,4H)-tetrazole gain of 1.31 g of 1-[(1R,2S)-2-(2,4-SS="ptx2">

1H-NMR (CDCl3) : to 1.60 (3H, d, J = 7 Hz), 2,92 (1H, d, J = 4,4 Hz), and 3.16 (1H, d, J = 4,4 Hz), 4,46 (2H, dt, J = 12, 1 Hz), to 4.92 (1H, q, J = 7 Hz), 6.75 in-6,93 (2H, m), 7,05 (2H, d, J = 9,2 Hz), 7,20-7,38 (1H, m), 7,86 (2H, d, J = 7 Hz).

IRneamaxtcm-1: 3060, 1732, 1618, 1601, 1558, 1516, 1427.

Reference example 114. By the same method as in reference example 5 based on 0,988 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl] ethanol and 1.55 g of 1-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl] -5(1H, 4H)tetrazole received a mixture (7: 3, 1,72 g) 1-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl] -4-[4-(2,2,3,3,-4,4,5,5-octadecenoic)phenyl]-5(1H,4H)- tetrazocine and (2R)-2-(2,4-differenl)-2-[(1R)-1-[1-[4-(2,2,3,3,4,4,5,5- octadecenoic)phenyl]-1H-tetraol-5-yloxy]ethyl]oxirane in the form of a colorless oil.

1H-NMR (CDCl3) : 1.55V (dd, J = 6,6 and 1.5 Hz), 1,60 (d, J = 7,2 Hz), with 2.93 (d, J = 4,5 Hz), 2,95 (d, J = 4,8 Hz), 3,17 (d, J = 4,5 Hz), 3,20 (d, J = 4,8 Hz), 4,51 (t, J = 12,9 Hz), 4,55 (t, J = 12,8 Hz), is 4.93 (q, J = 7,2 Hz), 5,31 (q, J = 7,2 Hz), 6,10 (tt, J = 52, 5,5 Hz), 6,11 (tt, J = 52, at 5.3 Hz), 6,74-6,94 (m), 7,06 (d, J = 9 Hz), to 7.09 (d, J = 9 Hz), 7,28 was 7.45 (m), to 7.61 (d, J = 9 Hz), 7,86 (d, J = 9 Hz).

Reference example 115. By the same method as in reference example 5, on the basis of 0.50 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0.61 g of 5-methyl-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -3(2H,4H)-1,2,4 - triazolone obtain 0.45 g of 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl]-5-methyl-4-[4-(2,2,3,3-tetrafluoropropoxy)Fenin, d, J = 4,8 Hz), 3,17 (1H, d, J = 4,8 Hz), to 4.38 (2H, t, J = and 11.8 Hz), 4,94 (1H, q, J = 7,2 Hz), the 6.06 (1H, tt, J = 53 Hz, J = 4,7 Hz), 6,74-of 6.90 (2H, m), 7,02 (2H, dt, J = 9,2 Hz, J = 2,6 Hz), 7,18 (2H, dt, J = 9,2 Hz, J = 2,6 Hz), 7,28-the 7.43 (1H, m).

Reference example 116. By the same method as in reference example 5, on the basis of 0.50 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and of 0.58 g of 5-methyl-4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl] -3(2H, 4H)- 1,2,4-triazolone receive and 0.46 g of 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl]-5-methyl-4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)- 1,2,4-triazolone in the form of a colorless oil.

1H-NMR (CDCl3) : of 1.45 (3H, d, J = 7 Hz), of 2.15 (3H, s), 2,87 (1H, d, J = 4,6 Hz), 3,18 (1H, d, J = 4,6 Hz), 4,94 (1H, q, J = 7 Hz), 5,94 (1H, tt, J = 2,6 Hz), 6,74-of 6.90 (2H, m), 7,25-7,42 (5H, m).

Reference example 117. By the same method as in reference example 5 according to 0.70 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0.62 g of 2-(4-chlorophenyl)-5-methyl-3(2H, 4H)-1,2,4-triazolone obtain 0.28 g of 2-(4-chlorophenyl)-4-[(1R, 2S)-2-(2,4-differenl)-2,3-epoxy - 1-methylpropyl]-5-methyl-3(2H,4 H)-1,2,4-triazolone in the form of a colorless oil.

1H-NMR (CDCl3) : of 1.55 (3H, d, J = 7,2 Hz), 2,24 (3H, s), to 2.94 (1H, d, J = 4,2 Hz), and 3.16 (1H, d, J = 4,2 Hz), to 4.81 (1H, q, J = 7,2 Hz), 6,78-6,93 (2H, m), 7,30-7,46 (1H, m), of 7.36 (2H, d, J = 9 Hz), of 7.90 (2H, d, J = 9Hz).

Reference example 118. By the same method as in reference example 5, on the basis of 0.50 g of (1S)-1-[(2R)-2-(2,4-differenl)-2-oxiranyl]ethanol and 0.52 g of 5-m] - 5-methyl-2-(4-trifloromethyl)-3(2H, 4H)-1,2,4-triazolone in the form of a colorless viscous oil.

1H-NMR (CDCl3) : of 1.55 (3H, d, J = 7 Hz), 2,24 (3H, s), of 2.92 (1H, d, J = 4 Hz), and 3.16 (1H, d, J = 4 Hz), to 4.81 (1H, q, J = 7 Hz), 6,78-6,91 (2H, m), 7,25 (2H, d, J = 9 Hz), 7,33-7,44 (1H, m), of 7.97 (2H, d, J =9 Hz).

Working example 1. A mixture of 300 mg of (2R,3S)-2-(2,4-differenl)-3-methyl - 2-[(1H-1,2,4-triazole-1-yl)methyl] oxirane and 2.77 g of 1-phenyl-2 - trimethylsilylimidazole stirred in argon atmosphere at 180oC for 4 h, After cooling, to the reaction solution was added 50 ml of chloroform and 50 ml of water. The separated aqueous layer further extracted with 10 ml of chloroform. The organic extracts are combined, washed with water and saturated aqueous sodium chloride and dried over magnesium sulfate. The solvent is evaporated under reduced pressure. The residue is purified using chromatography on silica gel (eluent - ethyl acetate: hexane = 1:2 to 1:1) to obtain 16 g of 1-[(1R,2S)-2-(2,4-differenl)-1-methyl-3-(1H-1,2,4-triazole-1-yl)- 2-trimethylsilyl-oksipropil]-3 - phenyl-2(1H,3H)- imidazolone.

1H-NMR (CDCl3) : 0,28 (9H, s), of 1.09 (3H, d, J = 7 Hz), 4,35 (1H, d, J = 15 Hz), is 5.06 (1H, q, J = 7 Hz), 5,28 (1H, dd, J = 15, 2 Hz), 6,62 (1H, d, J = 3,2 Hz), of 6.71 (1H, d, J = 3,2 Hz), 6.75 in-6,91 (2H, m), 7,25-the 7.65 (6H, m), to 7.67 (1H, s), 7,89 (1H, s).

To a solution of 118 mg of the compounds in 6 ml of tetrahydrofuran debony the solution is concentrated under reduced pressure. The residue is purified using chromatography on silica gel (eluent - ethyl acetate:hexane = 1:1 to 21:1) to give 83 g of [1-[(1R,2S)-2-(2,4-differenl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazole - 1-yl)propyl] -3-phenyl-2(1H,3H)-imidazolone (Compound 1) as a yellow powder.

1H-NMR (CDCl3) ; to 1.21 (3H, d, J = 7 Hz), 4,20 (1H, d, J = 14,4 Hz), of 4.95 (1H, q, J = 7 Hz), 5,11 (1H, d, J = 14,4 Hz), 5,64 (1H, s), of 6.66 (1H, s, J = 3,2 Hz), was 6.73 (1H, d, J = 3,2 Hz), 6.75 in-6,87 (2H, m), 7,40-of 7.69 (6H, m), 7,72 (1H, s), 7,86 (1H, s).

IRKBrmaxcm-1: 1684, 1616, 1558, 1522, 1498, 1320.

SIMS (m/z): 412 (M+H)+.

Working example 2. 1-[(1R, 2S)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl]-3-(4-triptoreline)-2(1H,3H)-imidazolone (compound 2).

60% sodium hydride in oil (65 mg) was dispersed in 4 ml of dimethylformamide, to which, while cooling with ice add 118 mg of 1,2,4-triazole.

The mixture is stirred at room temperature for 10 minutes Add a solution of 1-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1 - methylpropyl]-3-(4-triptoreline)-2(1H, 3H)-imidazoline obtained as described in referential example 5, in 2 ml of dimethylformamide, and the mixture is heated at 50oC for 5 h

After cooling, the reaction solution fractionary by adding 8 ml of cold water and 40 mi unite, washed with water and saturated aqueous sodium chloride, dried over magnesium sulfate and the solvent is distilled off under reduced pressure. The residue is purified using chromatography on silica gel (eluent - ethyl acetate:hexane = 1:1 to 2:1 to ethyl acetate) to obtain 350 mg of compound 2 as a white powder.

1H-NMR (CDCl3) : to 1.21 (3H, d, J = 7,2 Hz), 4,19 (1H, d, J = 14,2 Hz) to 5.00 (1H, q, J = 7,2 Hz), 5,11 (1H, d, J = 14,2 Hz), 5,46 (1H, s), of 6.71 (1H, d, J = 3,2 Hz), 6,83 (1H, d, J = 3,2 Hz), 6,72-of 6.90 (2H, m), 7,40-7,56 (1H, m), 7,72 (2H, d, J = 8,4 Hz), of 7.75 (1H, s), 7,83 (2H, d, J = 8,4 Hz), to 7.84 (1H, s).

IRKBrmaxcm-1: 3404, 3383, 3000, 1693, 1618, 1599, 1524, 1500, 1429, 1327.

Calculated, %: C 55,12; H Of 3.78; N 14,61.

C22H18F5N5O2.

Found, %: C 54,81; H Of 3.97; N 14,39.

Working examples 3-19. The following connections will receive the same manner as in working example 2.

Working example 3. 1-[(1R, 2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl]-3-methyl-2(1H,3H)-imidazolone (compound 3), colorless oil. Yield 88 mg (68%).

1H-NMR (CDCl3) : to 1.19 (3H, d, J = 6,8 Hz), of 3.45 (3H, s), 4,69 (1H, d, J = 14,4 Hz), of 5.05 (1H, dd, J = 14,4, and 1.4 Hz), of 5.34 (1H, q, J = 6,8 Hz), the ceiling of 5.60 (1H, s), 6,55 (1H, d, J = 1,6 Hz), only 6.64 (1H, d, J = 1,6 Hz), 6,70-to 6.88 (2H, m), 7,45 to 7.62 (1H, m), of 7.70 (1H, s), of 8.06 (1H, s).

IRneamaxtcm-1: 3113, ITIL - 3-(1H-1,2,4-triazole-1-yl)propyl] -3-(4-forfinal)-2(1H, 3H)-imidazolone (Compound 4), colorless powder. The output of 971 mg (74%).

1H-NMR (CDCl3) : of 1.20 (3H, d, J = 7 Hz), 4,20 (1H, d, J = 14,2 Hz), of 4.95 (1H, q, J = 7 Hz), 5,10 (1H, d, J = 14,2 Hz); to 5.58 (1H, br), 6,60 (1H, d, J = 3,2 Hz), 6,74 (1H, d, J= 3,2 Hz), 6,70-to 6.88 (2H, m), 7,05-7,20 (2H, m), 7,40-the 7.65 (3H, m), 7,73 (1H, s), a 7.85 (1H, s).

IRKBrmaxcm-1: 3147, 3126, 1687, 1618, 1599, 1513.

SIMS (m/z): 430 (M+N)+.

[]2D0-24,8o(C=0.4, CH3OH).

Working example 5. 1-[(1R, 2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -3-(2,4-differenl)-2(1H, 3H)-imidazolone (compound 5), colorless crystalline powder. The output of 416 mg (66%). So pl. 134-136oC.

1H-NMR (CDCl3) : to 1.21 (3H, d, J = 7 Hz), 4,19 (1H, d, J = 14,4 Hz), of 4.95 (1H, q, J = 7 Hz), 5,11 (1H, d, J = 14,4 Hz), 5,52 (1H, br), of 6.52 (1H, t, J = 2,6 Hz), 6,70-6,86 (3H, m), 6,92-7,06 (2H, m), 7,40-to 7.68 (2H, m), 7,74 (1H,s), a 7.85 (1H, s).

IRKBrmaxcm-1: 1693, 1614, 1515, 1428, 1269, 1248.

Working example 6. 2-[(1R, 2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-(4-forfinal)-3(2H, 4H)-1,2,4-triazole (compound 6), colorless powder. The output of 532 mg (53%).

1H-NMR (CDCl3) : of 1.30 (3H, d, J = 7 Hz), 4,36 (1H, d, J = 14,2 Hz), free 5.01 (1H, d, J = 14,2 Hz), to 5.08 (1H, q, J = 7 Hz), 5,44 (1H, s), 6,72-of 6.90 (2H, m), 7,12-7,31 (2H, m), of 7.48-the 7.65 (3H, m), 7,69 (1H, s), 7,76 (1H, s), 7,94 (1H, s).

IRKBrmaxcm-10H17F3N6O2: to 1.21 (3H, d, J = 7,2 Hz), 3,83 (3H, s), is 4.21 (1H, d, J = 14,2 Hz), to 4.92 (1H, q, J = 7,2 Hz), 5,09 (1H, d, J = 14,2 Hz), 5,71 (1H, br), to 6.58 (1H, d, J = 3,2 Hz), of 6.68 (1H, d, J = 3,2 Hz), 6,70-to 6.88 (2H, m), 6,97 (2H, d, J = 9 Hz), 7,40-of 7.60 (1H, m), to 7.50 (2H, d, J = 9 Hz), 7,72 (1H, s), 7,88 (1H, s).

IRKBrmaxcm-1: 3500, 3120, 3000, 1680, 1614, 1516.

SIMS (m/z): 442 (M+H)+.

Working example 8. 1-[(1R, 2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl]-4-(4-methoxyphenyl)-3(2H,4H)-1,2,4-triazole (compound 8), colorless powder. Output 672 mg (65%).

1H-NMR (CDCl3) : of 1.29 (3H, d, J = 7 Hz), 3,85 (3H, s), 4,35 (1H, d, J = 14,4 Hz), 5,02 (1H, d, J = 14,4 Hz), to 5.08 (1H, q, J = 7 Hz), to 5.56 (1H, s), of 6.71-6.89 in (2H, m), 7,01 (2H, d, J = 9 Hz), was 7.45 (2H, d, J = 9 Hz), 7,50-to 7.64 (1H, m), to 7.67 (1H, s), 7,73 (1H, s), of 7.96 (1H, s).

IRKBrmaxcm-1: 3500, 3120, 3080, 1693, 1620, 1562, 1516.

SIMS (m/z): 443 (M+H)+:

Calculated, %: C 54,78; H 4,82; N 18,25.

C21H20F2N6O3: of 1.20 (3H, d, J = 7 Hz), 4,19 (1H, d, J = 14,4 Hz), equal to 4.97 (1H, q, J = 7 Hz), 5,10 (1H, d, J = 14,4 Hz), the 5.51 (1H, br), to 6.39 (1H, d, J = 3,2 Hz), only 6.64 (1H, d, J = 3,2 Hz), 6,70-6,86 (2H, m), 7,31 (2H, d, J = 9 Hz), 7,38-rate of 7.54 (1H, m), of 7.69 (2H, d, J = 9 Hz), 7,74 (1H, s), to 7.84 (1H, s).

IRKBrmaxcm-1: 1691, 1620, 1599, 1514, 1427, 1252.

Working example 10. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-(4-triptoreline)-3(2H, 4H)- 1,2,4-triazole (connection= 15 Hz), 5,09 (1H, q, J = 7,0 Hz), to 5.35 (1H, br), 6,76-6,86 (2H, m), 7,50 to 7.62 (1H, m), 7,66-to 7.84 (5H, m), 7,87 (1H, s), 7,94 (1H, s).

Working example 11. 4-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -2-(4-triptoreline)-3(2H, 4H)- 1,2,4-triazole (compound 11), colorless powder. The output 304 mg (24%).

1H-NMR (CDCl3) : of 1.24 (3H, d, J = 7,2 Hz), 4,15 (1H, d, J = 14 Hz), equal to 4.97 (1H, dq, J = 7,2, 1,4 Hz), to 5.08 (1H, q, J = 14 Hz), to 5.56 (1H, d, J = 1,4 Hz), 6,76-6,91 (2H, m), 7,38-to 7.59 (1H, m), 7,72 (2H, d, J = 8,6 Hz), to 7.77 (1H, s), 7,80 (1H, s), of 8.00 (1H, s), to 8.20 (2H, d, J = 8,6 Hz).

IRKBrmaxcm-1: 3106, 1701, 1618, 1597, 1568, 1520.

Working example 12. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-(4-trifloromethyl)-3(2H, 4H)- 1,2,4-triazole (compound 12), colorless powder. Output: 790 mg (47%).

1H-NMR (CDCl3) : of 1.31 (3H, d, J = 7 Hz), 4,37 (1H, d, J = 14,2 Hz), to 5.03 (1H, d, J = 14,2 Hz), 5,09 (1H, q, J = 7 Hz), 5,41 (1H, s), 6,76-of 6.90 (2H, m), 7,38 (2H, d, J = 9 Hz), 7,51-to 7.64 (1H, m), the 7.65 (2H, d, J = 9 Hz), of 7.70 (1H, s), 7,81 (1H, s), 7,94 (1H, s).

IRKBrmaxcm-1: 1711, 1620, 1562, 1516, 1500, 1427, 1259, 1209.

Working example 13. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] 3-(4-isopropylphenyl)-2(1H, 3H)-imidazolone (compound 13), colorless powder. Yield 200 mg (84%).

1H-NMR (CDCl3) : to 1.21 (3H, d, J = 7 Hz), of 1.26 (6H, d, J = 6,8 Hz), to 2.94 (1H, q, J = 6,8 Hz), 4,19 (1H, d, J = 14 Hz), to 4.92 (1H, m), (1H, s).

Working example 14. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-(2,4-differenl)-3(2H, 4H)-1,2,4-triazole (compound 14), colorless powder. T. pl. 111-113oC. Yield 660 mg (47%).

1H-NMR (CDCl3) : of 1.32 (3H, d, J = 7 Hz), 4,36 (1H, d, J = 14,4 Hz), 5,04 (1H, d, J = 14,4 Hz), 5,07 (1H, q, J = 7 Hz), 5,73 (1H, s), 6,74-to 6.88 (2H, m), 7,00-7,14 (2H, m), 7,50 to 7.75 (2H, m), 7,71 (1H, s), 7,73 (1H, d, J = 2,4 Hz), 7,95 (1H, s).

IRKBrmaxcm-1: 1711, 1614, 1554, 1515, 1500, 1439, 1333, 1273.

Working example 15. 4-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -2-(4-forfinal)-3(2H, 4H)-1,2,4-triazole (compound 15), colorless powder. The output of 545 mg (55%).

1H-NMR (CDCl3) : of 1.23 (3H, d, J = 7,2 Hz), 4,15 (1H, d, J = 14,2 Hz), of 4.95 (1H, dq, J = 7,2, 1,6 Hz), to 5.08 (1H, d, J = 14,2 Hz), to 5.56 (1H, d, J = 1,6 Hz), 6,78-6,91 (2H, m), 7,14 (2H, t, J = 9,4 Hz), 7,39 to 7.62 (1H, m), to 7.77 (1H, s), 7,80 (1H, s), 7,95 (1H, s), to 7.99 (2H, dd, J = 9,4, 4,8 Hz).

IRKBrmaxcm-1: 3093, 1691, 1620, 1599, 1566, 1512.

Working example 16. By the same method as in working example 2, was carried out by reaction with a mixture of about 1:1 2-[(1R,2S)-2-(2,4-differenl)-2,3-epoxy-1-methylpropyl] -4-(4-isopropylphenyl)- 3(2H,4H)-1,2,4-triazolone and (1R)-1-[(2R)-2-(2,4-differenl)- 2-oxiranyl]ethanol obtained in reference example 20, obtaining 2-((1R,2R)-2-(2,4-differenl)-2-hydroxy-1-IU the and.

1H-NMR (CDCl3) : of 1.28 (6H, d, J = 6,8 Hz), (3H, d, J = 7 Hz), 2,97 (1H, q, J = 6,8 Hz), 4,35 (1H, d, J = 14 Hz), to 5.03 (1H, d, J = 14 Hz), 5,10 (1H, q, J = 7 Hz), of 5.55 (1H, s), 6,76-6,87 (2H, m), 7,37 (2H, d, J = 8,8 Hz), 7,47 (2H, d, J = 8,8 Hz), 7,50 to 7.62 (1H, m), 7,68 (1H, s), to 7.77 (1H, s), of 7.96 (1H, s).

Calculated, %: C 60,79; H 5,32; N Be 18.49.

C23H24F2N6O2.

Found, %: C 60,48; H 5,49; N 18,32.

Working example 17. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl]-4-(4-triptoreline)-5(1H,4H)-tetrazole (compound 18), colorless powder. The output of 21%.

1H-NMR (CDCl3) : of 1.47 (3H, d, J = 7,2 Hz), 4,36 (1H, d, J = 14,2 Hz), to 5.08 (1H, d, J = 14,2 Hz), 5,10 (1H, q, J = 7,2 Hz), vs. 5.47 (1H, s), 6,74-6,91 (2H, m), 7,50-to 7.68 (1H, m), 7,73 (1H, s), 7,80 (2H, d, J = 8,8 Hz), to $ 7.91 (1H, s), 8,18 (2H, d, J = 8,8 Hz).

Calculated, %: C 49,90; H 3,35; N 20,37.

C20H16F5N7O2.

Found, %: C 49,64; H 3,35; N 20,22.

Working example 18. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] - 2(1H,3H)-imidazolone (compound 19), colorless powder. Yield 79%.

1H-NMR (CDCl3) : of 1.20 (3H, d, J = 7 Hz), 4,20 (1H, d, J = 14 Hz), 4,37 (2H, t, J = 12 Hz), 4,94 (1H, q, J = 7 Hz), 5,09 (1H, d, J = 14 Hz), 5,55-5,74 (1H, br), the 6.06 (1H, tt, J = 5, 53 Hz), 6,59 (1H, d, J = 3 Hz), 6,72 (1H, d, J = 3 Hz), 6,74-6,85 (2H, m), 7,01 (2H, d, J = 9 Hz), 7,42-of 7.55 (1H, m), 7,58 (2H, d, J = 9 Hz), 7,73 (1H, s), 7,86 (1H, s). So Is B>.

Found, %: C 53,12; H 4,19; N 12,76.

[]2D0- 17,9o(C=0.3, AND CH3OH).

Working example 19. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(4-benzyl-1-piperazinil)phenyl]- 3(2H, 4H)-1,2,4-triazole (compound 21), colorless powder. Yield 59%.

1H-NMR (CDCl3) : of 1.28 (3H, d, J = 7 Hz), 2,62 (4H, t, J = 4,8 Hz) at 3.25 (4H, t, J = 4,8 Hz) and 3.59 (2H, s), 4,33 (1H, d, J = 14,2 Hz), free 5.01 (1H, d, J = 14,2 Hz), to 5.08 (1H, q, J = 7 Hz), ceiling of 5.60 (1H, s), 6,72-6,91 (2H, m), 6,98 (2H, d, J = 9 Hz), 7.23 percent was 7.45 (7H, m), 7,45 to 7.62 (1H, m), 7,66 (1H, s), 7,71 (1H, s), of 7.96 (1H, s).

Calculated, %: C 62,51; H 5,58; N 18,81.

C31H32F2N8O2: of 1.29 (3H, d, J = 7 Hz), of 2.16 (3H, s), 3,15-to 3.35 (4H, m), 3,59-3,88 (4H, m), 4,35 (1H, d, J = 14,4 Hz), free 5.01 (1H, d, J = 14,4 Hz), to 5.08 (1H, q, J = 7 Hz), to 5.57 (1H, s), 6.75 in-6,90 (2H, m), 7,01 (2H, d, J = 9 Hz), 7,44 (2H, d, J = 9 Hz), 7,49-to 7.67 (1H, m), 7,68 (1H, s), 7,73 (1H, s), 7,98 (1H, s).

Calculated, %: C 55,20; H 5,52; N 19,81.

C26H28F2N8O3: of 1.29 (3H, d, J = 7 Hz), 3,18-3,30 (4H, m), 3,30-of 3.46 (4H, m), with 3.79 (3H, s), 4,35 (1H, d, J = 14,4 Hz), free 5.01 (1H, d, J = 14,4 Hz), 5,09 (1H, q, J = 7 Hz), 5,59 (1H, s), 6,72-of 6.90 (2H, m), 6.87 in (2H, d, J = 9,2 Hz), 6,97 (2H, d, J = 9,2 Hz), 7,06 (2H, d, J = 9,2 Hz), the 7.43 (2H, d, J = 9,2 Hz), 7,50-7,66 (1H, m), 7,68 (1H, s), 7,73 (1H, s), of 7.97 (1H, s).

Calculated, %: C 61,78; H 5,35; N 18,59.

C31H32F2N8O3.

Found, %: C 61,45; H Lower Than The 5.37; N 18,29.

Working example 22. 2-[(1R 25), colorless powder. A 30% yield.

1H-NMR (CDCl3) : of 1.32 (3H, d, J = 7,0 Hz), 4,36 (1H, d, J = 14,6 Hz), 5,04 (1H, d, J = 14,6 Hz), 5,09 (1H, q, J = 7,0 Hz), are 5.36 (1H, s), 6,76-6,86 (2H, m), of 7.5 to 7.7 (4H, m), 7,78-of 7.90 (2H, m), 7,86 (1H, s), to 7.93 (1H, s).

Calculated, %: C 52,50; H 3,57; N 17,49.

C21H17F5N6O2.

Found, %: C 52,64; H 3,72; N 17,15.

Working example 23. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-(4-forfinal)-5(1H, 4H)-tetrazole (compound 26), colorless powder. Yield 51%.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7,2 Hz), 4,35 (1H, d, J = 14,4 Hz), to 5.08 (1H, d, J = 14,4 Hz), 5,10 (1H, q, J = 7,2 Hz), of 5.50 (1H, s), 6,72-of 6.90 (2H, m), 7,15-7,30 (2H, m), 7,50-to 7.68 (1H, m), 7,72 (1H, s), to $ 7.91 (1H, s), 7,89 shed 8.01 (2H, m).

Calculated, %: C 50,78; H Of 4.04; N 21,82.

C19H16F3N7O2: of 1.36 (3H, d, J = 7,2 Hz), 4,37 (1H, d, J = 14,2 Hz), free 5.01 (1H, d, J = 14,2 Hz), 5,07 (1H, q, J =7,2 Hz), 5,31 (1H, s), 6,74-of 6.90 (2H, m), 7,50-the 7.65 (1H, m), to 7.67 (1H, s), of 7.69 (1H, s), of 7.70 (1H, s), to 7.93 (2H, d, J = 5,8 Hz), the rate of 8.75 (2H, d, J = 5,8 Hz).

Calculated, %: C 51,82; H 4,58; N 22,26.

C19H17F2N7O2: of 1.41 (3H, d, J = 6,6 Hz), 4,32 (1H, d, J = 11,6 Hz), 4,78 (1H, q, J = 6,6 Hz), the 4.90 (1H, d, J= 11,6 Hz), 5,41 (1H, s), 6,70-6,92 (2H, m), 7,44 (1H, s), 7,89 (1H, dd, J = 5,6 Hz to 1.2 Hz), the 7.85-of 8.06 (1H, m), 8,15 (1H, s), of 8.90 (1H, d, J = 5,6 Hz), 9,10 (1H, d, J = 1,2 Hz), 9,26 (1H, s).

Calculated, %: C 51,06; H Of 4.05; N 26,47.

C18H16F2N8O7,0 (1H, m), 7,63 (1H, s), of 7.70 (1H, s), to 7.93 (1H, s).

The specified connection is treated with a solution of 4n. hydrochloric acid-ethyl acetate to obtain hydrochloride as colorless powder.

IR(KBr)cm-1: 1716, 1700, 1689, 1652, 1618, 1560, 1506.

Working example 27. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,3,3-tetrafluoropropoxy)-phenyl] - 3(2H,4H)-1,2,4-triazole (compound 30), colorless powder. Yield 63%.

So pl. 150-151oC (isopropyl ether).

IRKbrmaxcm-1: 1716, 1697, 1618, 1558, 1517, 1506.

1H-NMR (CDCl3) : of 1.30 (3H, d, J = 7 Hz), 4,37 (1H, d, J = 15 Hz), and 4.40 (2H, tt, J = 11,8, 1,4 Hz) 5,02 (1H, d, J = 15 Hz), vs. 5.47 (1H, s), 5,09 (1H, q, J = 7 Hz), 6,07 (1H, tt, J = 53 Hz and 4.8 Hz), 6.75 in-to 6.88 (2H, m), 7,07 (2H, dt, J = 9 Hz and 2.2 Hz), 7,53 (2H, dt, J = 9 Hz and 2.2 Hz), 7,50-to 7.64 (1H, m), 7,69 (1H, s), of 7.75 (1H, s), 7,95 (1H, s).

Calculated, %: C 50,93; H 3,72; N 15,49.

C23H20F6N6O3.

Found, %: C 50,91; H 3,84; N 15,47.

Working example 28. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-(2-triptoreline)-3(2H, 4H)- 1,2,4-triazole (compound 31), colorless powder. Yield 28%.

1H-NMR (CDCl3) : of 1.32 (3H, d, J = 7 Hz), 4,29 (1H, d, J = 14,2 Hz), is 5.06 (1H, d, J = 14,2 Hz), 5,07 (1H, q, J = 7 Hz), 5,41 (1H, s), 6,74-6,86 (2H, m), of 7.48-of 7.60 (3H, m), 7,63-of 7.90 (3H, m), of 7.70 (1H, s), of 7.97 (1H, s).

Working example 29. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-(4-isopropoxyphenyl)-3(2H, 4H)-triazole (compound 32), colorless powder. Yield 80%.

1H-NMR (CDCl3) : of 1.29 (3H, d, J = 7,0 Hz), of 1.36 (6H, d, J = 6 Hz), 4,35 (1H, d, J = 14,2 Hz), 4,58 (1H, septet, J =6 Hz), 5,02 (1H, d, J = 14,2 Hz), to 5.08 (1H, q, J = 7 Hz), to 5.57 (1H, s), 6,72-6,89 (2H, m), of 6.99 (2H, d, J = 9 Hz), 7,42 (2H, d, J = 9 Hz), 7,47-7,63 (1H, m), to 7.67 (1H, s), 7,72 (1H, s), of 7.96 (1H, s).

Calculated, %: C 56,55; H Are 5.36; N 17,20.

C23H24F2N6O3: 0,99 (6H, d, J = 6,2 Hz) of 1.23 (3H, d, J = 6,8 Hz), 1.56 to of 1.80 (3H, m), and 3.72 (2H, t, J = 7,2 Hz), 4,20 (1H, d, J = 14,2 Hz), equal to 4.97 (1H, d, J = 14,2 Hz), 5,02 (1H, q, J = 6,8 Hz), 5,63 (1H, s), 6,72-of 6.90 (2H, m), 7,45 to 7.62 (1H, m), 7,50 (1H, s), to 7.67 (1H, s), of 7.96 (1H, s).

SIMS (m/z): 407 (M+H)+.

Working example 31. 2-[1R, 2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl]-4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]- 3(2H, 4H)-1,2,4-triazole (compound 34), colorless powder. Yield 65%.

IR cm-1(KBr): 1710, 1691, 1620, 1564, 1511, 1276.

1H-NMR (CDCl3) : of 1.31 (3H, d, J = 7 Hz), 4,37 (1H, d, J = 14,2 Hz), 5,02 (1H, d, J = 14,2 Hz), 5,09 (1H, q, J = 7 Hz), 5,41 (1H, s), 5,94 (1H, tt, J = 53 Hz, J = 2,8 Hz), 6.75 in-6,90 (2H, m), 7,38 (2H, d, J = 9 Hz), 7,50-of 7.70 (1H, m), 7,63 (3H, d, J = 9 Hz), of 7.70 (1H, s), 7,80 (1H, s), 7,94 (1H, s).

Working example 32. 2-(4-Chlorophenyl)-4-1(1R,2R)-2-(2,4-differenl)- 2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)prop 7,2 Hz), to 4.14 (1H, d, J = 14,2 Hz), of 4.95 (1H, dq, J = 7,2 Hz to 1.6 Hz), 5,07 (1H, d, J = 14,2 Hz), 5,54 (1H, d, J = 1,6 Hz), 6.73 x-6,89 (2H, m), 7,37 is 7.50 (1H, m), 7,41 (2H, d, J = 9 Hz), to 7.77 (1H, s), to 7.93 (1H, s), of 7.96 (1H, s), 7,98 (2H, d, J = 9 Hz).

Calculated, %: C 53,76; H 3,83; N 18,81.

C20H17ClF2N6O2.

Found, %: C 53,93; H 4,00; N 18,44.

Working example 33. 4-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -2-(4-trifloromethyl)-3(2H, 4H)- 1,2,4-triazole (compound 36), colorless powder. Yield 68%.

1H-NMR (CDCl3) : of 1.24 (3H, d, J = 7,2 Hz), 4,14 (1H, d, J = 14,4 Hz), 4,96 (1H, dq, J = 7,2, 1,6 Hz), to 5.08 (1H, d, J = 14,4 Hz), to 5.56 (1H, d, J = 1,6 Hz), 6.75 in-6,90 (2H, m), 7,31 (2H, d, J = 9,2 Hz), of 7.48-7,52 (1H, m), to 7.77 (1H, s), 7,80 (1H, s), of 7.97 (1H, s), 8,08 (2H, d, J = 9,2 Hz).

Working example 34. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-(4-trifloromethyl)-5(1H, 4H)-tetrazole (compound 37), colorless powder. Yield: 43%.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7,2 Hz), 4,35 (1H, d, J = 13,8 Hz), to 5.08 (1H, d, J = 13,8 Hz), 5,10 (1H, q, J =7,2 Hz), the 5.51 (1H, s), of 6.71-of 6.90 (2H, m), 7,38 (2H, d, J = 9,2 Hz), of 7.48-7,63 (1H, m), 7,72 (1H, s), to $ 7.91 (1H, s), of 8.04 (2H, d, J = 9,2 Hz).

IRKBrmaxcm-1: 3400, 3010, 1722, 1684, 1618, 1599, 1510.

[]2D0-5,7o(C=1, methanol).

Working example 35. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4- 1H-NMR (CDCl3) : of 1.45 (3H, d, J = 7,2 Hz), 4,35 (1H, d, J = 14,2 Hz) to 4.41 (2H, t, J = and 11.8 Hz), to 5.08 (1H, d, J = 14,2 Hz), 5,11 (1H, q, J = 7,2 Hz), of 5.53 (1H, s), 6,09 (1H, tt, J = 53,2, 4,8 Hz), 6.75 in-6,90 (2H, m), was 7.08 (2H, d, J = 9 Hz), 7,50-to 7.68 (1H, m), 7,72 (1H, s), of 7.90 (2H, d, J = 9 Hz), 7,92 (1H, s).

IRKBrmaxcm-1: 3400, 3050, 1726, 1618, 1599, 1516, 1423.

[]2D0-2,3o(C=0.4, methanol).

Working example 36. 1-(4-Chlorophenyl)-4-[(1R,2R)-2-(2,4-differenl)- 2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -5 (1H, 4H)-tetrazole (compound 39), colorless powder. Yield 46%.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7 Hz), 4,35 (1H, d, J = 14,4 Hz), to 5.08 (1H, d, J = 14,4 Hz), 5,10 (1H, q, J = 7 Hz), 5,49 (1H, s), 6,72-6,91 (2H, m), 7,42-to 7.61 (1H, m), to 7.50 (2H, d, J = 9 Hz), 7,72 (1H, s), 7,92 (1H, s), 7,94 (2H, d, J = 9 Hz).

IRKBrmaxcm-1; 3450, 3090, 1726, 1618, 1599, 1497.

Calculated, %: C 49,95; H 3,75; N 21,46.

C19H16ClF2N7O2]2D0-3,2o(C = 0.5, methanol)

Working example 37. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]- 2(1H, 3H)-imidazolone (compound 40), colorless powder. Yield 66%.

1H-NMR (CDCl3) : to 1.21 (3H, d, J = 7 Hz), 4,18 (1H, d, J = 14 Hz), equal to 4.97 (1H, q, J = 7 Hz), 5,10 (1H, d, J = 14 Hz), 5,4-5,6 (1H, br), to 5.93 (1H, tt, J = 53, 2,8 Hz), only 6.64 (1H, d, J = 3 Hz), 6,77 (1H, d, J = 3 Hz), 6,74-6,84 (2H, m), 7,30 (2H, d, J = 9 Hz), 7,40-of 7.55 (1H, m), to 7.67 (2H, SUB>3.

Found, %: C 52,22; H 3,83; N 13,08.

[]2D0-18,4o(C = 0.6, methanol).

Working example 38. 1-(4-Chlorophenyl)-3-[(1R,2R)-2-(2,4-differenl)- 2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -2(1H, 3H)-imidazolone (compound 41), colorless powder. Yield 54%.

1H-NMR (CDCl3) : of 1.20 (3H, d, J = 7 Hz), 4,19 (1H, d, J = 14 Hz), equal to 4.97 (1H, q, J = 7 Hz), 5,10 (1H, d, J = 14 Hz), 5,42-the 5.65 (1H, br), 6,63 (1H, d, J = 3,2 Hz), to 6.75 (1H, d, J = 3,2 Hz), 6,78-6,85 (2H, m), 7,42 (2H, d, J = 9 Hz), 7,40-of 7.55 (1H, m), to 7.61 (2H, d, J = 9 Hz), 7,74 (1H, s), a 7.85 (1H, s).

Working example 39. 4-(4-Chlorophenyl)-2-[(1R,2R)-2-(2,4-differenl)- 2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -3(2H, 4H)-1,2,4-triazole (compound 42), colorless powder. Yield 42%.

1H-NMR (CDCl3) : of 1.30 (3H, d, J = 7,0 Hz), 4,36 (1H, d, J = 14 Hz), 5,02 (1H, d, J = 14 Hz), to 5.08 (1H, q, J = 7,0 Hz), 5,41 (1H, s), 6.75 in-6,86 (2H, m), 7,47-7,63 (5H, m), of 7.70 (1H, s), 7,79 (1H, s), 7,94 (1H).

Working example 40. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -3-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl] - 2-(1H,3H)-imidazolone (compound 43), colorless powder. Yield 74%.

1H-NMR (CDCl3) ; of 1.20 (3H, d, J = 7,0 Hz), 4,20 (1H, d, J = 14,3 Hz), of 4.49 (2H, t, J = 13 Hz), 4,94 (1H, q, J = 7,0 Hz), 5,09 (1H, d, J = 14,3 Hz), 5,5-5,7 (1H, br), 6,09 (1H, tt, J = 52, of 5.4 Hz), 6,59 (1H, d, J = 3,2 Hz), 6,72 (1H, d, J = 3,2 Hz), 6.75 in-6,85 (2H, m), 7,03 (2H, d, J = 9,0 Hz), 7,42-rate of 7.54 (1H, m), 7,58 (2H, d, J = 9,0 Hz), 7,73 (1H, s), a 7.85 (1H, s).

1H-NMR (CDCl3) : to 1.21 (3H, d, J = 6,8 Hz), 4,20 (1H, d, J = 14,2 Hz), to 4.38 (2H, q, J = 8 Hz), of 4.95 (1H, q, J = 6,8 Hz), 5,10 (1H, d, J = 14,2 Hz), the ceiling of 5.60 (1H, br), 6,60 (1H, d, J = 3 Hz), was 6.73 (1H, d, J = 3 Hz), 6,70-to 6.88 (2H, m), 7,03 (2H, d, J = 9 Hz), 7,40-of 7.55 (1H, m), 7,58 (2H, d, J = 9 Hz), 7,73 (1H, s), 7,86 (1H, s).

Working example 42. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -3-[4-(2,2,3,3,3-pentafluoropropane)phenyl] - 2(1H, 3H)-imidazolone (compound 45), colorless crystalline powder. Yield 79%.

1H-NMR (CDCl3) : to 1.21 (3H, d, J = 7 Hz), 4,20 (1H, d, J = 14,2 Hz), of 4.45 (2H, t, J = 12 Hz), of 4.95 (1H, q, J = 7 Hz), 5,10 (1H, d, J = 14,2 Hz), the ceiling of 5.60 (1H, br), 6,60 (1H, d, J = 3 Hz), 6,74 (1H, d, J = 3 Hz), 6,65-6,85 (2H, m), 7,03 (2H, d, J = 8,8 Hz), 7,40-of 7.55 (1H, m), to 7.59 (2H, d, J = 8,8 Hz), 7,74 (1H, s), 7,86 (1H, s).

Working example 43. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,2-triptoreline)phenyl]-3(2H,4H)- 1,2,4-triazole (compound 46), colorless needles. Yield 59%.

1H-NMR (CDCl3) : of 1.30 (3H, d, J = 7 Hz), 4,36 (1H, d, J = 14,8 Hz) to 4.41 (2H, q, J = 8 Hz), 5,02 (1H, d, J = 14,8 Hz), 5,09 (1H, q, J = 7 Hz), of 5.48 (1H, s), 6,74-of 6.90 (2H, m), to 7.09 (2H, d, J = 9 Hz), of 7.48-the 7.65 (1H, m), 7,53 (2H, d, J = 9 Hz), 7,69 (1H, s), 7,76 (1H, s), 7,95 (1H, s).

Working example 44. 2- [(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,3,3,3-pentafluoropropane)phenyl] - 3(2H,4H)-1,2,4-triazole (compound 47), bestwe the 5,09 (1H, q, J = 7 Hz), of 5.48 (1H, s), 6.75 in-6,90 (2H, m), to 7.09 (1H, d, J = 9 Hz), of 7.48-to 7.64 (1H, m), 7,54 (2H, d, J = 9 Hz), of 7.70 (1H, s), 7,76 (1H, s), 7,95 (1H, s).

Working example 45. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,3,3,4,4,5,5-octadecenoic)phenyl] - 3(2H, 4H)-1,2,4-triazole (compound 48), colorless powder. Yield 54%.

1H-NMR (CDCl3) : of 1.30 (3H, d, J = 7,0 Hz), 4,36 (1H, d, J = 14 Hz), to 4.52 (2H, t, J = 13 Hz), free 5.01 (1H, t, J = 14 Hz), 5,09 (1H, q, J = 7,0 Hz), of 5.48 (1H, s), 6,10 (1H, tt, J = 52, of 5.4 Hz), 6,77-6,87 (2H, m), to 7.09 (2H, d, J = 9,0 Hz), 7,51 to 7.62 (1H, m), 7,54 (2H, d, J = 9,0 Hz), of 7.70 (1H, s), 7,76 (1H, s), 7,95 (1H, s).

Working example 46. (4-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -2-[4-(2,2,2-triptoreline)phenyl]-3(2H,4H)- 1,2,4-triazole (compound 49), colorless powder. Yield 68%.

1H-NMR : 1,24 (3H, d, J = 7,2 Hz), 4,15 (1H, d, J = 14,2 Hz), 4,39 (2H, q, J = 8,2 Hz), of 4.95 (1H, dq, J = 7,2, 1,6 Hz), 5,09 (1H, d, J = 14,2 Hz), to 5.56 (1H, d, J = 1,6 Hz), 6,70-of 6.90 (2H, m), 7,03 (2H, d, J = 9,2 Hz), 7,34-7,53 (1H, m), to 7.77 (1H, s), 7,81 (1H, s), 7,94 (1H, s), of 7.96 (2H, d, J = 9,2 Hz).

Working example 47. 4-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -2-[4-(2,2,3,3,3-pentafluoropropane)phenyl] - 3(2H,4H)-1,2,4-triazole (compound 50), colorless powder. Yield 53%.

1H-NMR (CDCl3) : of 1.24 (3H, d, J = 7,2 Hz), 4,14 (1H, d, J = 14,4 Hz), of 4.45 (2H, t, J = and 12.2 Hz), of 4.95 (1H, dq, J = 7,2, 1,6 Hz), to 5.08 (1H, d, J = 14,4 Hz), 5,54 (1H, d, J = 1,6 Hz), of 6.71-6.89 in (2H, m), 7,03 (2H, d, J = 9 Hz), 1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -2-[4-(2,2,3,3,4,4,5,5- octadecenoic)phenyl] -3(2H,4H)-1,2,4-triazole (compound 51), colorless powder. Yield 37%.

1H-NMR (CDCl3) : of 1.24 (3H, d, J = 7 Hz), 4,14 (1H, d, J = 14,4 Hz), of 4.49 (2H, t, J = 13 Hz), 4,94 (1H, dq, J = 1,6 Hz), to 5.08 (1H, d, J = 14,4 Hz), 5,54 (1H, d, J = 1,6 Hz), 6,10 (1H, tt, J = 52 Hz, a 5.4 Hz), of 6.71-6.89 in (2H, m), 7,03 (2H, d, J = 9,2 Hz), 7,34-7,51 (1H, m), to 7.77 (1H, s), 7,80 (1H, s), to 7.93 (1H, s), 7,95 (2H, d, J = 9,2 Hz).

Working example 49. 4-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazol-1-yl)propyl] -2-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] - 3(2H,4H)-1,2,4-triazole (compound 52), colorless powder. Yield 81%.

1H-NMR (CDCl3) : of 1.23 (3H, d, J = 7 Hz), 4,14 (1H, d, J = 14,4 Hz), of 4.49 (2H, t, J = 13 Hz), 4,94 (1H, dq, J = 7, 1,6 Hz), to 5.08 (1H, d, J = 14,4 Hz), 5,54 (1H, d, J = 1,6 Hz), 6,10 (1H, tt, J = 52, of 5.4 Hz), of 6.71-6.89 in (2H, m), 7,03 (2H, d, J = 9,2 Hz), 7,34-7,51 (1H, m), to 7.77 (1H, s), 7,80 (1H, s), to 7.93 (1H, s), 7,95 (2H, d, J = 9,2 Hz).

Working example 50. 4-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl]-2-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]- 3(2H, 4H)-1,2,4-triazole (compound 53), colorless powder. Yield 57%.

1H-NMR (CDCl3) : of 1.24 (3H, d, J = 7,2 Hz), 4,14 (1H, d, J = 14,2 Hz), of 4.95 (1H, dq, J = 7,2, 1,6 Hz), to 5.08 (1H, d, J = 14,2 Hz), of 5.55 (1H, d, J = 1,6 Hz), to 5.93 (1H, tt, J = 53, 2,8 Hz), of 6.71-of 6.90 (2H, m), 7,30 (2H, d, J = 9,2 Hz), 7,34-7,51 (1H, m), to 7.77 (1H, s), 7,80 (1H, s), of 7.96 (1H, s), of 8.06 (2H, d, J = 9,2 Hz).

Working example 51. 60% sodium hydride in oil (80 mg) was dispersed in 5 ml of dimethylformamide and 582 mg of 4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H, 4H)-1,2,4-triazolone dobell-differenl)-2-(1H-1,2,4 - triazole-1-yl)methyloxirane (synthesized according to the method of Japan patent Laid-Open Sho 58-32868) and the resulting mixture is heated at 60oC within 15 minutes After cooling the reaction solution fractionary by adding 20 ml of cold water and 40 ml of ethyl acetate, and cooled aqueous layer was extracted twice with ethyl acetate. An ethyl acetate layers are combined, washed with water and saturated aqueous sodium chloride, dried over magnesium sulfate and distilled under reduced pressure. The residue is purified using chromatography on silica gel (eluent - dichloromethane:acetone = 2:1) to give 510 mg of 2-[(2RS)-2-(2,4-differenl)-2-hydroxy-3-(1H-1,2,4-triazole - 1-yl)propyl] -4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (compound 54) in the form of a white powder.

1H-NMR (CDCl3) : 4,18 (1H, d, J = 15 Hz), and 4.40 (2H, t, J = 12 Hz), br4.61 (1H, d, J = 15 Hz), 4,71 (2H, s), 5,80 (1H, s), equal to 6.05 (1H, tt, J = 5,2, 54 Hz), 6,77-6,87 (2H, m), 7,01 (2H, d, J = 8,6 Hz), 7,37 (2H, d, J = 8,6 Hz), 7,53 (1H, s), 7,56-to 7.64 (1H, m), to 7.84 (1H, s), 8,15 (1H, s). So pl. 79-80oC.

Working example 52. 60% sodium hydride in oil (40 mg) was dispersed in 4 ml of dimethylformamide and 250 mg of 2-(4-trifloromethyl)-3(2H,4H)-1,2,4-triazolone added under ice cooling. The mixture is stirred at room temperature for 10 minutes

To the mixture is added 237 mg of (2RS)-2-(2,4-differenl)-2-(1H-1,2,4-triazole - 1-yl)methyloxirane and the resulting mixture was stirred at room temperature for 22 hours After Oh the first layer extracted twice with ethyl acetate. An ethyl acetate layers are combined, washed with water and saturated aqueous sodium chloride, dried over magnesium sulfate and distilled under reduced pressure. The residue is purified using chromatography on silica gel (eluent - ethyl acetate:hexane = 3:1 to ethyl acetate) to obtain 92 mg of 4-[(2RS)-2-(2,4-differenl)-2-hydroxy-3-(1H-1,2,4-triazole-1-yl)propyl]- 2-(4-trifloromethyl)-3(2H,4H)-1,2,4-triazolone (compound 55) in the form of a white powder.

1H-NMR (CDCl3) : 4,20 (2H, s), 4,51 (1H, d, J = 14,4 Hz), 4,80 (1H, d, J = 14,4 Hz), to 5.93 (1H, s), 6,80-6,89 (2H, m), 7,31 (2H, d, J = 9,2 Hz), 7,51-to 7.59 (1H, m), to 7.61 (1H, s), 7,87 (1H, s), 7,92 (2H, d, J = 9,2 Hz), with 8.05 (1H, s).

So pl. 128-130oC.

Working example 53. By the same method as in working example 51 according to 0.19 g of (2RS)-2-(2,4-Differenl)-2-(1-imidazolyl)methyloxirane and 0.23 g of 4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -3(2H,4H)-1,2,4-triazolone get 2-[(2RS)-2-(2,4-differenl)-2-hydroxy-3-(1-imidazolyl)propyl] - 4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] -3(2H,4H)-1,2,4-triazolone (compound 56: 0,23 g) as colorless powder. Yield 55%.

1H-NMR (CDCl3) : 4,20 (1H, d, J = 15 Hz), 4,37 (2H, s), 4,37 (2H, t, J = 12 Hz), of 4.57 (1H, d, J = 15 Hz), USD 5.76 (1H, s), 6,04 (1H, tt, J = 5,2 Hz 54 Hz), 6.75 in-6,98 (2H, m), 6,92 (1H, s), 7,00 (2H, d, J = 9,2 Hz), 7,26 (1H, s), 7,35 (2H, d, J = 9,2 Hz), 7,43-of 7.60 (1H, m), 7,45 (1H, s), 7,51 (1H, s).

Working example 54. The same method is eraftineense)phenyl] -3(2H,4H)-1,2,4-triazolone get 2-[(2R)-2-(2,4-differenl)-2-hydroxy-3-(1H-1,2,4-triazole - 1-yl)propyl] -4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl] -3(2H, 4H)-1,2,4-triazolone (compound 78: 0,22 g) as colorless powder. Yield 43%.

1H-NMR (CDCl3) : 4,19 (1H, d, J = 15 Hz), br4.61 (1H, q, J = 15 Hz), 4.72 in (2H, s), 5,71 (1H, s), of 5.92 (1H, tt, J = 2,8 Hz 53 Hz), 6,76-to 6.88 (2H, m), 7,31 (2H, d, J = 10 Hz), 7,46-to 7.64 (1H, m), 7,49 (2H, d, J = 10 Hz), to 7.59 (1H, s), to 7.84 (1H, s), 8,14 (1H, s).

Working examples 55-61. The following compounds were obtained in accordance with the method described in working example 54.

Working example 55. 2-[(2R)-2-(2,4-Differenl)-2-hydroxy-3-(1H - 1,2,4-triaal-1-yl)propyl] -4-[4-(2,2,2-triptoreline)phenyl] -3(2H, 4H)- 1,2,4-triazole (compound 90), colorless powder. A 30% yield.

1H-NMR (CDCl3) : 4,18 (1H, d, J = 15 Hz), 4,37 (2H, q, J = 8 Hz), 4,60 (1H, d, J = 15 Hz), 4,71 (2H, s), 5,79 (1H, s), 6,77-6,98 (2H, m), 7,02 (2H, d, J = 10 Hz), 7,37 (2H, d, J = 10 Hz), 7,46-to 7.64 (1H, m), 7,53 (1H, s), to 7.84 (1H, s), 8,15 (1H, s).

Working example 56. 2-[(2R)-2-(2,4-Differenl)-2-hydroxy-3-(1H - 1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,3,3,3-pentafluoropropane)phenyl] - 3(2H, 4H)-1,2,4-triazole (compound 94), colorless powder. Yield 31%.

1H-NMR (CDCl3) : 4,18 (1H, d, J = 15 Hz), of 4.44 (2H, t, J = 12 Hz), 4,60 (1H, d, J = 15 Hz), 4,71 (2H, s), 5,79 (1H, s), 6,77-6,86 (2H, m), 7,02 (2H, d, J = 8,8 Hz), 7,38 (2H, d, J = 8,8 Hz), 7,53 (1H, s), 7,56-to 7.64 (1H, m), to 7.84 (1H, s), 8,15 (1H, s).

[]2D0+13,5 (C = 1.0, methanol)

Working example 57. 4-[(2S)-2-(2,4-Differenl)-2-hydroxy-3-(1H - 1,2,4-triazole-1-yl)propyl] -2->H-NMR (CDCl3) : 4,14 (1H, d, J = 15 Hz), 4,24 (1H, d, J = 15 Hz), 4,32 (2H, t, J = 12 Hz), 4,51 (1H, d, J = 15 Hz), of 4.77 (1H, d, J = 15 Hz), of 6.02 (1H, s), the 6.06 (1H, tt, J = 4,8 Hz 54 Hz), of 6.71-6,98 (2H, d, J = 9,2 Hz), 7,03 (2H, d, J = 9,2 Hz), 7,51-7,63 (1H, m), 7,55 (1H, s), 7,79 (2H, d, J = 9,2 Hz), 7,86 (1H, s), of 8.06 (1H, s).

Working example 58. 4-[(2S)-2-(2,4-Differenl)-2-hydroxy-3-(1H - 1,2,4-triazole-1-yl)propyl] -2-[4-(1,1,2,2-tetrafluoroethoxy)phenyl] -3-(2H,4H)- 1,2,4-triazole (compound 79), colorless powder. Yield 23%.

1H-NMR (CDCl3) : 4,15 (1H, d, J = 14 Hz), 4,24 (1H, d, J = 14 Hz), 4,50 (1H, d, J = 14 Hz), 4,79 (1H, d, J = 14 Hz), of 5.92 (1H, tt, J = 2,8 Hz 53 Hz), 5,94 (1H, s), 6,79-to 6.88 (2H, m), 7,25 (2H, d, J = 10 Hz), 7,50 to 7.62 (1H, m), to 7.59 (1H, s), 7,87 (1H, s), to $ 7.91 (2H, d, J = 10 Hz), with 8.05 (1H, s).

[]2D0by 12,4o(C = 1.0, methanol)

Working example 59. 4-[(2S)-2-(2,4-Differenl)-2-hydroxy-3-(1H - 1,2,4-triazole-1-yl)propyl] -2-[4-(2,2,2-triptoreline)phenyl] -3(2H, 4H)- 1,2,4-triazole (compound 91), colorless powder. Yield 22%.

1H-NMR (CDCl3) : 4,14 (1H, d, J = 14 Hz), 4,24 (1H, d, J = 14 Hz), 4,35 (2H, q, J = 8 Hz), 4,51 (1H, d, J = 14 Hz), was 4.76 (1H, d, J = 14 Hz), of 6.02 (1H, s), 6,72-6,89 (2H, m), 6,97 (2H, d, J = 9,2 Hz), 7,51-7,63 (1H, m), at 7.55 (1H, s), 7,79 (2H, d, J = 9,2 Hz), 7,86 (1H, s), of 8.06 (1H, s).

Working example 60. 2-[(2R)-2-(2,4-Differenl)-2-hydroxy-3-(1H - 1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)- 1,2,4-triazole (compound 74), colorless powder. Yield 46%.

1H-NMR (CDCl3) : 4,18 (7,53 (1H, s), 7,56-to 7.64 (1H, m), to 7.84 (1H, s), 8,15 (1H, s).

Working example 61. 2-[(2R)-2-(2,4-Differenl)-2-hydroxy-3-(1H - 1,2,4-triazole-1-yl)propyl] -4-(4-trifloromethyl)-3(2H, 4H)-1,2,4-triazole (compound 70), colorless powder. Yield 41%.

1H-NMR (CDCl3) : 4,19 (1H, d, J = 15 Hz), 4,60 (1H, d, J = 15 Hz), 4.72 in (2H, s), 5,69 (1H, s), 6,76-to 6.88 (2H, m), 7,32 (2H, d, J = 9 Hz), 7,46-to 7.64 (1H, m), to 7.50 (2H, d, J = 9 Hz), to 7.59 (1H, s), to 7.84 (1H, s), 8,14 (1H, s).

Working examples 62-71. The following compounds were obtained in accordance with the method described in working example 2.

Working example 62. 1-1[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -3-[4-[4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] - 1-piperazinyl] phenyl] -2(1H, 3H)-imidazolone (compound 104), colorless powder. Yield 62%.

1H-NMR (CDCl3) : to 1.22 (3H, d, J = 7 Hz), 3,23-to 3.38 (8H, m), 4,22 (1H, d, J = 15 Hz), or 4.31 (2H, t, J = 12 Hz), to 4.92 (1H, q, J = 7 Hz), 5,10 (1H, d, J = 15 Hz), between 6.08 (1H, tt, J = 53, 5 Hz), 6,59 (1H, d, J = 3,0 Hz), of 6.68 (1H, d, J = 3,0 Hz), 6.73 x-7,06 (8H, m), 7,43-rate of 7.54 (3H, m), 7,72 (1H, s), 7,89 (1H, s).

Working example 63. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-[4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl] - 1-piperazinil]phenyl]-3(2H,4H)-1,2,4-triazole (compound 105), colorless powder. Yield 54%.

1H-NMR (CDCl3) : of 1.29 (3H, d, J = 7,0 Hz), 3,23-of 3.42 (8H, m), or 4.31 (2H, t, J = 12 Hz), 4,35 (1H, d, J = 15 Hz), 5,02 s), of 7.96 (1H, s).

Working example 64. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,2-triptoreline)phenyl]-5(1H,4H)- 1,2,4-triazole (compound 106), colorless powder. The output is 27%.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7 Hz), 4,35 (1H, d, J = 16 Hz), to 4.41 (2H, q, J = 8 Hz), to 5.08 (1H, d, J = 16 Hz), 5,10 (1H, q, J = 7 Hz), the 5.51 (1H, s), 6.75 in-to 6.88 (2H, m), to 7.09 (2H, d, J = 9 Hz), 7,51-7,63 (1H, m), 7,72 (1H, s), of 7.90 (2H, d, J = 9 Hz), to $ 7.91 (1H, s).

Working example 65. 1-[1(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl]-4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]- 5(1H, 4H)-1,2,4-triazole (compound 107), colorless powder. Yield 48%.

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7,2 Hz), 4,34 (1H, d, J = 14,4 Hz), to 5.08 (1H, d, J = 14,4 Hz), 5,10 (1H, q, J = 7,2 Hz), of 5.50 (1H, s), 5,95 (1H, tt, J = 52,8, 2,8 Hz), 6.73 x-6,91 (2H, m), 7,38 (2H, d, J = 9 Hz), 7,49-to 7.64 (1H, m), 7,72 (1H, s), to $ 7.91 (1H, s), 8,01 (2H, d, J = 9 Hz).

IRKBrmaxcm-1: 3400, 3080, 1730, 1618, 1514, 1502, 1387.

Working example 66. 1-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,3,3,3-pentafluoropropane)phenyl] - 5(1H,4H)-1,2,4-triazole (compound 108), colorless powder. Yield 53%.

1H-NMR (CDCl3) : of 1.45 (3H, d, J = 7,2 Hz), 4,35 (1H, d, J = 14,2 Hz), 4,47 (2H, dt, J = 12,2, 1 Hz), to 5.08 (1H, d,J = 14,2 Hz), 5,10 (1H, q, J = 7,2 Hz), of 5.50 (1H, s), 6,74-of 6.90 (2H, m), to 7.09 (2H, d, J = 9,2 Hz), 7,49-the 7.65 (1H, m), 7,72 (1H, s), of 7.90 (2H, d, J = 9,2 Hz), to $ 7.91 (1H, s).

IRKBr

1H-NMR (CDCl3) : of 1.46 (3H, d, J = 7,2 Hz), 4,35 (1H, d, J = 14,4 Hz), a 4.53 (2H, t, J = 13 Hz), to 5.08 (1H, d, J = 14,4 Hz), 5,10 (1H, q, J = 7,2 Hz), 5,52 (1H, s), 6,11 (1H, tt, J = 52, of 5.4 Hz), 6,74-6,91 (2H, m), 7,10 (2H, d, J = 9,2 Hz), 7,50-7,66 (1H, m), 7,73 (1H, s), to $ 7.91 (2H, d, J = 9,2 Hz), 7,92 (1H, s).

IRKBrmaxcm-1; 3400, 3080, 1722, 1618, 1599, 1516, 1459.

Working example 68. 2-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -5-methyl-4-[4-(2,2,3,3 - tetrafluoropropoxy)phenyl] -3(2H, 4H)-l, 2,4-triazole (compound 110), colorless powder. Yield 44%.

1H-NMR (CDCl3) : a 1.25 (3H, d, J = 7 Hz), 2,19 (3H, s), and 4.40 (1H, d, J = 14,8 Hz), 4,42 (2H, t, J = and 11.8 Hz), equal to 4.97 (1H, d, J = 14,8 Hz), is 5.06 (1H, q, J = 7 Hz), 5,62 (1H,s), between 6.08 (1H, tt, J = 53,2 Hz, J = 4,6 Hz), 6,84-of 6.90 (2H, m), to 7.09 (2H, dt, J = 9 Hz, 2,6 Hz), 7,33 (2H, dt, J = 9 Hz, 2,6 Hz), 7,50-the 7.65 (1H, m), of 7.70 (1H, s), 7,98 (1H, s).

Working example 69. 2- [(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3(1H-1,2,4-triazole-1-yl)propyl]-5-methyl-4-[4-(1,1,2,2-tetrafluoroethoxy)phenyl] - 3(2H,4H)-1,2,4-triazole (compound 111), colorless powder. Yield 46%.

1H-NMR (CDCl3) : of 1.26 (3H, d, J = 7 Hz), 2,24 (3H, s), 4,42 (1H, d, J = 14,6 Hz), to 4.98 (1H, d, J = 14,6 Hz), 5,07 (1H, q, J = 7 Hz), of 5.55 (1H, s), 5 96 (1H, tt, J = 53,2 Hz and 2.8 Hz), 6.75 in-6,90 (2H, m), 7,41 (4H, s), 7,50-the 7.65 (1H, m), 7,71 (1H, s), of 7.97 (1H, s).

Working example 70. 2-(4-Chlorophenyl)-4-[(1R,3R)-2-(2,4-differenl)- 2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -5-methyl-3(2H,4H)- 1,2,4-triaz = 7 Hz), of 2.38 (3H, s), 4,49 (1H, d, J = 14,2 Hz), 4,76-of 4.90 (1H, m), 4,89 (1H, d, J = 14,2 Hz), 6,23 (1H, br), 6,88-to 6.95 (1H, m), 6,99-7,07 (1H, m), 7,46-rate of 7.54 (1H, m), 7,46 (2H, d, J = 9 Hz), 7,55 (1H, s), of 7.90 (2H, d, J = 9 Hz), 8,14 (1H, s).

IRKBrmaxcm-1: 1712, 1702, 1680, 1650, 1619, 1502.

Working example 71. 4-[(1R,2R)-2-(2,4-Differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -5-methyl-2-(4-trifloromethyl)- 3(2H, 4H)-tetrazole (compound 113), colorless powder. Yield 72%.

IRKBrmaxcm-1: 1700, 1678, 1610, 1508, 1256, 1220.

Working example 72. K a mixture of 60% (w/w) of sodium hydride in oil (10 mg) and dimethylformamide (2 ml) is added 4-(4-triptoreline)-3(2H, 4H)-1,2,4-triazole (59 mg) at 0oC. the resulting mixture was stirred at room temperature for 10 minutes To a mixture of (2R,2S)-2-(2,4-differenl)-3-methyl-2-[(1H-1,2,4-triazole - 1-yl)methyl] oxirane (63 mg). After stirring for 19 h at 70oC the mixture was diluted with water (4 ml) and extracted with ethyl acetate (4 ml x 2). The extract is washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified using chromatography on silica gel (eluent - ethyl acetate: hexane = 3:1 to ethyl acetate) to obtain 1-[(1R, 2R)-2-(2,4-difterences)-2-hydroxy-1-methyl-3-(1H - 1,2,4-triaz the x2">

Working example 73. By the same method as in working example 72, (2R,2S)-2-(2,4-differenl)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)methyl-oxirane (63 mg) is subjected to reaction with 2-(4-triptoreline)-3(2H,4H)- 1,2,4-triazolone (59 mg) to give 4-[(1R,2R)-2-(2,4-differenl)- 2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -2-(4-triptoreline)- 3(2H,4H)-1,2,4-triazolone (compound 11) as a white powder (12 mg).

Working example 74. By the same method as in working example 72, (2R,3S)-2-(2,4-differenl)-3-methoxy-2-[(1H-1,2,4-triazole-1-yl)methyl] -oxirane (251 mg) is subjected to reaction with 2-(4-forfinal)-3(2H,4H)-1,2,4-triazolone (358 mg) to give 4-[(1R, 2R)-2-(2,4-differenl)-2-hydroxy-1-methyl - 3-(1H-1,2,4-triazole-1-yl)propyl] -2-(4-forfinal)-3(2H, 4H)-1,2,4-triazolone (compound 15) as a white powder (76 mg).

Working example 75. By the same method as in working example 72, (2R,3S)-2-(2,4-differenl)-3-methyl-2-[(1H-1,2,4-triazole-1-yl)methyl] -oxirane (251 mg) is subjected to reaction with 2-(4-chlorophenyl)-3(2H,4H)-1,2,4-triazolone (392 mg) to obtain 2-(4-chlorophenyl)-4-[(1R,2R)-2-(2,4-differenl)- 2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl]-3(2H,4H)-1,2,4-triazolone (compound 35) as colourless prisms (48 mg).

A preferred group of compounds expressed by the compound of General formula I according to the invention, proillyustrirovana 1.

Using the connection 30 obtained in working example 27, mix the following components. The mixture is Packed into gelatin capsules to obtain capsules, each of which contains a compound 30 of 50 mg.

Compound 30 (obtained in working example 27) 50 mg

Lactose 100 mg

Corn starch 40 mg

Magnesium stearate 10 mg

Only 200 mg

Preparation 2.

The connection 35, obtained in working example 32, and magnesium stearate granularit in the solution of the soluble starch. The resulting product is dried and then mixed with lactose and corn starch. The mixture is subjected to pressing to obtain tablets containing these components.

Compound 35 (obtained in working example 32, 50 mg

Lactose - 65 mg

Corn starch 30 mg

Soluble starch - 35 mg

Magnesium stearate 20 mg

Only 200 mg

Evaluation of antifungal activity of the compounds of formula I were conducted by the following method: a sheet of filter paper (manufactured by Toyo Seisakusho, 8 mm in diameter) soaked in 1000 mg/ml solution of the compounds of formula I in methanol was placed on an agar plate containing various fungi were incubated at 28oC in those who esewani the following culture medium:

A: nitrogen is the main yeast agar medium (pH 7.0)

B: peptone-yeast extract-glucose agar medium (pH 7.0).

Antifungal activity of the compounds of formula I are shown in table. 28.

Antifungicide activity of the compounds of formula I against Candida albicans are shown in table. 29-32.

The protective properties of the compounds of formula I against Candida albicans infection shown in mice and are shown in table. 33 and 34.

Research method: five-week mouse Crj: CDF1were inoculated with the minimum lethal dose of Candida albicans intravenously. The investigated compound was administered orally one time, immediately after infection. Activity is expressed in units of the ED50calculated by the method of Reed and Muench for the degree of survival after 7 days after infection.

1. Derived Azola formula I

< / BR>
where Ar - disubstituted by halogen phenyl group;

R1is hydrogen atom or lower alkyl group;

R3- lower alkyl, possibly substituted by halogen, phenyl, unsubstituted or substituted lower alkyl, halogen, trifluoromethyl, lower alkoxy, halogen (lower) alkoxy, piperazinil, benzylpiperazine, lower arylpiperazines, lower alkoxypiperidine, alkyl the group;

Y and Z, independently, is a nitrogen atom or a methine group which optionally may be additionally substituted lower alkyl group,

or kislotoupornye salt.

2. The compound or its salt under item 1, where X is the nitrogen atom.

3. The compound or its salt under item 1, where R1is methyl.

4. The compound or its salt under item 1, where Ar is 2,4-diferencia group.

5. The compound or its salt under item 1, where R3is phenyl, unsubstituted or substituted lower alkyl, halogen, trifluoromethyl, lower alkoxy, halogen(lower)-alkoxy, piperazinil, benzylpiperazine, lower arylpiperazines, lower alkoxypiperidine, the alkyl portion of which may be substituted with halogen.

6. The compound or its salt under item 1, where R3- substituted phenyl group.

7. The compound or its salt according to p. 6, where R3is a phenyl group which is substituted by a halogen atom.

8. The compound or its salt according to p. 6, where R3is a phenyl group which is substituted triptorelin group.

9. The compound or its salt according to p. 6, where R3is a phenyl group substituted by halogen(lower)alkoxy group.

10. The compound or its salt according to p. 7, where R3the Association or its salt under item 9, where R3- 4-trifloromethyl.

13. The compound or its salt under item 9, where R3- 4-(2,2,2-triptoreline)phenyl.

14. The compound or its salt under item 9, where R3- 4-(2,2,3,3-tetrafluoropropoxy)phenyl.

15. The compound or its salt under item 9, where R3- 4-(1,1,2,2-tetrafluoroethoxy)phenyl.

16. The compound or its salt under item 9, where R3- 4-(2,2,3,3,3-pentafluoropropane)phenyl.

17. The compound or its salt under item 1, where Y and Z, independently, is a hydrogen atom or a methine group which may be optionally substituted methyl group.

18. The compound or its salt under item 1, where any one of Y and Z is nitrogen atom and the other methine group.

19. Connection on p. 1 representing 2-[(1R,2R)-2-(2,4-differenl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -4-(4-trifloromethyl)-3-(2H,4H)-1,2,4-triazole or its salt.

20. Connection on p. 1 representing 2-[(1R,2R)-2-(2,4-differenl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazole or its salt.

21. Connection on p. 1 representing 2-[(1R,2R)-2-(2,4-differenl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -4-[1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2-4-triazole or all-1-yl)propyl] -2-(4-trifloromethyl)-3(2H,4H)-1,2,4-tetrazole or its salt.

23. Connection on p. 1 representing 2-[(1R,2R)-2-(2,4-differenl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,2-triptoreline)phenyl]-3(2H,4H)-1,2-4-triazole or its salt.

24. Connection on p. 1, representing 4-[(1R,2R)-2-(2,4-differenl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-(2,2,2-triptoreline)phenyl]-3(2H,4H)-1,2,-4-triazole or its salt.

25. Connection on p. 1, representing 4-[(1R,2R)-2-(2,4-differenl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -2-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-3(2H,4H)-1,2,4-triazole or its salt.

26. Connection on p. 1 representing 2-[(1R,2R)-2-(2,4-differenl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazole-1-yl)propyl] -4-[4-[4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl-1-piperazinil] phenyl] -3-(2H,4H)-1,2,4-triazole or its salt.

27. The method of obtaining the compounds of formula I or its salts under item 1, characterized in that carry out the reaction of the compound represented by formula II:

< / BR>
where values radicals are the same as specified for formula I,

with the compound represented by formula III

< / BR>
where values radicals are the same as specified for formula I,

or its salt.

28. The method of obtaining the compounds of formula I or its salts under item 1, characterized in that h is indicated for the formula I,

or its salt with a compound represented by the formula V

< / BR>
where values radicals are the same as specified for formula I,

or its salt.

29. The pharmaceutical composition exhibiting antifungal activity, containing as active compounds derived azole, and a pharmaceutically acceptable carrier, excipient or diluent, wherein as derived azole contains an effective amount of the compounds represented by formula I, as defined in paragraph 1, or its pharmaceutically acceptable salt.

 

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,

in which n is an integer from 1 to 5; each of R1and R2which may be identical or different, is hydrogen, halogen, -CN, -NO2C1-C4the alkyl, or a group:, R3is hydrogen, halogen, -CN or-NO2

The invention relates to the field of synthesis of new biologically active compounds

Tetrathiotetracene // 2068846
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- aminoacyl)-5,10-dihydro-11h-dibenzo[b, e] [1,4]- diazepin-11-ons or their salts, possess antiarrhythmic activity" target="_blank">

The invention relates to the field of chemistry, particularly to the new series of compounds - 5-(-aminoacyl)-5,10-dihydro-11N - dibenzo [b,e]-[1,4]-diazepin-11-Onam General formula

where R1is a hydrogen atom or chlorine;

R2is a hydrogen atom or a C1-C2-alkyl;

R3- C1-C2-alkyl or cyclohexyl, or R2and R3together with the nitrogen atom can be morpholinyl or N-methylpiperazine balance; provided that, if R2is a hydrogen atom, R3can be1-C3-alkyl or cyclohexyl,

n=3-6;

m = 0-1; X=Cl or Br

The invention relates to heterocyclic amines of formula I:

,

in which

X represents-CH2-group or-S-group;

B denotes a group selected from a number containing-CO -, - CH2OCO-, -CH2OCS-, -CH2NHCO - CH2NHCS-group;

D represents benzhydryl or phenyl group, optionally substituted by halogen atoms, and heterocyclic group, selected from a number containing 1,3,5-triazine-2-yl, pyridin-2-yl and pyrimidine-4-yl, and optionally substituted by one or two substituents selected from the group comprising amino, mono - or di-(C1C6) alkylamino, mono- (C3-C7)-alkynylamino, mono-(C3-C7)-quinil-amino group and pyrrolidin-1-yl group;

The is a simple carbon-carbon bond or a group of the formula: -CH2CH2or CRaRb-, where Raand Rbis a hydrogen atom, (C1-C3)alkyl, or taken together with the carbon atom to which they are attached, form a (C3-C6) cycloalkyl;

A is selected from the group comprising (a) carboxyl group optionally esterified (C1-C4) Ukrspirt the crystals: -C–ěNHRgOH, where Rcand Rdidentical or different, represent a hydrogen atom, (C1-C6) alkyl, benzyl, pyridin-2-yl, or taken together with the nitrogen atom to which they are bound, form piperidino, morpholino-, 4-thiomorpholine-, 4,5-diazepino, 4-(C1-C4)alkylpiperazine; Rfis a tolyl; Rgis a (C1-C4) alkyl;

(b) (C1-C3) alkyl;

(c) the group-NRcRdwhere Rcand Rddefined above,

(d) a cyano, if "y" does not mean a simple carbon-carbon bond

in the form of S-enantiomers, diastereomers, in the form of various racemic mixtures and their salts with pharmaceutically acceptable acids and bases
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