Derivatives of thiazolidine, the pharmaceutical composition having hypoglycemic and gipolipidemicescoy activity and activity inhibition alsoreported, and a method for the treatment and prevention of diseases of mammals

 

(57) Abstract:

Usage: in medicine. The proposed derivatives of thiazolidine formula I, where R1and R2- same or different and each represents hydrogen, alkyl with 1 to 8 carbon atoms, R3is hydrogen, a and b are the same or different and each represents hydrogen or alkyl of 1 to 8 carbon atoms, or a - b groups: -C=O =C=S, -CH2CH2-, X - band W-(CH2)m-X'-, where W is phenyl, unsubstituted or substituted by at least one Deputy, selected from alkyl with 1 to 4 carbon atoms, alkoxy groups with 1 to 4 carbon atoms, halogen, phenyl, and groups-NRandRinwhere Randand Rin- same or different and each represents hydrogen or alkyl with 1 to 8 carbon atoms, X' is a single bond, oxygen, sulphur or the group NR4where R4is alkyl with 1 to 8 carbon atoms, m = 0 to 8, Y is a group of the formula -(CH2)n-Y'-, in which Y' is oxygen, sulphur; n = 1 to 5; Z is a group of formula II and their salts. The proposed pharmaceutical composition comprising a compound of formula I. a method for treatment and prevention of diseases of mammals, being treated with compounds having hypoglycemic and gipolipidemicescoy activity. Join izaberete is 2">

The present invention relates to a series of compounds, which may be regarded as derivatives of thiazolidine and oxazolidine. The present invention also relates to methods and compositions using these compounds, and to methods of producing these compounds.

Compounds belonging to this broad class of compounds disclosed in the publications Europatent NN 008203, 139421, 441605, 208420, 528734, 177353, 306208 and 356214, as well as in WO 92/07850, 92/07839, 91/07107, 92/02520 and 92/03425.

Brief description of the invention.

The aim of the present invention to provide a series of new chemical compounds, which may be regarded as derivatives of thiazolidine and oxazolidine or their derivatives with an open ring.

Another and more specific objective of the present invention to provide such compounds or at least some of them, which can be used for the treatment and/or prevention of one or more diseases such as hyperlipemia, hyperglycemia, inadequate glucose tolerance, insulin resistance and diabetic complications.

Other objectives and advantages of the present invention will be clear from the following is where

R1and R2may be the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms;

R3represent a hydrogen atom;

A and B may be the same or different and each represents a hydrogen atom; alkyl group having 1-8 carbon atoms;

A and B, taken together, represent a group of formula:

X represents a group of formula W-(CH2)m-X1- where W represents a phenyl group which is unsubstituted or substituted by at least one Deputy, selected from alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, halogen atoms, phenyl groups, and groups of formula-NRaRbin which Raand Rbare the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms;

X1represents a single bond, an oxygen atom, a sulfur atom, a group of the formula in which R4represents an alkyl group having from 1 to 8 carbon atoms;

and

m represents 0 or an integer from 1 to 8

Y represents a group of the formula: -(CH2)n-Y1,
to 5;

Z represents a group of the formula (I):

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in which

R5represents a hydrogen atom

and, in addition, the present invention relates to salts of the abovementioned compounds of the formula (I).

The present invention also relates to pharmaceutical compositions intended for the treatment or prevention of diabetes or hyperlipemia and containing an effective amount of the active compound in combination with a pharmaceutically acceptable carrier or diluent and a specified active compound is chosen from the group comprising the compounds of formula (I) defined above, and their salts.

In addition, the present invention relates to a method of treatment or prevention of diabetes or hyperlipemia in mammals, including humans, consists in the fact that the specified mammal is administered an effective amount of an active compound selected from the group comprising the compounds of formula (I) defined above, and their salts.

The present invention also relates to methods of preparing compounds of the present invention, described in more detail below.

Detailed description of the invention

In the compounds of the present invention the alkyl groups are presented in carbon; as examples of alkyl groups can serve as methyl, ethyl, sawn, ISO-propyl, bucilina, isobutylene, second-bucilina, tert-bucilina, pentilla, 2-pencilina, 3-pencilina, 2-methylbutyl, 3-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropylene, 2,2-dimethylpropylene, hexeline, 2-exilda, 3-exilda, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2, -dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-trimethylethylene, 1,2,2-trimethylpropyl, heptylene, 2-heptylene, 3-heptylene, 4-heptylene, 3,3-dimethylpentyl, anjilina, 1-methylheptane, 2-ethylhexyl and 1,1,3,3-TETRAMETHYLBUTYL group. Of them, preferred are straight or branched alkyl group having 1-6 carbon atoms, and most preferred are methyl and ethyl groups.

If each of A and/or B, which may be the same or different, represents an alkyl group, this group may be a straight or branched alkyl group having 1-8 carbon atoms, and similar alkyl groups, examples of which are given above in relation to the present invention can be converted into salts with bases and using standard techniques. Examples of such salts include: salts of alkali metals such as sodium, potassium or lithium; salts of alkaline-earth metals such as barium or calcium; salts of other metals, such as magnesium or aluminum; ammonium salts, salts of organic bases such as methylamine, dimethylamine, triethylamine, Diisopropylamine, cyclohexylamine or dicyclohexylamine; and salts formed in basic amino acids such as lysine or arginine. While preferred are pharmaceutically acceptable salts.

The compounds of formula (I) of the present invention may exist in the form of various isomers. As shown, for example, in the formula (Ia):

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(where R1, R2, R3, A, B, X, Y, and Z are defined above), the carbon atom denoted by*1, is always asymmetric carbon atom; and the carbon atom denoted by *2 is asymmetric atom in the case when R1and R2represent different groups.

In addition, if Z represents a group of formula (Ia):

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(where R5defined above), the carbon atom denoted by *3, is also asymmetric carbon atom.

Although in the present description all isomers represented by one m is, the rich in these mixtures of isomers may be present in any ratio. If the technique used is stereospecific synthesis or as starting materials are optically active compounds, can be obtained directly individual isomers; and on the other hand, if the quality of the final product is obtained mixture of isomers, the individual isomers can be obtained using conventional separation technique.

In addition, if Z represents a group of the formula (i):

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and R5represents a hydrogen atom, the compounds can form tautomers shown in the following diagram:

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In the above formula (I) all tautomers and mixtures of equivalent mass or unequal masses of these tautomers represented by a single formula. Therefore, it should be noted that all of these isomers and mixtures of these isomers are included in the scope of the present invention.

Moreover, the present invention also includes all of the solvate (e.g., hydrates) of compounds of formula (I), their salts.

More preferred compounds of the present invention are those compounds of formula (I), their salts, in which:

2) R1and R2MOU carbon;

R3represents a hydrogen atom;

A and B are the same or different and each represents a hydrogen atom, methyl, ethyl, through either A and B taken together form a group of the formula: or-CH2CH2- ;

X represents a group of the formula W-(CH2)m-X1- where W represents a phenyl group which is unsubstituted or substituted by 1-3 substituents selected from alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, halogen atoms, phenyl groups and groups of formula-NRaRbin which Raand Rbare the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms,

X1represents a simple bond, an oxygen atom, a sulfur atom or a group of formula-N (R4), where R4is methyl, ethyl or through the group;

m is zero or an integer from 1 to 6;

Y represents a group of formula -(CH2)n-Y' where Y' is an oxygen atom or sulfur, and n is an integer from 1 to 5;

Z represents a group of formula (Vii):

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Even more preferred compounds of the present invention ablauts is for one of them represents a hydrogen atom, and the other is an alkyl group having 1-4 carbon atoms;

R3represents a hydrogen atom,

A and B are the same or different and each represents a hydrogen atom, a methyl, an ethyl group; or A and B taken together form a group of the formula or-CH2CH2-;

X represents a group of the formula W -(CH2)m-X1- where W represents a phenyl group which is unsubstituted or substituted by 1-3 substituents selected from the group comprising: halogen atom, methyl, ethyl, phenyl, amino, dimethylamino, methoxy and ethoxy-group;

X1- represents a simple bond, an oxygen atom, a sulfur atom or a group of formula-N(Me)-;

m is zero or an integer from 1 to 6;

Y represents a group of formula -(CH2)n- Y'-, where Y' represents an oxygen atom or a sulfur atom and n is an integer from 1 to 3;

and

Z represents a group of formula (Vii):

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Even more preferred compounds of the present invention are those compounds of formula (I), their salts, in which:

4) R' and R2both represent hydrogen atoms or one represents a hydrogen atom and the other represents methyl, ethyl, sawn or Afleet a hydrogen atom or methyl, ethyl group; or A and B taken together form a group of the formula or

X represents a group of the formula W-(CH2)m-X1where W represents a halogen-substituted phenyl, phenylphenyl, metoksifenilny or phenyl group, X1represents an oxygen atom or a sulfur atom, m is zero or an integer from 1 to 6;

Y represents a group of formula-CH2O or -(CH2)2O-;

and

Z represents a group of formula (Vii):

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The most preferred compounds of the present invention are those compounds of formula (I), their salts, in which:

5) R1and R2both represent hydrogen atoms or one represents a hydrogen atom and the other represents a methyl or ethyl group;

R3represents a hydrogen atom;

A represents a hydrogen atom, and B represents a hydrogen atom or a methyl group; or A and B taken together form a group of the formula or

X represents a group of the formula W-(CH2)m-O-, where W represents phenyl, 3-chloraniline, 4-chloraniline, 3-metoksifenilny, 4-metoksifenilny or 4-phenylphenyl group; and m is zero or an integer from 1 to 6;

Y represents a group of formula-CH2
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In the above formulae the substituents are as defined in tables 1-7, respectively, that is, table 1 relates to formula (I-1), table 2 relates to formula (1-2), etc. to table 7, which refers to the formula (1-7). In these tables have been following notation is used:

Ac - acetyl

Boz - benzoyl

Bu - butyl

iBu is isobutyl

tBu is t-butyl

Bz - benzyl

Car - carbarnoyl

Et - ethyl

Etc - etoxycarbonyl

Hp - heptyl

Hx - hexyl

Me - methyl

Mec - methoxycarbonyl

Oc - octyl

Ph - phenyl

Piv - pivaloyl

Pn - pencil

Pr - propyl

iPr is isopropyl

Prn - propionyl

Pyr - pyridyl

In table 7 the position of the substituents R3and Z with respect to Y is indicated in brackets after the identification of the Deputy.

Of the above compounds, preferred are compounds NN 1-2, 1-4, 1-48, 1-49, 1-51, 1-64, 1-69, 1-79, 1-91, 1-92, 1-93, 1-94, 1-95, 1-128, 1-158, 1-159, 1-160, 1-161, 1-162, 1-163, 1-164, 1-165, 1-166, 1-167, 1-168, 1-169, 1-170, 1-171, 1-173, 1-176, 1-177, 1-179, 1-180, 1-181, 1-184, 1-186, 1-187, 1-188, 1-189, 1-190, 1-191, 1-192, 1-193, 1-195, 1-197, 1-200, 1-201, 1-204, 1-205, 1-206, 1-207, 1-208 and 1-209, of which more preferred are compounds NN 1-2, 1-4, 1-51, 1-64, 1-69, 1-79, 1-91, 1-93, 1-94, 1-95�E. preferred are compounds NN 1-2, 1-4, 1-64, 1-91, 1-93, 1-94, 1-95, 1-159, 1-161, 1-162, 1-164, 1-173, 1-179, 1-186, 1-191, 1-193, 1-195, 1-205 and 1-206.

The most preferred compounds are the following compounds NN:

1-2. 5-(4-{3-phenyl-2-hydroxypropylamino)propoxy]benzyl}- thiazolidine-2,4-dione;

1-93. 5-{ 4-[2-(5-3'-chlorphenoxamine-2-oxo-oxazolidin-3-yl) ethoxy] benzyl}thiazolidine-2,4-dione;

1-94. 5-{4-[2-(5-3'-chlorphenoxamine-2-oxo-oxazolidin-3-yl) propoxy] benzyl}thiazolidine-2,4-dione;

1-95. 5-{ 4-[2-(5-3'-chlorphenoxamine-2-thioxo-oxazolidin-3-yl) propoxy]benzyl}thiazolidine-2,4-dione;

1-162. 5-{ 4-[2-(3-6'-phenylhexane-2-hydroxypropyl-amino) propoxy] benzyl}thiazolidine-2,4-dione; and

1-191. 5-{4-[2-(5-3'-chlorphenoxamine-2-oxo-oxazolidin-3-yl)- butoxy] benzyl} thiazolidine-2,4-dione, of which particularly preferred are compounds NN 1-2, 1-94 and 1-95.

Compounds of the present invention can be obtained in various ways, which are typically used by professionals to produce compounds of this type. For example, these compounds can be obtained in accordance with Reaction schemes A, B, C, and F.

Reaction scheme A.

Below is a General scheme that can be used for any connection of this izaberete A , B and Z are as defined above.

Stage A1

In Stage A1 is a compound of the formula (R-3) are obtained by reaction of amerosport formula (R-1) with the compound of the formula (R-2). Compound (R-2) is a known compound and can be obtained by known methods, for example by reaction of halogenation and phenolic compounds described in the prior publication of the Japan patent (Kokai) N Hei-6-25118.

Reaction Stage A1 can be carried out in the absence or presence of a dehydrating reagent, such as coal anhydride alkali metals, such as anhydrous potassium carbonate or anhydrous potassium carbonate, sulphuric anhydride alkali metals, such as anhydrous sodium sulfate; the acid chloride of alkaline-earth metals, such as anhydrous calcium chloride; sulfuric anhydride alkali-earth metals, such as anhydrous magnesium sulfate or molecular sieves.

The above reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent, provided that it has no adverse effect on the reaction or it uses the reagents, and provided that specified. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane, heptane; halogenated hydrocarbons such as chloroform, methylene chloride and carbon tetrachloride; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; alcohols such as methanol and ethanol; sulfoxidov, such as dimethylsulfoxide or sulfolane; or mixtures of any two or more of these solvents.

This reaction can be carried out in a wide temperature range, and the exact value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be conducted at a temperature of cooling with ice until the temperature of the distillation of the solvent. The time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents and solvent. However, when carrying out the reaction in the above preferred conditions, the period of time from 0.5 h to 10 h is mostly sufficient.

This reaction of predominate in the range of temperature cooling with ice to a temperature of distillation of the solvent. And more preferably, if the reaction is carried out in benzene for 1-3 hours under the conditions of heating under reflux for the reaction of dehydration.

Stage A2

In Stage A2, the compound of formula (R-4) obtained by recovery of the compounds of formula (R-3).

This reaction is usually carried out by hydrogenation in the presence of a reducing agent or in the presence of a catalyst.

If the compound of the formula (R-3) is subjected to hydrogenation in the presence of a reducing agent, such agent may be, for example, a metal hydride, such as lithium borohydride, sodium borohydride, cyanoborohydride sodium, alumoweld lithium or hydride Diisopropylamine.

The above reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it does not exert undesirable influence on the reaction or on the underlying reagents, and provided that the solvent is capable of dissolving at least to a certain extent, involved in the reaction reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xilinguole, dimethylacetamide and triamide hexamethylphosphoric acid; alcohols such as methanol, ethanol and isopropanol; or a mixture of two or more of these solvents.

This reaction can be carried out in a wide range of temperatures and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be carried out in the temperature range from temperature cooling with ice to a temperature of heating, for example, using a reverse refrigerator. The time required for the reaction may also be widely variable depending on many factors, namely, the reaction temperature and the nature of the reagents and solvent. However, when carrying out the reaction in the above preferred conditions, the period of time from 0.5 h to several days is generally sufficient.

This reaction preferably takes place in an alcohol solvent in the presence of sodium borohydride or laborgerate sodium during the period from 1 hour to 1 day, in conditions of cooling with ice or at a temperature in the range of temperature cooling with ice up to 50oC.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose can be used, in principle, any solvent provided that it has no undesirable effect on the reaction or on the underlying reagents, and capable of dissolving at least to a certain extent, these reagents. Examples of suitable solvents are ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide and dimethylacetamide; alcohols such as methanol, ethanol and isopropanol; esters of organic acids, such as methyl acetate and ethyl acetate; or a mixture of two or more of these solvents.

Stage A3

In Stage A3 compound of the formula (R-5) are obtained by alkylation, aralkylamines, acylation or carbamylcholine the compounds of formula (R-4).

Alkylation reaction and aralkylamines usually carried out by reaction of compounds of formula (R-4) with alkylhalogenide or aralkylamines or alkilany or aralkylated complex air alkanesulphonic acid or arylsulfonic acid (for example, with melancolico acid.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent, provided that it has no undesirable effect on the reaction or on the underlying reagents and capable of dissolving at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; sulfoxidov, such as dimethyl sulfoxide; halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane; sulfolan, such as methylene chloride, chloroform and 1,2-dichloroethane; sulfolane; or mixtures of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be carried out in the temperature range from temperature cooling with ice to a temperature of distillation of the solvent. Time trabeation temperature and the nature of the reagents and solvent. However, when carrying out the reaction in the above preferred conditions, the period of time from 0.5 h to several days is usually sufficient.

The acylation reaction is usually carried out in the absence or in the presence of an acid acceptor. Suitable allerease agents are acylhomoserine and acid anhydrides.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it has no undesirable effect on the reaction or on the underlying reagents and capable of dissolving at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; sulfoxidov, such as dimethyl sulfoxide; halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane; sulfolane; or mixtures of any two or more of these solvents.

This reaction may proceed in a wide range but usually, this reaction can be carried out in the temperature range starting from temperature cooling with ice to a temperature of distillation of the solvent. The time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents and solvent. However, when carrying out the reaction in the above preferred conditions, the period of time from 0.5 h to several days is usually sufficient.

If A and B taken together represent a group, as > C=0, > C=S, as the reaction agent is used preferably carbonyloxy agent (for example, phosgene, diphosgene, triphosgene, carbonyldiimidazole or an ester of Harborview acid, such as ethylchloride); thiocarbanilide agent (for example, thiophosgene or thiocarbonyldiimidazole), oxalicacid, helodermatid (for example, chlorocatechol or bromoacetamide), sulfurylchloride or haloalkaliphilic (for example, chloromethanesulfonyl).

This reaction is usually carried out in the absence or in the presence of an acid acceptor. If the reaction is carried out in the presence of an acid acceptor, such acid acceptor may be, for example, organic osenat sodium, sodium bicarbonate, potassium carbonate or potassium bicarbonate.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent, provided that it has no undesirable effect on the reaction or on the underlying reagents and capable of dissolving at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; halogenated hydrocarbons such as chloroform, methylene chloride, 1,2-dichloroethane and carbon tetrachloride; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; urea such as N,N'-dimethylimidazolidine; sulfoxidov, such as dimethyl sulfoxide; NITRILES such as acetonitrile and propionitrile; sulfolane; or mixtures of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be carried out in di is more preferably at a temperature of cooling with ice or at a temperature in the range from the specified temperature cooling with ice up to 50oC. the Time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, the period of time from 0.5 to 50 hours, and more preferably from 5 to 50 hours, is sufficient.

The reaction scheme B.

This scheme provides several ways to obtain the characteristic compounds of the present invention using the same source materials that were used in the Reaction scheme A.

The reaction scheme B1:

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The reaction scheme B2:

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The reaction scheme B3:

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In the above formulas, X, A, B, R1, R2and Z are defined above;

R is a straight or branched lower alkyl group having preferably 1 to 6 carbon atoms, and more preferably 1 to 4 carbon atoms, for example, one of the groups illustrated above for R1and in particular, a methyl or ethyl group;

Y2represents an oxygen atom or a sulfur atom;

"Halo" means a halogen atom such as chlorine atom, bromine atom or iodine atom; and

Z1represents the group and BI compound of the formula (R - 6) are obtained by alkylation, aralkylamines, acylation or carbamylcholine the compounds of formula (R - I). This reaction is carried out generally in accordance with the procedure described in Stage A3 of the Reaction scheme A, using the same reaction conditions and the same reagents.

Stage B2

In Stage B2 compound of the formula (R - 8) are obtained by reaction of compounds of formula (R - 6) with the compound of the formula (R - 7) in the presence or absence of a base. If B represents an acyl group or karbamoilnuyu group, it is preferred if the compound of the formula (R - 6) is first subjected to interaction with a base such as sodium hydride, and then the obtained compound is subjected to reaction with the compound of the formula (R - 7).

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it has no undesirable effect on the reaction or on the reagents and capable of dissolving at least to a certain extent, these reagents. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, the d hexamethylphosphoric acid; the sulfoxidov, such as dimethyl sulfoxide; halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane; sulfolane; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be carried out in the temperature range from temperature cooling with ice to a temperature of heating. The time required for the reaction, may;s widely vary depending on many factors, namely, the reaction temperature and the nature of the reagents and solvent. However, in many cases, the implementation of this reaction period of time from 0.5 h to several days is usually sufficient.

Stage B3

In Stage B3 compound of the formula (R - 9) is obtained by recovery of the compounds of formula (R - 8). In this reaction can be used, in principle, any reducing agent commonly used in reactions of this type. Examples of reducing agents are metal hydrides such as sodium borohydride, lithium borohydride, the t in the presence of a solvent. For this purpose, can be used any solvent provided that it has no undesirable effect on the reaction or on the reagents and capable of dissolving at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; alcohols such as methanol, ethanol and isopropanol; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be carried out in the temperature range from temperature cooling with ice to a temperature of heating. The time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is Eiselstein of lithium borohydride over a period of time from 1 h to 1 day at a temperature ranging from room temperature to the temperature of the distillation of the reaction mixture.

Stage B4

In Stage B4 compound of the formula (R - 11) are obtained by reaction of Mitsunobu (O. Mitsunobu, Synthesis, p. I (1981)), which is subjected to the compound of formula (R - 9) and the compound of formula (R - 10) with subsequent removal triphenylmethyl group.

The first stage of this reaction is normally and preferably carried out in the presence of a solvent. In this reaction may be used any solvent provided that it has no undesirable effect on the reaction or on the underlying reagents and capable of dissolving at least to a certain extent, these reagents. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; halogenated hydrocarbons such as chloroform, methylene chloride and carbon tetrachloride; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, this re heating, and more preferably at a temperature of cooling with ice, either in the temperature range from temperature cooling with ice up to 60oC. the Time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, the period of the reaction is from several hours to several days, and more preferably from 5 h to 3 days.

The second stage reaction is carried out by a reaction between the compounds with an acid, such as acetic acid, triperoxonane acid or hydrochloric acid, in the presence or in the absence of solvent; or by the reaction of catalytic hydrogenation of the compounds obtained in the presence of a solvent.

If this reaction is carried out by reaction of the obtained compound with an acid in the presence or in the absence of solvent, this reaction can be carried out in accordance with standard techniques (for example, J. W. Grcene, Protective Groups in Organic Synthesis, John Wiley & Sons; J. F. W. McOmie, Protective Groups in Organic Chemistry, Plenum Press).

If the resulting compound is subjected to reaction citator, commonly used in reactions of this type, such as palladium charcoal.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it has no undesirable effect on the reaction or on the reagents and has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, dioxane and tetrahydrofuran; alcohols such as methanol, ethanol and isopropanol; acids such as formic acid, acetic acid and propionic acid; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be carried out in the range from about room temperature to the heating temperature. Time, which requires that the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the implementation of this reaction is from several hours to several days, and more preferably from 1 h to 3 days.

The above reaction is usually carried out at atmospheric pressure or, preferably, at a pressure higher than atmospheric.

Stage B5

In Stage B5 compound of the formula (R - 12) are obtained by reaction of compounds of formula (R - 9) derived from 4-forventelige, such as 2-methoxy-4-forbindelse or 3-methyl-4-fermentology, in the presence of a base such as sodium hydride.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it has no undesirable effect on the reaction or on the underlying reagents and has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylacetamide, dimethylformamide and triamide to hexamethylphosphoramide in a wide range of temperatures, and the exact value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be carried out at a temperature in the range of temperature cooling with ice up to the heating temperature, and more preferably at a temperature of cooling or at a temperature in the range of temperature cooling with ice up to 60oC. the Time required for the reaction may also vary widely, depending on many factors, namely the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several hours to several days, preferably from 3 hours to 3 days.

Stage B6

In Stage B6 compound of the formula (R-13) are obtained by reaction of compounds of formula (R-12) with thiazolidine-2,4-dione.

This reaction can be carried out in the presence or in the absence of catalyst. If the reaction proceeds in the presence of a catalyst, examples of suitable catalysts can serve as sodium acetate, the acetate piperidine and benzoate piperidine.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any p and has the ability to dissolve, at least to a certain extent, these reagents. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; alcohols, such as methanol, ethanol and isopropanol; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane; NITRILES such as acetonitrile and propionitrile; esters, such as ethylformate and ethyl acetate; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, this reaction can be carried out under heating. The time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period sufficient for the reaction ranges from several hours to several days.

Stage B7

In Stage B7 connection Faure is wow hydrogenation or by means of reduction reaction using a metal hydride.

If the compound of the formula (R - 13) is subjected to a catalytic hydrogenation reaction, then this goal can be used any catalyst commonly used in reactions of this type, such as palladium charcoal.

This reaction is normally and preferably carried out in the presence of a solvent. This can be used any solvent, if he does not exert undesirable influence on the reaction, or it uses the reagents and if he has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, dioxane and tetrahydrofuran; alcohols such as methanol, ethanol and isopropanol; acids such as formic acid, acetic acid and propionic acid; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. Though the but from room temperature to the heating temperature. The time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several hours to several days, preferably from 1 h to 3 days.

This reaction is usually carried out at atmospheric pressure or preferably at a pressure higher than atmospheric.

If the compound of the formula (R-13) is subjected to restore using a metal hydride, the reaction can be carried out by the method described in WO 93/1309.

Stage B8

In Stage B8 compound of the formula (R-15) are obtained by reaction of compounds of formula (R-12) with hydroxylamine and subsequent reaction of recovery.

The reaction of the compound of formula (R-12) with hydroxylamine (hydrochloride) is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it has no undesirable effect on the reaction or on the underlying reagents and have the ability to dissolve at least to a certain extent specified ri heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; alcohols, such as methanol, ethanol and isopropanol, amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane; NITRILES such as acetonitrile and propionitrile; esters, such as ethylformate and ethyl acetate; amines such as pyridine and triethylamine; or mixtures of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, suitable temperatures for conducting the reaction temperature is in the range of from about room temperature to the heating temperature. The time required for this reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several hours to several days, preferably from 1 h to 3 days.

Subsequent reacts is neither A; moreover, this reaction can be carried out in the same reaction conditions and using the same reagents.

Stage B9

In Stage B9 compound of the formula (R-16) are obtained by reaction of compounds of formula (R-15) with trimethylsilylcyanation.

This reaction is normally and preferably carried out in the presence of a solvent. This can be used any solvent, if only he does not exert undesirable influence on the reaction and it uses the reagents and if it is capable of dissolving at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane; NITRILES such as acetonitrile and propionitrile; esters, such as ethylformate and ethyl acetate; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of reperatory to carry out the reaction temperature is in the range of temperature cooling with ice to a temperature of the heating and preferably the reaction is carried out at a temperature cooling with ice, or at a temperature in the range of temperature cooling with ice up to 60oC. the Time required for this reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several hours to several days, preferably from 1 h to 3 days.

Stage B10

In Stage B10 compound of the formula (R-17) are obtained by reaction of compounds of formula (R-15) with chlorocarbonylsulfenyl.

This reaction is normally and preferably carried out in the presence of a solvent. This can be used any solvent, if he does not exert undesirable influence on the reaction, or it uses the reagents and if he has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetal the 1,2-dichloroethane; NITRILES, such as acetonitrile and propionitrile; esters, such as ethylformate and ethyl acetate; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, a suitable temperature for this reaction is temperature in the range of temperature cooling with ice up to the heating temperature, and preferably at a temperature of cooling with ice or at a temperature in the range of temperature cooling with ice up to 60oC. the Time required for this reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several minutes to 1 day.

The reaction scheme C.

The following reaction scheme illustrates an alternative method for obtaining compounds of formula (R-9) (see, for example, schemes B1 and B2).

Reaction scheme C:

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In the above formulas, X, A, B, is pirta, for example t-butylmethylamine group.

Stage C1

In Stage C1, the compound of formula (R-20) are obtained by reaction of compounds of formula (R-18) and the compounds of formula (R-19).

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it does not exert undesirable influence on the reaction, or it uses the reagents and has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; alcohols, such as methanol, ethanol and isopropanol; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane; NITRILES such as acetonitrile and propionitrile; esters, such as ethylformate and ethyl acetate; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature, and preferably at a temperature of 50oC, or by heating under reflux. The time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several tens minutes to several days.

Stage C2

In Stage C2 compound of the formula (R-21) is obtained by alkylation, aralkylamines, acylation or carbamylcholine the compounds of formula (R-20). This reaction is mostly carried out in accordance with the procedure of Stage A3 of the Reaction scheme A, under the same reaction conditions and using the same reagents.

Stage C3

In Stage C3 compounds of the formula (R-9) is produced by removing the protective group Q of the compounds of formula (R-21).

This reaction is carried out using a reaction between the compounds of formula (R-12) with an acid, such as acetic acid, triperoxonane acid, hydrochloric acid or hydrofluoric acid, or through a reaction between the compounds (R-12) with a compound generating a fluorine ions, so the AC is on hydrogenation of the compounds in the presence of a solvent.

The reaction involving the interaction of this compound with an acid or a fluoride ion in the presence or in the absence of solvent, can be carried out by conventional method (for example, J. W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons; J. F. W. Mc Omie, Protective Groups in Organic Chemistry, Plenum Press).

If the compound of the formula (R-21) is subjected to a catalytic hydrogenation reaction, this reaction can be used catalyst that is commonly used in reactions of this type, such as palladium charcoal.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it does not exert undesirable influence on the reaction, or it uses the reagents and has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, dioxane and tetrahydrofuran; alcohols such as methanol, ethanol and isopropanol; acids such as formic acid, acetic acid and propionic acid; amides, such as dimethylformamide, LASS="ptx2">

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, a suitable temperature for this reaction is temperature in the range from room temperature to the heating temperature. The time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction ranges from several hours to several days, and more preferably from 1 h to 3 days.

This reaction is usually carried out at atmospheric pressure or preferably at a pressure higher than atmospheric.

The reaction scheme C1.

The compound of the formula (R-19) used in Stage C1, can be obtained as shown in Reaction scheme C1:

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< / BR>
In the above formulas, R1, R2and are the same as defined above and Boc represents a t-butoxycarbonyl group.

For example, the compound of formula (R-19) can be obtained by TA is the W and obtain the compounds of formula (R-24), and then removing the t-butoxycarbonyl group. These reactions can be carried out by standard methods (see, for example, J. W. Green, Protective Groups in Organic Synthesis, John Wiley & Sons; J. F. W. McOmie, Protective Groups in Organic Chemistry. Plenum Press).

The reaction scheme D.

This reaction scheme illustrates the method of obtaining the compounds of formula (R-27), which is a compound of formula (R-6), where A and B taken together are a carbonyl group and which can then be used as described above in Reaction scheme B.

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< / BR>
In the above formulas, X and Boc are as defined above.

Stage D1

In Stage D1 compound of the formula (R-26) receive first through reaction of compounds of formula (R-25) with sodium hydride and then with the reaction of the obtained compound with a compound of the formula (R-18).

This reaction is normally and preferably carried out in the presence of a solvent. This can be used any solvent, if he does not exert undesirable influence on the reaction, or it uses the reagents and if he has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents afir, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; gallovidian hydrocarbons, such as methylene chloride, chloroform and 1,2-dichloroethane; NITRILES such as acetonitrile and propionitrile; esters, such as ethylformate and ethyl acetate; or a mixture of any two or more of these solvents. Of them, preferred are amides.

The first stage reaction can take place in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, a suitable temperature for this reaction is temperature in the range of temperature cooling with ice to a temperature of heating. The time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from 0.5 to 5 hours

The second stage reaction may take place in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention from room temperature to 100oC. the Time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction, usually from 1 hour to several days.

Stage D2

In Stage D2 compound of the formula (R-27) are obtained by the reaction, which is subjected to the compound of formula (R-26) in order to remove the t-butoxycarbonyl group represented by Boc (for example, as described by J. W. Green, Protective Groups in Organic Synthesis, John Wiley & Sons; J. F. W. McOmie, Protective Groups in Organic Chemistry, Plenum Press).

The reaction scheme E.

This reaction scheme illustrates a method of obtaining compound (R-1), used as starting material in Reaction schemes A and B (see above).

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In the above formulas, X and Halo are as defined before.

Stage E1

In Stage E1 compound of the formula (R-30) are obtained by reaction of compounds of formula (R-29) with the compound of the formula (R-28). This reaction is usually carried out in the presence or absence of a base. This can be used any base commonly used in reactions of this is at potassium; the bicarbonates of alkaline-earth metals, such as sodium bicarbonate; hydrides of alkali metals, such as sodium hydride.

This reaction is normally and preferably carried out in the presence of a solvent. This can be used any solvent, if he does not exert undesirable influence on the reaction, or it uses the reagents and if he has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; alcohols, such as methanol, ethanol and isopropanol; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane; NITRILES such as acetonitrile and propionitrile; esters, such as ethylformate and ethyl acetate, or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. However, in anatoy temperature to the heating temperature. The time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several tens minutes to several days.

Stage E2

In Stage E2 compound of the formula (R-1) are obtained by reaction of compounds of formula (R-30) with ammonia.

This reaction is normally and preferably carried out in the presence of a solvent. For these purposes may be used any solvent provided that it does not exert undesirable influence on the reaction and it uses the reagents, and provided that he has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; alcohols, such as methanol, ethanol and isopropanol; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane is; water or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, suitable temperatures for conducting the reaction temperature is in the range of from about room temperature to the heating temperature. The time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several tens minutes to several days.

This reaction can also be carried out at atmospheric pressure or in a tightly closed container.

Stage E3

In Stage E3 compound of the formula (R-31) are obtained by reaction of compounds of formula (R-30) with Amida alkali metal such as lithium azide, sodium azide or potassium azide.

This reaction is normally and preferably carried out in the presence of a solvent. For these purposes may be used any solvent provided that it is not the ability to dissolve, at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; alcohols, such as methanol, ethanol and isopropanol; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane; NITRILES such as acetonitrile and propionitrile; esters, such as methylformate, ethylformate and ethyl acetate; water; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, a suitable temperature for this reaction is temperature in the range of from about room temperature to the heating temperature. The time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, the time period Dade E4

In Stage E4 a compound of the formula (R-1) are obtained by reaction of compounds of formula (R-31) and lithium aluminum hydride, or by catalytic hydrogenation reaction, which is subjected to the compound of formula (R-31).

The reaction of the compound of formula (R-31) with lithium aluminum hydride, usually and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it does not exert undesirable influence on the reaction, or it uses the reagents, and provided that he has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; or a mixture of any two or more of these solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, a suitable temperature for this reaction is temperature in the range of temperature cooling with ice to a temperature of heating the Ktorov, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction ranges from several tens of minutes up to 1 day.

If the compound of the formula (R-31) is subjected to hydrogenation in the presence of a catalyst, examples of such catalysts can serve as a standard hydrogenation catalysts such as palladium carbon and platinum oxide.

This reaction is normally and preferably carried out in the presence of a solvent. This can be used any solvent, if he does not exert undesirable influence on the reaction or the reagents and if he has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents include: hydrocarbons, such as benzene, toluene, xylene, hexane and heptane; ethers, such as diethyl ether, tetrahydrofuran and dioxane; alcohols, such as methanol, ethanol and isopropanol; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; halogenated hydrocarbons such as methylene chloride, chloroform and 1,2-dichloroethane; NITRILES such as acetonitrile and puff solvents.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature does not play a decisive role for the present invention. In General, however, a suitable temperature for this reaction is temperature in the range of from about room temperature to the heating temperature. The time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from several tens minutes to several hours.

This reaction is usually carried out at atmospheric pressure or preferably at a pressure higher than atmospheric.

The reaction scheme F.

The following reaction scheme illustrates an alternative method of preparing compounds of the formula (R-36), which are compounds of formula (I) of the present invention.

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< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
In the above formulas, X, A, B, R1, R2, R3, y2, R, and Halo are as defined above.

The F1 stage

In Statii Foundation.

This reaction is normally and preferably carried out in the presence of a solvent. For this purpose, can be used any solvent provided that it has no undesirable effect on the reaction or the reagents, and provided that he has the ability to dissolve at least to a certain extent, these reagents. Examples of suitable solvents are: aromatic hydrocarbons, such as benzene, toluene and xylene; ethers such as diethyl ether, tetrahydrofuran and dioxane; amides, such as dimethylformamide, dimethylacetamide and triamide hexamethylphosphoric acid; or a mixture of two or more of these solvents.

In this reaction can be used any cause, provided that it does not exert undesirable influence on the reaction; however, this base can be any base commonly used in reactions of this type. Examples of suitable bases are sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, diisopropylamide utility and lithium.

This reaction may proceed in a wide range of temperatures, and the precise value of the reaction temperature is not R is the reaction temperature is in the range of temperature cooling with ice to a temperature of heating. The time required to perform the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents. However, in most cases, a period of time sufficient for the reaction is from 1 h to several days.

Stage F2

In Stage F2 compound of the formula (R-33) is obtained by recovery of the compounds of formula (R-32).

This reaction can be carried out by catalytic hydrogenation or by reduction of the nitro group using zinc-acetic acid or tin-hydrochloric acid.

Stage F3

In Stage F3 compound of the formula (R-34) are obtained by reaction of arilirovaniya of Meerwein, which is subjected to the compound of formula (R-33). This reaction is usually carried out by the method described in the prior publication of a patent Japan (Coca) N Sho 55-22657, and by the method of S. Oae and others (Bull. Chem. Soc. Jpn., Vol. 53, page 1065 (1980)).

Stage F4

In Stage F4 compound of the formula (R-35) are obtained by reaction of compounds of formula (R-34) with the compound of the formula

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where

Y2represents an oxygen atom or a sulfur atom.

The compound obtained of the formula (R-35) could you be the formula (R-36) are obtained by catalyzed reaction, acid hydrolysis, which is subjected to the compound of formula (R-35). Stage F4 and F5 are usually carried out by the method described in the prior publication of the Japan patent (Kokai) N Sho 55-22657.

After completing any of the above reactions, the desired compounds obtained in the respective stages can be purified by standard methods such as column chromatography, recrystallization, pereosazhdeniya or any combination thereof. For example, in one suitable procedures for isolation, the reaction mixture was extracted by adding solvent, after which the solvent is evaporated from the extract. Then the precipitate is introduced into the chromatographic column, for example, silica gel, and get purified target compound.

Biological activity.

In the tested system using animals with congenital diabetes compounds of the present invention showed high gipoglikemicescuu activity. It is therefore evident that the compounds of the present invention can be used for the treatment and/or prevention of diabetes; complications associated with diabetes; hyperlipidemia; hypertension associated with obesity; osteoporosis, etc.

Compounds of the present invention may be the soedineniya are intended for oral administration, they can be made in the form of tablets, capsules, granules, powders or syrups; and if the connectors are designed for parenteral administration, they can be manufactured by injection (intravenous, intramuscular or subcutaneous), drops or suppositories. For the treatment of mucous membranes in the eyes of the compounds of the present invention can be introduced in the form of eye drops or ointments. These preparations can be manufactured by standard methods, and, if necessary, the active ingredient can be mixed with any conventional additive such as a filler, binder, disintegrator, lubricant, corrective tool, solubilizers agent, suspendida additive, emulsifying tool or means to cover. Although the injected dose of the compounds of the present invention may vary depending on symptoms, age and body weight of the patient, nature and severity of the disease, the route of administration and the form of a medicinal product intended for the treatment of diabetes, its complications and/or hyperlipemia, however, the daily dose recommended for the introduction of an adult ranges from 0.01 to 2000 mg of this compound and can be entered as a single dose or divided is the cops.

Experiment 1. Hypoglycemic activity

As the test animals used of male mice with hyperglycemia (strain QC), each of which had a body weight of more than 40 g Each animal orally was administered the test compound in the amount indicated in the following table 8, and then gave feed the desire for 18 hours, after this time from the tail vein of the animal without anesthesia took the blood. The level of blood glucose (BGL) was determined using the analyzer blood glucose (GL-101, manufactured by Mitsubishi Kasei Co. or GGT or manufactured Shino-Test Co.).

The reduction in blood glucose was calculated by the following equation:

the reduction in blood glucose (%)=(BGLs=BGLt)/BGLs100, where BGLsis a BGL for a group of animals who were injected only one solvent and did not enter active compounds, and BGLtis a BGL for a group of animals that were administered the test compound.

The results obtained are shown in table 8, in which each connection of the present invention designated by the number of the example, which describes the receipt of this connection.

As can be seen from table 8, the compounds of this is their alsoreported

Alsoreported bovine eye lens was isolated and partially purified by the method of S. Hyman & J. H. Kinoshita, y.Biol. Chem., 240, 877 (1965) and K. Inagaki. I. Miwa & J. Okuda, Arch. Biochem. Biophys., 316, 337 (1982) and its activity was determined photometrically according to the method of Varma and others (Biochem. Pharmac., 25, 2505 (1976)). Inhibition of enzyme activity was measured when the concentration of the compounds of the present invention 5 μg/ml and the results of these measurements are presented in table 9.

Experiment 3. Toxicity

The toxicity of the compounds of the present invention was tested on rats male F344, which were divided into groups consisting of 5 animals. Each animal orally for 2 weeks were administered the test compound at a dose of 50 mg per kg of body weight. As the test compounds used compounds of examples 20, 45 (polar, less polar) and 47 (polar). Animals were monitored over the next 2 weeks and during this period of time in animals have not revealed any abnormalities that could be attributed to the action of the tested compounds. When hematological studies have found only a small decrease in the number of red blood cells, which could be attributed to the action of the compound of example 45 (less polyarnoe animals indicates, the compounds of the present invention have low toxicity.

Thus, the compounds of the present invention have a high activity and at the same time very low toxicity, which makes them ideal for use in therapeutic purposes.

The present invention also is illustrated by the following examples, not limiting, however, the scope of the present invention. In these examples, connections numbers coincide with the numbers of the compounds presented in tables 1-7 (see above). Getting some of the original materials used in some of these examples are illustrated in the making, following the examples. The specific value of the angle of rotation were obtained by measurement at room temperature.

Example 1. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2-oxo-oxazolidin-3-yl)propoxy]benzyl} thiazolidine-2,4-dione (Compound 1-94 N)

To 330 mg 5-{4-[2-(5-3'-chlorphenoxamine-2-oxoacridine-3-yl)propoxy] benzyl}- 3-triphenyltetrazolium-2,4-dione (obtained in accordance with the description given in Obtaining 6) under ice cooling was added 3 ml triperoxonane acid and the resulting mixture was stirred at room temperature for 2 the sodium, and then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride, and then dried with anhydrous sodium sulfate. Thereafter, the ethyl acetate was removed from the extract by evaporation under reduced pressure. The obtained residue was purified by column chromatography on silica gel, using as eluent a mixture of f and hexane (2:3 by volume), resulting in a received 160 mg of target compound having so pl. 50,9o-52,5oC and Rf= 0,45 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 2:1 by volume).

Example 2. 5-{4-[2-(3-3'-Chlorophenoxy-2-hydroxypropylamino)propoxy]benzyl}thiazolidine-2,4-dione (Compound 1-92 N)

To a solution of 100 mg 3-(3-chlorophenoxy)-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 13) and 139 mg of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2,4-dione in 3 ml of anhydrous methanol under ice cooling was added 148 mg laborgerate sodium. The resulting mixture was stirred at room temperature for 7 h in a stream of nitrogen gas. After this time the reaction mixture was left overnight, and then poured into water and extraheavy the aqueous sodium sulfate. After that, the solvent was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by thin layer chromatography on silica gel, using as manifested solvent mixture of ethyl acetate and ethanol (8:1 by volume). Thus received 92 mg of the target compound with Rf= 0,30 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol, 10:1 by volume).

Example 3. 5-{4-[2-(3-phenoxy-2-hydroxypropylamino)-propoxy]benzyl}thiazolidine-2,4-dione (Compound 1-16 N)

Repeating the procedure described in Example 2, except that used 0,98 g 3 phenoxy-2-hydroxypropylamino (obtained in accordance with the description given in the Receive 15), 3,39 g of 5-[4-(2-oxopropoxy)-benzyl] thiazolidin-2,4-dione, 1,11 g cyanoborohydride sodium and 60 ml of anhydrous methanol. The crude product was purified by chromatography on a column and silica gel, using as eluent a mixture of ethyl acetate and ethanol (10:1 by volume), resulting in a received 1.92 g of target compound with so pl. 64-68oC.

Example 4. 5-{4-[2-(5-Phenoxymethyl-2-oxoacridine - 3-yl)propoxy]benzyl} thiazolidine-2,4-dione (obtained in accordance with the description, shown in Example 3) in 5 ml of anhydrous dimethylformamide under ice cooling was added 211 mg of N,N'-carbonyldiimidazole and the resulting mixture was stirred at room temperature for 5 hours. After this time, the dimethylformamide was removed from the reaction mixture by evaporation under reduced pressure. Once added to the obtained residue, water the mixture was extracted with ethyl acetate. After that, the extract was washed with an aqueous solution of sodium chloride, and then dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (2:1 to 1:1 by volume), resulting in a received 410 mg of target compound having so square 54 - 56oC.

Example 5. 5-{4-[2-(3-3'-Chlorophenoxy-2-hydroxypropylamino) ethoxybenzyl} thiazolidin-2,4-dione (Compound 1-91 N)

Repeating the procedure described in Example 2, except that used 600 mg of 3-(3-chlorophenoxy)-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 13), 800 mg of 5-[4-(2-oksidoksi)benzyl] thiazolidin-2,4-dione (obtained in sootvetchikom received 180 mg of the target compound, with Rf= 0,35 (thin layer chromatography on silica gel using as developing solvent a mixture of ethanol and ethyl acetate, 1 : 4 by volume).

Example 6. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2-oxoacridine - 3-yl)propoxy]benzyl}thiazolidine-2,4-dione (Compound 1-93 N)

Repeating the procedure described in Example 4, except that used 180 mg 5-{4-[2-(3-3'-chlorophenoxy-2 - hydroxypropylamino)ethoxy] benzyl} thiazolidine-2,4-dione, (obtained in accordance with the procedure described in Example 5), 65 mg of N,N'-carbonyldiimidazole and 10 ml of anhydrous dimethylformamide, resulting in received 53 mg of target compound having so pl. 58 - 63oC and Rf= 0,27 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 2:1 by volume).

Example 7. 5-{4-[2-(3-Phenyl-2-hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (Compound No. 1-2)

500 mg of 3-phenyl-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 17) and 1.0 mg of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2,4-dione suspended in 30 ml of anhydrous benzene, and the resulting suspension was heated under reflux for 30 mi oily product was dissolved in 20 ml of anhydrous methanol and to the obtained solution under cooling with ice) was added 670 mg cyanoborohydride sodium. After that, the mixture was stirred for 2 h in a stream of nitrogen gas. Then the reaction mixture was stirred overnight, after which the solvent was removed by evaporation under reduced pressure. To the residue was added water and the mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, and then dried with anhydrous sodium sulfate. The solvent was removed from the extract by evaporation under reduced pressure and the resulting residue was introduced into a chromatographic column with silica gel (elwira a mixture of ethyl acetate and methanol, 5:1 by volume), after which he led from ethyl acetate, resulting in a received 590 mg of the target compound, so pl. 145 - 152oC.

Example 8. 5-{4-[2-(5-Benzyl-2-oxoacridine - 3-yl)propoxy]benzyl}thiazolidine-2,4-dione (Compound 1-4 N)

Repeating the procedure described in Example 4, except that used 300 mg 5-{4-[2-(3-phenyl-2 - hydroxypropylamino)propoxy]benzyl} thiazolidine-2,4-dione, (obtained in accordance with the description given in Example 7), 120 mg of N,N'-carbonyldiimidazole and 10 ml of anhydrous dimethylformamide. The product was chromatographically on a column of silica gel, using as eluent to shift the C.

Example 9. 5-{4-[2-(3-3'-Chlorophenoxy-2-hydroxypropylamino) propylthio]benzyl}thiazolidine-2,4-dione (Compound N 1-158)

Repeating the procedure described in Example 2, except that used 1.0 g of 3-(3-chlorophenoxy)-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 13, 1.5 g of 5-[4-(2-oxopropyl)benzyl] thiazolidin-2,4-dione (obtained in accordance with the description given in Obtaining 18), 940 mg of cyanoborohydride of sodium and 30 ml of anhydrous methanol. The crude product was chromatographically on a column of silica gel, using as eluent a mixture of ethyl acetate and ethanol (10:1 by volume), resulting in received of 1.52 mg of target compound with Rf= 0,44 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol, 10:1 by volume).

Example 10. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2-oxoacridine - 3-yl)propylthio]benzyl}thiazolidine-2,4-dione (Compound N 1-159)

Repeating the procedure described in Example 4, except that used 300 mg 5-{4-[2-(3-3'-chlorophenoxy-2-hydroxypropylamino) propylthio] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in PR is Ali using column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (3: 2 by volume), resulting in a received separately the more polar diastereoisomer and less polar diastereoisomer. The corresponding diastereomers was purified using reverse-phase preparative liquid chromatography high resolution [column UMC-pack ODS-A (trademark of a product manufactured by the firm of SMC Co.); eluent is a mixture of acetonitrile, water, acetic acid and triethylamine, 100:100:1:1 by volume)], resulting from the more polar diastereoisomer was obtained 110 mg of the target compound with Rf= 0,15 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume), and the less polar diastereoisomer was obtained 120 mg of target compound with Rf= 0,25 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume).

Example 11. 5-[4-{2(R)-[5(S)-(3-Chlorphenoxy)- 2-oxoacridine-3-yl]propoxy}benzyl]thiazolidin-2,4-dione (Compound 1-94 N)

Repeating the procedure described in Example 1, except that used 0.96 g of 5-[4-{2(R)-[5(S)-(3-chlorphenoxy)- 2-oxoacetate in Obtaining 29), 4 ml of methylene chloride and 4 ml triperoxonane acid. Thus was obtained 0.52 g of target compound having so pl. 48 - 53oC (softening) with []D= +54o(methanol, C = 1,000).

Example 12. 5-[4-{2(S)-[5(R)-(3-Chlorphenoxy)- 2-oxoacridine-3-yl]propoxy}benzyl]thiazolidin-2,4-dione (Compound 1-94 N)

Repeating the procedure described in Example 1, except that used to 0.73 mg of 5-[4-{2(S)-[5(R)-(3-chlorphenoxy)- 2-oxoacridine-3-yl] propoxy}benzyl]-3-triphenyltetrazolium - 2,4-dione (obtained in accordance with the description given in Obtaining 37), 4 ml of methylene chloride and 4 ml triperoxonane acid, resulting in a received 0.39 g of target compound having so pl. 55 - 60oC (softening) with []D= -52,4o(methanol, C = 0,990).

Example 13. 5-[4-{2(S)-[5(S)-(3-Chlorphenoxy)- 2-oxoacridine-3-yl]propoxy}benzyl]thiazolidin-2,4-dione (Compound 1-94 N)

Repeating the procedure described in Example 1, except that used 0,57 mg 5-[4-{2(R)-[5(R)-(3-chlorphenoxy)- 2-oxoacridine-3-yl] propoxy}benzyl]-3-triphenyltetrazolium - 2,4-dione (obtained in accordance with the description given in Obtaining 45), 2 ml triperoxonane acid and 2 ml]D= = -39,7o(methanol, C = 0,965).

Example 14. 5-[4-{2(R)-[5(R)-(3-Chlorphenoxy)- 2-oxoacridine-3-yl]propoxy}benzyl]thiazolidin-2,4-dione (Compound 1-94 N)

Repeating the procedure described in Example 1, except that used 0,57 g of 5-[4-{2(R)-[5(R)-(3-chlorphenoxy)- 2-oxoacridine-3-yl] propoxy}benzyl]-3-triphenyltetrazolium - 2,4-dione (obtained in accordance with the description given in Obtaining 45), 2 ml triperoxonane acid and 2 ml of methylene chloride. Thus was obtained target compound (280 mg) with so pl. 52 - 53oC.

[]D= -39,7o(methanol, C = 0,965).

Example 15. 5-{4-[2-(3-Benzyloxy-2-hydroxypropylamino)propoxy] benzyl} thiazolidine-2,4-dione (Compound N 1-64)

Repeating the procedure described in Example 2, except that used 545 mg of 3-benzyloxy-2-hydroxypropylamino (obtained in accordance with the description provided in the Receiving 48), 700 mg of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2,4 - dione, 470 mg of cyanoborohydride sodium and 60 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, elwira gradient mixture of ethyl acetate and ethanol (10:1 to 5:1 by volume. In addition, the resulting product is RGBY the sign of the product, produced by YMC Co. ), using as eluent a mixture of acetonitrile, water, acetic acid and triethylamine (50:1:1 by volume), which was obtained 130 mg of the desired product as a pale yellow glassy solid, with Rf= 0,16 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol, 10:1 by volume).

Example 16. 5-{4-[2-(3-5-Phenylmethoxy-2-hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (Compound N 1-160)

Repeating the procedure described in Example 2, except that used 820 mg of 3-(5-phenylmethoxy)-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 51), 840 mg of 5-[4-(2-oxopropyl)benzyl] thiazolidin-2,4-dione, 540 mg of cyanoborohydride sodium and 80 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, elwira gradient mixture of ethyl acetate and ethanol (10:1 to 5:1 by volume). The resulting product was purified using reverse-phase preparative liquid chromatography high resolution (YMC-pack ODS-A-trademark of a product manufactured by the company YMC Co. using as the 250 mg of the target compound as pale yellow oily substance, with Rf= 0,35 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol (5:1 by volume)).

Example 17. 5-{4-[2-(3-3'-Phenylpropoxy-2-hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (Compound 1-74 N)

Repeating the procedure described in Example 2, except that used 720 mg of 3-(3-phenylpropoxy)-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 54), 800 mg of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2-4-dione, 540 mg of cyanoborohydride sodium and 70 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and ethanol (10: 1 to 5:1 by volume). Then the obtained product was purified using reverse-phase preparative liquid chromatography high resolution (YMC-Pack ODS-A-trademark of a product manufactured by the company YMC Co. ), using as eluent a mixture of acetonitrile, water, acetic acid and triethylamine (50:50:1:1 by volume), resulting in a received 380 mg of the target compound as a pale yellow glassy solid, with Rf= 0,29 (thin layer of chromate volume).

Example 18. 5-{ 4-[2-(3-2'-Venlafaxi-2-hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (Compound N 1-69)

Repeating the procedure described in Example 2, except that used 0,70 g 3-(2-phenylethane)-2-hydroxypropylamino (obtained in accordance with the procedure described in Obtaining 57), and 1.00 g of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2,4-dione, 0.71 g cyanoborohydride of sodium and 20 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, using as eluent ethyl acetate. The result of this procedure was given to 0.92 g of target compound having so pl. 46 - 49oC (softening).

Example 19. 5-{ 4-[2-(3-4'-Phenylmethoxy-2-hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (Compound N 1-161)

Repeating the procedure described in Example 2, except that used 1.20 g of 3-(4-phenylmethoxy)-2-hydroxypropylamino (obtained in accordance with the description given in the completion of 60), and 1.00 g of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2,4-dione, 0.71 g cyanoborohydride of sodium and 20 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of e oC (softening).

Example 20. 5-{4-[2-(3-6-Phenylhexane-2-hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (Compound N 1-162)

Repeating the procedure described in Example 2, except that used 864 mg of 3-(6-phenylhexanoic)-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 63), 800 mg of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2,4-dione, 540 mg of cyanoborohydride of sodium and 50 ml of anhydrous methanol. The crude product was purified by chromatography on a column of silica gel, using as eluent a gradient mixture of ethyl acetate and ethanol (1:0 to 5:1 by volume), resulting in a received 500 mg of the target compound as pale yellow oily substance having Rf= 0,42 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol 5:1 by volume).

Example 21. 5-{4-[2-(3-8'-Phenylacrylate-2-hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (Compound N 1-163)

Repeating the procedure described in Example 2, except that used 0.96 g of 3-(8-phenylacrylate)-2-hydroxypropylamino (obtained in accordance with the description given in Polozola. The crude product was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and ethanol (10:1 to 5:1 by volume). The result of this procedure received 360 mg of target compound with Rf= 0,43 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol 5:1 by volume).

Example 22. 5-{4-[2-(5-Benzoyloxymethyl-2-oxoacridine-3-yl)propoxy] benzyl}thiazolidine-2,4-dione (Compound N 1-164)

Repeating the procedure described in Example 4, except that used 200 mg 5-{4-[2-(3-benzyloxy-2-hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (obtained in accordance with the procedure described in Example 15), 73 mg of N,N'-carbonyldiimidazole and 20 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, elwira gradient mixture of ethyl acetate and hexane (2: 1 to 3:1 by volume). The result of this procedure were given 160 mg of the target compound as a pale yellow glassy solid, which is a mixture of the less polar diastereoisomer, with Rf= 0,49 (thin-layer storage, 3:1 by volume), and more polar diastereoisomer, with Rf= 0,38 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 3:1 by volume).

Example 23. 5-{4-[2-(5-2'-Venlafaxine-2-oxoacridine-3-yl) propoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-165)

Repeating the procedure described in Example 4, except that used 700 mg 5-{4-[2-(3-2'-venlafaxi-2-hydroxypropylamino) propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 18), 250 mg of N,N'-carbonyldiimidazole and 10 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of hexane and ethyl acetate (1: 1 by volume), resulting in a received 650 mg of target compound in the form of a mixture (1:1) polar diastereoisomer, with Rf= 0,74 (thin layer chromatography on silica gel using as eluent ethyl acetate), and the less polar diastereoisomer, with Rf= 0,80 (thin layer chromatography on silica gel using ethyl acetate as eluent).

Example 24. 5-{4-[2-(5-3'-Phenylpropoxy annoy in Example 4, except that used 600 mg 5-{ 4-[2-(3-3'-phenylpropoxy-2-hydroxypropylamino) propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 17), 206 mg of N,N'-carbonyldiimidazole and 60 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and hexane (1:1 to 3:2 by volume), resulting in a received separately polar diastereoisomer and less polar diastereoisomer. The corresponding diastereomers was purified using reverse-phase preparative liquid chromatography high resolution (YMC-Pack ODS-A-trademark of a product manufactured by the company YMC Co.), using as eluent a mixture of acetonitrile and water (1:1 by volume). The result of this procedure from the polar diastereoisomer was obtained 98 mg of the target compound with Rf= 0,46 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 2:1 by volume), and the less polar diastereoisomer was obtained 189 mg of the target compound with Rf= 0,52 (thin layer chromatography on silica gel using as simetal-2-oxoacridine-3-yl) propoxy]benzyl}thiazolidine-2,4-dione (Compound 1-79 N)

Repeating the procedure described in Example 4, except that used 550 mg 5-{4-[2-(3-4'-phenylmethoxy-2-hydroxypropylamino) propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 19), 180 mg of N,N'-carbonyldiimidazole and 10 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of hexane and ethyl acetate (2:1 by volume). Then the product was purified using reverse-phase preparative liquid chromatography high resolution (YMC-Pack ODS-A-trademark of a product manufactured by the company YMC Co.), using as eluent a mixture of acetonitrile, water, acetic acid and triethylamine (100: 100: 1:1 by volume), resulting in the received polar diastereoisomer and less polar diastereoisomer. From polar diastereoisomer was obtained 170 mg of the target compound with Rf= 0,71 (thin layer chromatography on silica gel using as a developing solvent ethyl acetate), and the less polar diastereoisomer was obtained 160 mg of target compound with Rf= 0,79 (thin layer chromatography on silica gel using as proyavlyayuschego the si]benzyl}thiazolidine-2,4-dione (Compound N 1-167)

Repeating the procedure described in Example 4, except that used 600 mg 5-{ 4-[2-(3-5'-phenylmethoxy-2-hydroxypropylamino) propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 16), for 194.3 mg N,N'-carbonyldiimidazole and 60 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (2:1 by volume). The result of this procedure received 520 mg of the target compound as pale yellow oily substance, which is a mixture of the less polar diastereoisomer, with Rf= 0,61 (thin layer chromatography on silica gel using mixtures of ethyl acetate and hexane (2:1 by volume) as the developing solvent) and the polar diastereoisomer, with Rf= 0,52 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 2:1 by volume).

Example 27. 5-{ 4-[2-(5-6'-Vanillacracker-2-oxoacridine-3-yl) propoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-168)

Repeating the procedure described in Example 4, except that easen in accordance with the description, Example 20), 217 mg of N,N'-carbonyldiimidazole and 20 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:1 to 3:2 by volume), resulting in a received 520 mg of the target compound as pale yellow oily substance, which is a mixture of the less polar diastereoisomer, with Rf= 0,63 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 3:2 by volume) and the polar diastereoisomer, with Rf- 0,56 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 3:2 by volume).

Example 28. 5-{ 4-[2-(5-8'-Phenylanthracene-2-oxoacridine-3-yl)propoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-169)

Repeating the procedure described in Example 4, except that used 660 mg 5-{ 4-[2-(3-8'-phenylacrylate-2-hydroxypropylamino)propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 21), 197 mg of N,N'-carbonyldiimidazole and 20 ml of anhydrous dimethylformamide eluent mixture of ethyl acetate and hexane (1:1 by volume). The result of this procedure received 550 mg of the target compound in the form of a mixture of polar diastereoisomer, with Rf= 0,58 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 3:2 by volume) and the less polar diastereoisomer, with Rf- 0,65 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 3:2 by volume).

Example 29. 5-{ 4-[2-(5-7'-Vanillacracker- -2-oxoacridine-3-yl)propoxy]-benzyl}-thiazolidine-2,4-dione (Compound N 1-170)

Repeating the procedure described in Example 4, except that used 590 mg 5-{ 4-[2-(3-7'-phenylheptane-2-hydroxypropylamino)propoxy] benzyl] thiazolidin-2,4-dione (obtained in accordance with the description given in Example 56), 181 mg of N,N'-carbonyldiimidazole and 15 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:1 by volume), resulting in a received 383 mg of the target compound in the form of a mixture of polar diastereoisomer, with Rf= 0,29 (thin layer chromatography n) and the less polar diastereoisomer, with Rf= 0,37 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume).

Example 30. 5-{ 4-[2-(5-3'-Forfinancial-2- -oxoacridine-3-yl)propoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-171)

Repeating the procedure described in Example 1, except that used 390 mg 5-{4-[2-(5-3'-forfinancial)-2-oxoacridine-3-yl)propoxy] benzyl} - 3-triphenyltetrazolium-2,4-dione (obtained in accordance with the description given in Getting 74), 2 ml triperoxonane acid and 2 ml of methylene chloride. Thus received 200 mg of target compound with so pl. 50-53oC.

Example 31. 5-{ 4-[2-(5-4'-Methoxyphenoxy - 2-oxoacridine-3-yl)propoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-173)

(a) Repeating the procedure described in Example 1, except that used to 0.68 g of 5-{4-[2-5-4'-methoxyphenoxy-2-oxoacridine-3-yl)propoxy] benzyl} -3-triphenyltetrazolium-2,4-dione (less polar isomer), obtained in accordance with the description given in Getting 78(a), 2 ml triperoxonane acid and 2 ml of methylene chloride. Thus, from the less polar diastereoisomer was obtained 280 mg televeien, what used 840 mg 5-{4-[2-(5-4'-methoxyphenoxy-2-oxoacridine-3-yl)propoxy] benzyl} -3-triphenyltetrazolium-2,4-dione (polar isomer), obtained in accordance with the description given in Getting 78(b), 2 ml triperoxonane acid and 2 ml of methylene chloride. Thus, from the polar diastereoisomer was obtained 440 mg of the target compound with so square 54-58oC.

Example 32. 5-{ 4-[2-(3-3'-Dimethylaminoethoxy-2-hydroxypropylamino)propoxy]benzyl} -thiazolidine-2,4-dione (Compound N 1-176)

Repeating the procedure described in Example 2, except that used 1.20 g of 3-(3-dimethylaminopropoxy)-2-hydroxypropylamino (obtained in accordance with the description given in Getting 81), of 1.81 g of 5-[4-(2-oxopropoxy]thiazolidin-2,4-dione, 0.96 g of cyanoborohydride of sodium and 50 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and ethanol (20:1 by volume). After recrystallization from ethanol was obtained 0.74 g of the target compound, so pl. 92,1-98oC.

Example 33. 5-{4-[2-(5-3'-Dimethylaminoethoxy-methyl-2-oxoacridine-3-yl)propoxy] -benzyl}thiazolidine-2,4-dione(Compound N 1-177)

Repeating polipropileno] propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description, Example 32), 195 mg of N,N'-carbonyldiimidazole and 5 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (2: 1 by volume), resulting in a received 380 mg of the target compound, so pl. 55,5-57,1oC.

Example 34. 5-{4-[2-(3-4'-Phenyleneoxy-2-hydroxy-propylamino)propoxy] benzyl} thiazolidine-2,4-dione (Compound N 1-179)

Repeating the procedure described in Example 1, except that used to 1.00 g of 3-(4-phenyleneoxy)-2-hydroxypropylamino (obtained in accordance with the description given in Getting 84), of 1.46 g of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2,4-dione, 0.52 g of sodium borohydride and 40 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and methanol (1:0 to 10:1, by volume). Then the obtained product was purified using reverse-phase liquid chromatography (eluent is a mixture of acetonitrile and water, 1:1 by volume) as described in Example 10, resulting in a received 174 mg of the target compound with so pl. 76,7-80,3oC.

Example 35. 5-{ 4-[2-(5-4'-Phenylphenoxide-th in Example 4, except that used 500 mg 5-{ 4-[2-(3-4'-phenyleneoxy-2-hydroxypropylamino)propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 34), 195 mg of N,N'-carbonyldiimidazole and 10 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (3:2 by volume), resulting in received of 0.44 g of the target compound, so pl. 73,1-75,4oC.

Example 36. 5-{ 4-[2-(5-4'-Phenylphenoxide-2-thiooxamate - 3-yl)propoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-181)

To a solution of 500 mg 5-{ 4-[2-(3-4'-phenyleneoxy-2-hydroxypropylamino)propoxy] benzyl} thiazolidine-2,4 - dione (obtained in accordance with the description given in Example 34) in 10 ml of anhydrous methylene chloride was added 218 mg of N,N'-thiocarbonyldiimidazole and the resulting mixture was stirred at room temperature for one hour. After this time the reaction mixture was added water and the mixture was extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate, after which the ethyl acetate was removed by evaporation under reduced pressure. The obtained residue was purified by colonos the resulting product was purified using reverse-phase liquid chromatography (eluent - a mixture of acetonitrile and water, 60:40 by volume), described in Example 10, resulting in a received 136 mg of target compound (so pl. 58,7-60,8oC) of the polar diastereoisomer and 165 mg of target compound (so pl. 177,6 - 180,3oC) of the less polar diastereoisomer.

Example 37. 5-{4-[2-(3-Phenylthio-2-hydroxypropylamino)propoxy] benzyl} thiazolidine-2,4-dione (Compound N 1-182)

Repeating the procedure described in Example 2, except that used 2,95 g 3 phenylthio-2-hydroxypropylamino (obtained in accordance with the description given in Getting 87), 3 g of 5-[4-(2 - oxopropoxy)benzyl]thiazolidin-2,4 dione, 1.0 g of cyanoborohydride of sodium and 100 ml of anhydrous methanol, resulting in a received 1,74 g of target compound, so pl. 176-177oC.

Example 38. 5-{4-[2-(5-Phenylthiomethyl-2-oxoacridine-3-yl)propoxy]benzyl}- thiazolidine-2,4-dione (Compound 1-128 N)

Repeating the procedure described in Example 4, except that used 1.2 g 5-{4-[2-(3-phenylthio-2-hydroxypropylamino) propoxy]benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 37), 0.52 g of N,N'-carbonyldiimidazole and 20 ml of anhydrous dimethylformamide. The result of this procedure was given to 1.15 g of the target link is using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume), and the less polar diastereoisomer, with Rf= 0,38 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume).

Example 39. 5-{ 4-[2-[3-(N-Methyl-N-phenylamino)-2 - hydroxypropylamino] propoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-183)

Repeating the procedure described in Example 2, except that used 1.55 g of 3-(N-methyl-N-phenylamino)-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 90), 1.6 g of 5-[4-(2-oxopropoxy)benzyl] thiazolidin-2,4-dione, 0.4 g of cyanoborohydride of sodium and 50 ml of anhydrous methanol, resulting in a received 1.39 g of target compound, so pl. 115 - 125oC.

Example 40. 5-{4-[2-[5-(N-Methyl-N-phenyliminomethyl)-2 - oxoacridine-3-yl propoxy]-benzyl}thiazolidine-2,4-dione (Compound N 1-184)

Repeating the procedure described in Example 4, except that used 0.9 g 5-[4-[2-[3-(N-methyl-N-phenylamino)-2 - hydroxypropylamino] propoxy] benzyl]thiazolidin-2,4-dione (obtained in accordance with the description given in Example 39), 0.36 g of N,N'-carbonyldiimidazole and 20 ml of anhydrous dimethylformamide. Thus was obtained 0.6 g of target compound, avorites mixture of ethyl acetate and hexane, 1:1 by volume).

Example 41. 5-{4-[2-(3-3'-Chlorobenzoyloxy-2 - hydroxypropylamino)propoxy] benzyl}thiazolidine-2,4-dione (Compound N 1-186)

Repeating the procedure described in Example 2, except that used 3.00 g of 3-(3-chlorobenzoyloxy)-2-hydroxypropylamino with purity equal to 57% (obtained in accordance with the description given in Getting 93), of 5.00 g of 5-[4-(2-oxopropoxy)benzyl]thiazolidin-2,4-dione, 2.64 g of cyanoborohydride of sodium and 100 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and ethanol (10:1 to 4:1 by volume). Then the product was purified using reverse-phase column chromatography, using as eluent a mixture of acetonitrile and water (3:7 by volume), resulting in a received 302 mg of target compound having a temperature of 52 - 53oC (softening).

Example 42. 5-{ 4-[2-(5-3'-Chlorobenzylidene-2-oxoacridine-3 - yl)propoxy]benzyl]thiazolidin-2,4-dione (Compound N 1-187)

Repeating the procedure described in Example 4, except that used 300 mg 5-{ 4-[2-(5-3'-chlorobenzoyloxy-2- -hydroxypropylamino(propoxy]benzyl}thiazolidine-2,4-dione (poluchilposle. The crude product was chromatographically on a column of silica gel, using as eluent a gradient mixture of ethyl acetate and hexane (3:2 to 2:1 by volume), resulting in a received 206 mg of the target compound with Rf= 0,25 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 2:1 by volume).

Example 43. 5-{4-[2-(5-3'-Chlorobenzylidene-2-thioxothiazolidin - 3-yl)propoxy]-benzyl}thiazolidine-2,4-dione (Compound N 1-188)

Repeating the procedure described in Example 36, except that used 300 mg 5-[4-[2-(3,3'-chlorobenzoyloxy)-2 - hydroxypropylamino)propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 41), 125 mg of N,N of thiocarbonyldiimidazole and 5 ml of anhydrous methylene chloride. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (2: 3 by volume), resulting in the received 191 mg of the target compound with Rf= 0,35 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 2:1 by volume).

Example 45. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2 - thioxothiazolidin-3-yl)propoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-95)

Repeating the procedure described in Example 36, except that used 300 mg 5-{ 4-[2-(3-3'-chlorophenoxy-2 - hydroxypropylamino)propoxy] benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 2), 127 mg of N,N'-thiocarbonyldiimidazole and 5 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (2:3 by volume). Then the product was purified using reverse-phase column chromatography (eluent is a mixture of acetonitrile and water, 1:1 by volume), so opisanie pl. 50,3 - 52,8oC, and the less polar diastereoisomer was obtained 78 mg of the target compound with so pl. 50,6 - 53,1oC.

Example 46. 5-[4-[2-(3-3'-Chlorophenoxy)-2 - hydroxypropylamino)butoxy]-benzyl}thiazolidine-2,4-dione (Compound N 1-190)

Repeating the procedure described in Example 2, except that used 1.50 g (3-(3-chlorophenoxy)-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 13), 2,61 g of 5-[4-(2-oxobutanoic)benzyl] thiazolidin-2,4-dione (obtained in accordance with the description given in Obtaining 95), 1.40 g of cyanoborohydride sodium and 40 ml of anhydrous methanol. The crude product was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and ethanol (1:0 to 10:1 by volume), after which this product was purified using reverse-phase column chromatography (eluent is a mixture of acetonitrile and water, 3:7 by volume) described in Example 1. Thus received of 2.97 g of target compound having so pl. 49,5 - 52,8oC (softening).

Example 47. 5-{4-[2-(5-3'-Chlorphenoxamine-2-oxoacridine-3 - yl)butoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-191)

Repeating the procedure described in Example 4, for is-dione (obtained in accordance with the procedure described in Example 46), 2,11 g N,N'-carbonyldiimidazole and 60 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, as eluent using a gradient mixture of ethyl acetate and hexane (2:3 to 2:1 by volume). Then the product was purified using reverse-phase column chromatography (eluent is a mixture of acetonitrile and water, 9:11 by volume), described in Example 10. The result of this procedure from the polar diastereoisomer was obtained at 1.91 g of target compound (so pl. 150,5 - 154,4oC), and the less polar diastereoisomer was obtained 1,90 g of target compound with so pl. 54,4 - 55,4oC (softening).

Example 48. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2-thioxothiazolidin - 3-yl)butoxy]-benzyl}thiazolidine-2,4-dione (Compound No. 1 -192)

Repeating the procedure described in Example 36, except that used 250 mg 5-{ 4-[2-(3-3'-chlorophenoxy-2 - hydroxypropylamino)butoxy]benzyl}thiazolidine-2,4-dione (obtained in accordance with the description given in Example 46), 102 mg of N,N'-thiocarbonyldiimidazole and 5 ml of methylene chloride. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and Gex is as eluent a mixture of acetonitrile and water (1: 1 by volume), as described in Example 10. The result of this procedure from the polar diastereoisomer was obtained 87 mg of the target compound with so pl. 54,1 - 56,0oC, and the less polar diastereoisomer was obtained 85 mg of target compound having so pl. 57,7 - 59,0oC.

Example 49. 5-{4-[2-(5-Phenoxymethyl-2-dioxoimidazolidin-3 - yl)propoxy] -benzyl}thiazolidine-2,4-dione (Compound N 1-51)

Repeating the procedure described in Example 36, except that used 205 mg 5-{4--[2-(3-phenoxy-2 - hydroxypropylamino)propoxy]benzyl} thiazolidine-2,4-dione (obtained in accordance with the description given in Example 3), 95 mg of N,N'-thiocarbonyldiimidazole and 5 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:1 by volume). The result of this procedure was obtained 190 mg of target compound having so pl. 53 - 58oC (softening).

Example 50. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2 - oxoacridine-3-yl)pentyloxy]-benzyl}thiazolidine-2,4-dione (Compound N 1-193)

(a) Repeating the procedure described in Example 1, except that used was 1.58 g 5-{4-[2-(5-3'-chlorphenoxamine-2 - oxoacridine-3-yl)pentyloxy the tion, listed in Obtaining 100), 2 ml triperoxonane acid and 4 ml of methylene chloride. The result of this procedure received 516 mg of target compound (so pl. 50 - 52oC) of the less polar diastereoisomer.

(b) Repeating the procedure described in Example 1, except that used 1.45 g 5-{4-[2-(5-3'-chlorphenoxamine-2 - oxoacridine-2,4-yl)pentyloxy] benzyl} -3-triphenyltetrazolium - 2,4-dione (polar isomer obtained in accordance with the description given in Obtaining 100), 2 ml triperoxonane acid and 4 ml of methylene chloride. Thus was obtained 314 mg of target compound having so pl. 53 - 55oC (from polar diastereoisomer).

Example 51. 5-{4-[2-(5-3'-Chlorphenoxamine-2-oxoacridine-3 - yl)-3-methylbutoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-195)

(a) Repeating the procedure described in Example 1, except that used 0,92 g 5-{4-[2-(5-3'-chlorphenoxamine-2 - oxoacridine-3-yl)-3-methylbutoxy]benzyl}-3-triphenyltetrazolium - 2,4-dione (less polar isomer obtained in accordance with the description given in Getting 101(a)), 2 ml triperoxonane acid and 4 ml of methylene chloride. The result of this procedure from the less polar diastereoisomer was obtained 145 mg Isklucheniem, what used 1.18 g 5-{4-[2-(5-3'-chlorphenoxamine-2 - oxoacridine-3-yl)-methylbutoxy]benzyl}-3-tryptophannutrition - 2,4-dione (polar isomer obtained in accordance with the description Receive 101 (b)), 2 ml triperoxonane acid and 4 ml of methylene chloride, resulting in a received 177 mg of target compound (so pl. 57 - 58oC) polar diastereoisomer.

Example 52. 5-{2-(5-3'-Chlorphenoxamine-2-oxoacridine-3 - yl)-2-methylpropoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-197).

To 1.5 g of a mixture of 5-{4-[2-(5-3'-chlorphenoxamine-2 - oxoacridine-3-yl)-2-methylpropoxy]benzyl}-2-aminothiazoline - 4-it and thiourea (obtained in accordance with the description given in the Receipt III) was added 4 ml of methanol and 15 ml of 6 N. aqueous solution of hydrochloric acid. The resulting mixture was heated under reflux for 5 hours After completion of heating, the reaction mixture is neutralized by adding an aqueous solution of sodium bicarbonate, and then extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. Thereafter, the ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was chromatographically on kreasindo-phase preparative liquid chromatography high resolution (YMC-pack ODS-A-trademark product, produced by YMC Co.), using as eluent a mixture of acetonitrile and water (1:1 by volume). The result of this procedure received 454 mg of target compound having so pl. 55 - 58oC.

Example 53. 5-{4-[3-(5-Phenoxymethyl-2-oxoacridine-3 - yl)propoxy]benzyl}-thiazolidine-2,4-dione (Compound N 1-49)

Repeating the procedure described in Example 1, except that used 1.98 g 5-{4-[3-(5-phenoxymethyl-2 - oxoacridine-3-yl)propoxy] benzyl} -3-triphenyltetrazolium - 2,4-dione (obtained in accordance with the description given in Getting 115), 2 ml triperoxonane acid and 4 ml of methylene chloride, which was obtained 1.18 g of the target compound, so pl. 41 - 43oC.

Example 54. 5-{4-[4-(5-3'-Chlorphenoxamine-2-oxoacridine-3 - yl)butoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-200)

Repeating the procedure described in Example 1, except that used 1.42 g 5-{4-[4-(5-3'-chlorphenoxamine-2 - oxoacridine-3-yl)butoxy] benzyl} -3-triphenyltetrazolium-2,4-dione (obtained in accordance with the description given in Getting 118), 2 ml triperoxonane acid and 4 ml of methylene chloride, resulting in a received 910 mg of the target compound, so pl. 40 - 42oC.

During the procedure, described in Example 1, except that used 1.24 g 5-{4-[2-(2-3'- chlorophenoxyacetate)propoxy]benzyl}-3-triphenyltetrazolium - 2,4-dione (obtained in accordance with the description given in Getting 122), 4 ml triperoxonane acid and 2 ml of methylene chloride, resulting in a received 181 mg of target compound having so pl. 51 - 52oC.

Example 56. 5-{4-[2-(3-7'-Phenylheptane-2 - hydroxypropylamino)propoxy]-benzyl}thiazolidine-2,4-dione (Compound N 1-204)

Repeating the procedure described in Example 2, except that used 836 mg of 3-(7-phenylheptanoic)-2-hydroxypropylamino (obtained in accordance with the description given in Getting 69), 800 mg of 5-[4-(2-oxopropoxy)-benzyl] thiazolidin-2,4-dione, 540 mg of cyanoborohydride of sodium and 50 ml of anhydrous methanol. Thus received 74 mg of the target compound with Rf= 0,21 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol 5:1 by volume).

Example 57. 5-[4-{2-[N-(3,3'-Chlorophenoxy-2-hydroxypropyl)- N-methylamino] -propoxy}benzyl]thiazolidin-2,4-dione (Compound 1-206 N)

180 mg of paraformaldehyde and 30 mg p-toluensulfonate acid was added to the following description, shown in Example 2) in 20 ml of a mixture of toluene and dioxane (1:1 by volume). The resulting mixture was heated under reflux for 3 hours then the mixture was stirred for 2 days and then was added 180 mg of paraformaldehyde and 30 mg p-toluensulfonate acid. The resulting mixture was heated for 8 hours under reflux. After this time the solvent was removed from the reaction mixture by evaporation under reduced pressure. To the resulting residue was added aqueous sodium bicarbonate solution, after which the mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. Thereafter, the ethyl acetate was removed from the extract by evaporation under reduced pressure, and the obtained residue was purified using reverse-phase preparative liquid chromatography high resolution YMC=pack ODS-A-trademark of a product manufactured by the company YMC Co.), using as eluent a mixture of acetonitrile and water (1:1 by volume). Thus was obtained 78 mg of target compound having so pl. 64 - 67oC (softening).

Example 58. 5-{4-[2-(3-4'-Phenyleneoxy-2 - hydroxypropylamino)ethoxy]benzyl}thiazolidine-2,4-dione (With whom phenyleneoxy)-2-hydroxypropylamino, 10 ml of absolute ethanol, 0.21 g of cyanoborohydride sodium and 0.52 g 5-4-(2-oksidoksi)benzyl] thiazolidin-2,4-dione. The crude product was purified by column chromatography on silica gel (eluent gradient mixture of ethyl acetate and methanol, 1: 0 to 3:1 by volume), and then purified using reverse-phase preparative liquid chromatography high resolution (column YMC-pack ODS-A-trademark), using as eluent a mixture of acetonitrile and water (3:7 - 7:13 by volume), resulting in a received 222 mg of target compound having so pl. 83 - 86oC.

Example 59. 5-{ 4-[2-(5-4'-Phenylphenoxide-2-thioxothiazolidin - 3-yl)ethoxy]benzyl}thiazolidine-2,4-dione (Compound N 1-209)

repeating the procedure described in Example 4, except that used 50 mg 5-{4-[2-(3-4 phenyleneoxy-2 - hydroxypropylamino)ethoxy] benzyl} thiazolidine-2,4-dione, 1 ml of anhydrous methylene chloride and 22 mg of N,N'-thiocarbonyldiimidazole. The crude product was purified using reverse-phase preparative liquid chromatography high resolution (YMC-pack ODS-A), using as eluent a mixture of acetonitrile and water (1: 1 - 11:9 by volume), resulting in a received 42 mg of the target compound, so pl. 68 - 70oC.oC for 3.5 hours after which time the dimethylformamide was removed from the reaction mixture by evaporation under reduced pressure. To the resulting residue was added water and the mixture was extracted with ethyl acetate. Then, the extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:4 by volume), resulting in a received 43,43 g of target compound with Rf= 0,45 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 2. 5-(3-Chlorphenoxy)-3-t-butoxycarbonyloxyimino-2-he

of 2.18 g of sodium hydride (55% dispersion in mineral oil) was washed with hexane and then added to 50 ml of dimethylformamide. To the mixture drop by drop (cooling with ice) was added a solution of 13.3 g of di-t-butylmethacrylate in 60 ml of dimethylformamide. After zi at the same temperature for one hour, and then at room temperature for 2 hours, after this time the reaction mixture was added 350 ml of dimethylformamide and 9.2 g of 3-chlorophenoxyacetate (obtained in accordance with the description given in the Receipt of 1). The resulting mixture was stirred for 2 days at room temperature and then was heated for 3 h at 70oC. after this time the reaction mixture was acidified using 2 N. aqueous solution of hydrochloric acid to pH 4, the cooling in this ice. The solvent was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was added water and then the mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. Then the ethyl acetate was removed from the extract by evaporation under reduced pressure. The obtained residue was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and hexane (1:3 to 3:1 by volume), resulting in a received 9.80 g of target compound having so pl. to 116.2 - 124,0oC.

Getting 3. 5-(3-Chlorphenoxamine)oxazolidin-2-he

To a solution of 1.97 g of 5-(3-chlorphenoxy)-3-tert-butoxycarbonyloxyimino and ice cooling was added 4 ml triperoxonane acid and the resulting mixture was stirred at room temperature for one hour. After mixing tetrahydrofuran and triperoxonane acid was removed from the reaction mixture by evaporation under reduced pressure and obtained 1.23 g of the target compound with Rf= 0,43 (thin layer chromatography on silica gel using as a developing solvent ethyl acetate).

Getting 4. Ethyl-2-[5-(3-chlorphenoxy)-2 - oxoacridine-3-yl]propionate

0.17 g of sodium hydride (55% by weight dispersion in mineral oil) was washed with hexane and then added 15 ml of dimethylformamide. To the mixture drop by drop (cooling with ice) was added a solution of 1.85 g of 5-(3-chlorphenoxamine)oxazolidin-2-it (obtained in accordance with the description given in Obtaining 3) in 10 ml of dimethylformamide. Then to this mixture was added 50 ml of dimethylformamide. After the addition the mixture was stirred at room temperature for 2 hours To the reaction mixture while cooling with ice) was added to 1.76 g of ethyl-2-bromopropionate in 5 ml of dimethylformamide and the mixture was stirred at room temperature for one hour. After this time, the dimethylformamide was removed from the reaction mixture by evaporation under reduced pressure. To the obtained residue was added is one sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:1 by volume), resulting in received of 1.05 g of the target compound with Rf= 0,38 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume).

Getting 5. 2-[5-(3-Chlorphenoxy)-2-oxoacridine-3-yl] propanol

(a) To a solution 2,95 g of ethyl 2-[5-(3-chlorphenoxy)-2-oxoacridine-3-yl] propionate (obtained in accordance with the description given in Obtaining 4) in 25 ml of tetrahydrofuran was added 0.4 g of lithium borohydride (ice cooling). To the resulting mixture were added and 0.37 ml of methanol and 5 ml of tetrahydrofuran, then the mixture was stirred at room temperature for 2 hours, the Tetrahydrofuran was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was added an aqueous solution of sodium chloride, after which the mixture was extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation with the g of the target compound, so pl. 114 - 115oC.

(b) To a solution of 152 mg of 3-(2-t-butyldimethylsilyloxy-1-methylethyl)- 5-(3-chlorphenoxamine)oxazolidin-2-it (obtained in accordance with the description given in 11( in 1 ml of anhydrous tetrahydrofuran (ice cooling) was added 1.2 ml of 26% (by weight) solution of tetrabutylammonium fluoride in tetrahydrofuran and the resulting mixture was stirred at room temperature for 1.5 hours, after this time the reaction mixture was added saturated aqueous solution of sodium chloride and the mixture was extracted with ethyl acetate. The obtained extract was dried with anhydrous sodium sulfate. Then the ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and ethanol (1:0 - 20: 1 by volume). Thus received 97 mg of the target compound, physico-chemical properties which were similar to the properties of the product obtained in accordance with the procedure described in Obtaining 5(a).

Getting 6. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2-oxoacridine-3 - yl)propoxy]benzyl}-3-triphenyltetrazolium-2,4-dione

A mixture of 344 mg tributive is piperidine was stirred at room temperature for 30 minutes To the mixture was added a solution of 500 mg of 2-[5-(3-chlorphenoxy)-2-oxoacridine-3-yl]propanol (obtained in accordance with the procedure described in Obtaining 5) in 10 ml of benzene. This mixture was stirred overnight, after which the solvent was removed from the reaction mixture by distillation under reduced pressure, and the insoluble substance was removed by filtration. The resulting filtrate evaporated to dryness under reduced pressure and the resulting residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (2:3 by volume), which was obtained 0.33 g of target compound, so pl. 90,9 - 94,0oC.

Getting 7. 2-Benzyloxycarbonylamino

To a solution of 16.9 g of DL-alanine in 100 ml of anhydrous tetrahydrofuran under ice cooling for one drop was added 31,3 ml of triethylamine. Then to the mixture was added 100 g of benzyloxycarbonylglycine (30 - 35% solution in toluene). The resulting reaction mixture was stirred at room temperature overnight. After this time, the tetrahydrofuran was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was added water. Then this mixture is sodium. Then the ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane, resulting in received 18,07 g of target compound having so pl. 52,2 - 56,6oC.

Getting 8. Benzyl N-(2-t-butyldimethylsilyloxy-1 - methylethyl)carbamate

To a mixture of 16.0 g of 2-benzyloxycarbonylamino (obtained in accordance with the description given in Obtaining 7), KZT 12.39 g of imidazole and 150 ml of dimethylformamide (ice cooling) one drop of solution was added 13,72 g t butyldimethylsilyloxy in 50 ml of dimethylformamide. The resulting mixture was stirred at room temperature for 6.5 hours after that time, the dimethylformamide was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was added water, then the mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. Then the ethyl acetate was removed from the extract by evaporation under reduced pressure. The obtained residue was purified by column chromatography on silica gel, using as the future so pl. 68,0 - 70,2oC.

9. 2-t-Butyldimethylsilyloxy-1-methylethylamine

In a mixture of 4.0 g of benzyl N-(2-t-butylmethacrylate-1-methylethyl) carbamate (obtained in accordance with the procedure described in Obtaining 8), 0,80 g of 10% palladium charcoal and 40 ml of ethanol for one hour loaded hydrogen. After this time the hydrogen was replaced with nitrogen, palladium charcoal was removed by filtration from the reaction mixture and the resulting filtrate was concentrated by evaporation under reduced pressure, resulting in a received 1.88 g of target compound with Rf= 0,27 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:3 by volume).

10. 1-(3-Chlorphenoxy)-2-(2-t - butyldimethylsilyloxy-1 methylethylamine)ethanol

A mixture of 1.48 g of 2-t-butyldimethylsilyloxy-1-methylethylamine (obtained in accordance with the description given in Obtaining 9), 1.44 g of 3-chlorophenoxyacetate (obtained in accordance with the description given in the Receipt of 1) and 16 ml of ethanol was heated under reflux for 24 hours after which time the ethanol was removed from the reaction mixture by evaporation at lower the este eluent gradient mixture of ethyl acetate and ethanol (1:0 - 10:1 by volume). The result of this procedure received 1,53 g of target compound with Rf= 0,30 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol, 10:1 by volume).

Receipt 11. 3-(2-t-Butyldimethylsilyloxy-1-methylethyl)-5- (3-chlorphenoxamine)oxazolidin-2-he

To a solution of 300 mg of 1-(3-chlorphenoxy)-2-(2-t - butyldimethylsilyloxy-1 methylethylamine)ethanol (obtained in accordance with the description given in Obtaining 10) in 5 ml of dimethylformamide was added 146 mg, N,N'-carbonyldiimidazole and the resulting mixture was stirred over night at room temperature. Then the reaction mixture was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1: 4 by volume), resulting in a received 287 mg of target compound (mixture of diastereomers), with Rf= 0,30 and 0.17 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:3 by volume).

Getting 12. 3-(3-Chlorophenoxy)-2-hydroxypropionic

To 12 ml of a solution of 0.37 g of 3-chlorophenoxyacetate (obtained in accordance with the description, poluchennuyu the mixture was stirred for 9 hours at a temperature of 50oC. after this time the solvent was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was added water and then the mixture was extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate, then the solvent was removed from the extract by evaporation under reduced pressure, resulting in a received 0.40 g of the target compound as a colorless oily substance having Rf= 0,19 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

13. 3-(3-Chlorophenoxy)-2-hydroxypropylamino

To a solution of 0.39 g of 3-(3-chlorophenoxy)-2-(hydroxypropionate (obtained in accordance with the procedure described in Obtaining 12) in 5 ml of anhydrous tetrahydrofuran in a stream of nitrogen gas while cooling with ice was gradually added to 0.19 g almoguera lithium. Under these conditions, the mixture was stirred for one and a half hours, after which the excess almoguera lithium was dissolved by adding water. Insoluble substances were removed from the reaction mixture by filtration through a layer of Celite (trademark), and the obtained filtrate was dried anhydrous Sul who was alocale 0.15 g of target compound as white crystals, so pl. 55 - 58oC.

Getting 14. 3 Phenoxy-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that he used to 1.00 g of proxymetacaine, of 1.94 g of sodium azide, 10 ml of methylformate and 45 ml of a mixture of methanol and water (8:1 by volume), resulting in received of 1.30 g of the target compound as pale yellow oily substance having Rf= 0,26 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Get 15. 3 Phenoxy-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that the used of 1.17 g of 3-phenoxy-2-hydroxypropylamino (obtained in accordance with the description given in Obtaining 14), and 0.46 g of lithium aluminum hydride and 20 ml of anhydrous tetrahydrofuran resulting received 1,09 g of target compound, so pl. 82 - 84oC.

Getting 16. 3-Phenyl-2-hydroxypropionate

Repeating the procedure in Obtaining 12, except that used 5 g ()-(2,3-epoxypropyl)benzene, 12,1 g of sodium azide, 60 ml of methylformate and 270 ml of a mixture of methanol and water (8:1 by volume), resulting in a received 6,03 g telephone silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 17. 3-Phenyl-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that used 6.0 g of 3-phenyl-2-hydroxypropionate (obtained in accordance with the description given in Obtaining 16), 2.6 g of almoguera lithium and 300 ml of anhydrous tetrahydrofuran, resulting in received 5,26 target compound, so pl. 64 - 66oC.

Getting 18. 5-[4-(2-Oxopropyl)benzyl]-thiazolidine-2,4-dione

1.28 g of sodium hydride (55 wt.% the dispersion in mineral oil) was washed with toluene and then added 30 ml of dimethylformamide. To the mixture drop by drop (cooling with ice) solution was added 3.2 g of 5-(4-mercaptobenzyl)thiazolidin-2,4-dione in 20 ml of dimethylformamide. This mixture was stirred at room temperature for 30 minutes After completion of mixing to the reaction mixture under ice cooling was added 1,69 ml bromoacetone. Then the resulting mixture was stirring at room temperature for 2 h, after which he passed during the night. The dimethylformamide was removed by evaporation under reduced pressure and the obtained residue was added water. The mixture was acidified using 1 N. aqueous solution of hydrochloric acid up until pH is not a hundred who aqueous saturated solution of sodium chloride and was dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel using as eluent ethyl acetate and hexane (2:3 by volume) and received 1.68 g of the target compound, so pl. 96-102oC.

Getting 19. 5-[4-(2,2-Diethoxyethane)benzyl]thiazolidin-2,4-dione

260 mg of sodium hydride (55 wt.% the dispersion in mineral oil) was washed with toluene and then added 5 ml of dimethylformamide. To the resulting mixture under ice cooling was added 530 mg of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione and the mixture was stirred for 30 min at room temperature. After this time the reaction mixture under ice cooling was added to 0.73 ml diethylacetanilide and the mixture was stirred for 3 hours at a temperature of 50oC. the Dimethylformamide was removed by evaporation under reduced pressure and the obtained residue was added water. This mixture was acidified using 1 N. aqueous solution of hydrochloric acid up until the pH does not become equal to a value in the range from 2 to 3, after which the mixture was extracted with ethyl acetate. Then, the extract was washed with a saturated aqueous solution of sodium chloride and was dried anhydrous sulfa is ciali using column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:2 by volume. The result of this procedure were given 600 mg of target compound with Rf= 0,46 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:2 by volume).

Getting 20. 5-[4-(2-Oksidoksi)benzyl]thiazolidin-2,4-dione

10,07 g of 5-[4-(2,2-diethoxyethane)benzyl]thiazolidin-2,4-dione (obtained in accordance with the description given in Obtaining 19) was dissolved in 80 ml of tetrahydrofuran and the resulting solution was added 20 ml of 6 N. aqueous solution of hydrochloric acid. Then the mixture was left overnight at room temperature. The solvent was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was added water and then the mixture was extracted with ethyl acetate. After that, the extract was dried with anhydrous sodium sulfate, and the ethyl acetate was removed from the extract by evaporation under reduced pressure. The obtained residue was purified by chromatography on a column of silica gel, using as eluent a mixture of ethyl acetate and hexane (2: 3 by volume), resulting in received of 5.92 g of target compound with Rf= 0,37 (finely the ATA and hexane, 2:1 by volume).

Getting 21. 2-[5-(3-Chlorphenoxy)-2-oxoacridine-3-yl]propanol

To a solution of 152 mg of 3-(2-t-butyldimethylsilyloxy-1-methylethyl)-5-(3-chlorphenoxamine) oxazolidin-2-it (obtained in accordance with the description given in Obtaining 11) in 1 ml of tetrahydrofuran drop (cooling with ice) was added 1.2 ml of 1.0 M solution of tetrabutylammonium fluoride in tetrahydrofuran. The resulting mixture was stirred at room temperature for 1.5 hours, after this time the reaction mixture was added water and sodium chloride, after which the mixture was extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate, and then ethyl acetate was removed from the extract by evaporation under reduced pressure. The obtained residue was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and ethanol (1:0 - 20:1 by volume), and received 97 mg of the target compound with Rf= 0,28 ( thin layer chromatography on silica gel using as a developing solvent ethyl acetate).

Getting 22. (S)-3-Chlorophenoxyacetic

To the mixture to 2.57 g of 3-chlorophenol, 7,86 g of triphenylphosphine and 30 ml of anhydrous benzene drop by drop we use a mixture drops added 2,01 g (R)-glycidol and the resulting mixture was left at room temperature for 14 hours After this time, the benzene was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:3 by volume). The result of this procedure received 3.11 g of target compound with Rf= 0,42 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:3 by volume).

23. (R)-2-Benzyloxycarbonylamino

To a mixture of 5.00 g D-alaninol, be 18.49 potassium carbonate, 15 ml of ethyl acetate and 15 ml of water drop was added 11,42 g benzyloxycarbonylamino. Then the resulting mixture was stirred for 1.5 hours after this time an ethyl acetate layer was separated, and the aqueous layer was extracted with ethyl acetate. After that, an ethyl acetate layer and the extract were combined, dried with anhydrous sodium sulfate, and then concentrated by evaporation under reduced pressure. The crude precipitate in the form of crystals were collected by filtration and washed with hexane, resulting in received 13,68 g of target compound, so pl. 78-80oC.

Getting 24. Benzyl N-[2-t-butultimately-silyl is hosted 12,54 g (R)-2-benzyloxycarbonylamino (obtained in accordance with the description, listed in Obtaining 23), becomes 9.97 g t butyldimethylsilyloxy, 4,90 g of imidazole and 150 ml of anhydrous dimethylformamide. Thus was obtained 16,43 g of target compound with Rf= 0,54 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 25. 2-t-Butyldimethylsilyloxy-1(R)-methylethylamine

Repeating the procedure in Obtaining 9, except that he used to 16.4 g of benzyl N-2-[t-butyldimethylsilyloxy-1(R)-methylethyl]carbamate (obtained in accordance with the procedure described in Obtaining 24), 3.5 g of 10% palladium charcoal and 100 ml of ethanol, resulting in a received 8,55 g of target compound with Rf= 0,27 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:3 by volume) and with []D= -10,1o(methanol, C = 1,155).

Getting 26. 1(S)-(3-Chlorphenoxy)-2-(2-t-butyldimethylsilyloxy-1(R)- methylethylamine)ethanol

Repeating the procedure in getting a 10, except that used 1.48 g of 2-t-butyldimethylsilyloxy-1(R)-methylethylamine (obtained in accordance with Epicureanism in Obtaining 22) and 10 ml of absolute ethanol, as a result, we got to 1.00 g of the target compound with Rf= 0,24 (thin layer chromatography on silica gel using ethyl acetate as the developing solvent) and []D= -14,3o(methanol, C=1,025).

Getting 27. 3-[2-t-Butyldimethylsilyloxy-1(R)-methylethyl] -5(S)-(3 - chlorphenoxamine)oxazolidin-2-he

Repeating the procedure in Obtaining 11, except that he used to 0.92 g 1(S)-(3-chlorphenoxy)-2-[2-t-butyldimethylsilyloxy-1(R)-methylethylamine] ethanol (obtained in accordance with the description provided in the Receiving 26), of 0.48 g of N, N'-carbonyldiimidazole and 10 ml of anhydrous dimethylformamide. Thus received to 0.92 g of target compound with Rf= 0,25 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:2 by volume) and with []D= +34,1o(methanol, C=0,960).

Getting 28. 2(R)-[5(S)-(3-Chlorphenoxy)-2-oxoacridine-3-yl] propanol

Repeating the procedure in Obtaining 5, except that used 0.88 g of 3-(2-t-butyldimethylsilyloxy-1(R)-methylsilyl)-5(S)-(3-chlorphenoxamine) oxazolidin-2-it (obtained in accordance with the description given in the on, resulting received of 0.58 g of target compound with Rf= 0,45 (thin layer chromatography on silica gel using ethyl acetate as the developing solvent) and having []D= +45,6o(methanol, C=1,000).

Getting 29. 5-{4-[2(R)-(5(S)-(3-Chlorphenoxamine-2-oxoacridine-3-yl propoxy]benzyl}-3-triphenyltetrazolium-2,4-dione

Repeating the procedure in Obtaining 6; except that used 0.52 g of 2-(R)-[5(S)-(3-chlorophenoxy-methyl)-2-oxoacridine-3-yl] propanol (obtained in accordance with the description provided in the Receiving 28), 1.01 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, of 0.44 g of tributylphosphine, 0.55 g azodicarbonamide and 30 ml of anhydrous benzene. Thus received 1,02 g of target compound with Rf= 0,26 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume) with []D= +35,9o(methanol, C = 1,000).

30. (R)-3-Chlorophenoxyacetic

Repeating the procedure in Obtaining 22, except that used 5,14 g of 3-chlorophenol, 4.44 g (S)-glycidol, 15,72 g of triphenylphosphine, 10,44 g diethylcarbamoyl cocaina chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:3 by volume).

Getting 31. (S)-2-Benzyloxycarbonyl-aminopropanol

Repeating the procedure in Obtaining 7, except that used 14,55 g L-alaninol, 126 ml 30-35% solution of benzyloxycarbonylamino in toluene, and 29.6 ml of triethylamine and 100 ml of anhydrous tetrahydrofuran, resulting in received 8,15 g of target compound, so pl. 79-80oC.

Getting 32. Benzyl N-[2-t-butultimately-silyloxy-1(S)-methylethyl]carbamate

Repeating the procedure in Obtaining 8, except that used 7,00 g (S)-2-benzyloxycarbonyl-aminopropanol (obtained in accordance with the description given in Obtaining 31), 6,03 g t butyldimethylsilyloxy, of 5.45 g of imidazole and 100 ml of anhydrous dimethylformamide, resulting in received 10,52 g of target compound with Rf= 0,48 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:7 by volume).

Getting 33.2-t-Butyldimethylsilyloxy-1(S)-methylethylamine

Repeating the procedure in Obtaining 9, except that used 10,22 g of benzyl N-[2-t-butultimately-silyloxy-1(S)-methylethyl] carbamate (obtained in accordance with the left join, with Rf= 0,27 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:3 by volume) and with []D= +9,7o(methanol, C = 1,040).

Getting 34. 1(R)-(3-Chlorphenoxy)-2-[2-t-butyldimethylsilyloxy-1(S)- methylethylamine]ethanol

Repeating the procedure in getting a 10, except that used 1.51 g of 2-t-butyldimethylsilyloxy-1(S)-methylethylamine (obtained in accordance with the description given in Obtaining 33), 0.74 g (R)-3-chlorophenoxyacetate (obtained in accordance with the description given in the Receipt of 30) and 10 ml of absolute ethanol, the result of which was obtained 0.88 g of target compound with Rf= 0,24 (thin layer chromatography on silica gel using ethyl acetate as the developing solvent) and having []D= +15,1o(methanol, C = 1,075).

Receive 35. 3-[2-t-Butyldimethylsilyloxy-1(S)-methylethyl] -5(R)-(3-chlorphenoxamine] oxazolidin-2-he

Repeating the procedure in Obtaining 11, except that used 0,82 g 1(R)-(3-chlorphenoxy)-2-[2-t-butyldimethylsilyloxy-1(S)-methylethylamine] ethanol (obtained in accordance with procedure received of 0.85 g of the target compound, with Rf= 0,25 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1: 2 by volume) and with []D= -33,4o(methanol, C = 1,040).

Getting 36. 2(S)-[5(R)-(3-Chlorphenoxy)-2-oxoacridine-3-yl] propanol

Repeating the procedure in Obtaining 5, except that he used to 0.78 g of 3-[2-t-butyldimethylsilyloxy-1(S)-methylethyl]-5(R)-(3-chlorphenoxy)- oxazolidin-2-it (obtained in accordance with the description given in Obtaining 35), of 5.85 g of a 26% solution of tetrabutylammonium fluoride in tetrahydrofuran and 10 ml of anhydrous tetrahydrofuran, resulting in received 0.52 g of target compound having so pl. 92-94oC and with []D= -47,8o(methanol, C = 0,980).

Getting 37. 5-{4-[2(S)-5[(R)-(3-chlorphenoxy)-2-oxoacridine-3-yl]propoxy] benzyl}-3-triphenyltetrazolium-2,4-dione

Repeating the procedure in Obtaining 6, except that used 0,46 g 2(S)-[5(R)-(3-chlorphenoxy)-2-oxoacridine-3-yl] propanol (obtained in accordance with the description given in Obtaining 36), of 0.90 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 0.39 g of tributylphosphine, 0,49 g ATO Rf= 0,26 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1: 1 by volume) and with []D= -35,3o(methanol, C = 1,015).

Getting 38. 1(S)-(3-Chlorphenoxy)-2-(2-t-butyldimethylsilyloxy-1(S)-methylethylamine) ethanol

Repeating the procedure in getting a 10, except that he used a 2.00 g of 2-t-butyldimethylsilyloxy-1(S)-methylethylamine, 1.92 g (S)-3-chlorophenoxyacetate (obtained in accordance with the description given in Obtaining 22) and 20 ml of ethanol, resulting in a received 2,22 g of target compound with Rf= 0,24 (thin layer chromatography on silica gel using as a developing solvent ethyl acetate) and with []D= +14,7o(methanol, C = 0,995).

Getting 39. 3-[2-t-Butyldimethylsilyloxy-1(S)-methylethyl]-5(S)-(3-chlorphenoxamine) oxazolidin-2-he

Repeating the procedure in Obtaining 11, except that he used to 2.06 g 1 (S)-(3-chlorphenoxy)-2-[2-t-butyldimethylsilyloxy-1(S)-methylethylamine] ethanol obtained according to the procedure described in Obtaining 38), 1.07 g of N,N'-carbonyldiimidazole and 20 ml of anhydrous dimethylformamide, is imagele using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume) and with []D= +51,7o(methanol, C=1,03).

Getting 40. 2(S)-[5(S)-(3-Chlorphenoxy)-2-oxoacridine-3-yl] propanol

Repeating the procedure in Obtaining 5(b), except that used a 2.00 g of 3-[2-t-butyldimethylsilyloxy-1(S)-methylethyl]-5(S)-(3-chlorphenoxamine) oxazolidin-2-it (obtained in accordance with the description given in Obtaining 39), 15 ml of a 26% solution of tetrabutylammonium fluoride in tetrahydrofuran and 20 ml of anhydrous tetrahydrofuran, resulting in received of 0.85 g of target compound having so pl. 67-70oC and with []D= +57,0o(methanol, C=1,055).

Getting 41. 5-[4-{ 2(S)-[5(S)-(3-Chlorophenoxy-methyl)-2-oxoacridine-3-yl]propoxy} benzyl]-3-triphenyltetrazolium-2,4-dione

Repeating the procedure in Obtaining 6, except that used 405 mg tributylphosphine, 25 ml of anhydrous benzene, 700 mg of 2(S)-[5-(S)-(3-chlorphenoxy)-2-oxoacridine-3-yl]propanol (obtained in accordance with the description provided in the Receiving 40), 505 mg azodicarbonamide and 745 mg of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, which was received 340 mg of the target compound, with so pl. 80-84oC and with []D
Repeating the procedure in getting a 10, except that he used to 3.00 g of 2-t-butyldimethylsilyloxy-1(R)-methylethylamine, 2,95 g (R)-3-chlorophenoxyacetate (obtained in accordance with the description given in the Receipt of 30) and 30 ml of ethanol, resulting in received of 3.73 g of target compound with Rf= 0,23 (thin layer chromatography on silica gel using ethyl acetate as the developing solvent) and having []D= -15,6o(methanol, C = 0,990).

Getting 43. 3-[2-t-butyldimethylsilyloxy-1(R)-methylethyl]-5(R)-(3-chlorphenoxy)- oxazolidin-2-he

Repeating the procedure in Obtaining 11, except that he used to 3.45 g 1(R)-(3-chlorphenoxy)-2-(2-t-butyldimethylsilyloxy-1(R)-methylethylamine) ethanol (obtained in accordance with the description given in Obtaining 42), 1.78 g of N,N'-carbonyldiimidazole and 30 ml of anhydrous dimethylformamide, resulting received to 3.52 g of target compound with Rf=0,74 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume) and with []D= -53,3o(methanol, C=1,020).

Getting 44. 2(R)-[5(R)-(3-Chloro what of, what used to 3.25 g of 3-[2-t-butyldimethylsilyloxy-1(R)-methylethyl]-5(R)-(3-chlorphenoxamine) oxazolidin-2-it (obtained in accordance with the description provided in the Receiving 43), 24 ml of a 26% solution of tetrabutylammonium fluoride in tetrahydrofuran and 30 ml of anhydrous tetrahydrofuran, resulting in received 2.28 g of target compound having so pl. 76-78oC and with []D= -65,4o(methanol, C=1,060).

Getting 45. 5-[4-{2(R)-[5(R)-(3-Chlorphenoxy)-2-oxoacridine-3-yl]propoxy} benzyl]-3-triphenyltetrazolium-2,4-dione

Repeating the procedure in Obtaining 6, except that used 526 mg tributylphosphine, 25 ml of anhydrous benzene, 900 mg of 2(R)-[5-(R)-(3-chlorphenoxy)-2-oxoacridine-3-yl]propanol (obtained in accordance with the description provided in the Receiving 44), 656 mg azodicarbonamide and to 1.21 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, which was obtained 0.65 g of the target compound, with so pl. 74-81oC and with []D= -29,0o(methanol, C=1,000).

Getting 46. Benzyloxypyridine

a 4.03 g of sodium hydride (55 wt.% the dispersion in mineral oil) was washed with hexane and then added 200 ml of anhydrous dimethylformamide. It is stirred for one hour at room temperature, then drop by drop and under ice cooling was added to 15.2 ml epibromohydrin. The resulting mixture was stirred for 1.5 h and then left overnight. After this time, the dimethylformamide was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was added water. After that, the mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. Then the ethyl acetate was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and hexane (1:6 to 1:5 by volume), resulting in received 13 g of target compound with Rf= 0,39 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:5 by volume).

Getting 47. 3-Benzyloxy-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that he used to 4.92 g of benzyloxypyrrolidine (obtained in accordance with the procedure described in Obtaining 46). 160 ml of methanol and water (8:1 by volume), 9,75 g azide is asnago substances, with Rf= 0,22 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:5 by volume).

Receive 48. 3-Benzyloxy-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that he used to 5.7 g of 3-benzyloxy-2-hydroxypropionate (obtained in accordance with the description given in Obtaining 47), of 2.09 g of lithium aluminum hydride and 250 ml of anhydrous tetrahydrofuran, resulting in a 3.5 g of target compound (so pl. 72-74oC) in the form of white crystals.

Getting 49. 5-Phenylenedimethylene

Repeating the procedure in Obtaining 46, except that used 5 g of 5-phenyl-1-pentanol, 4,99 ml epibromohydrin, 1.31 g of sodium hydride (55 wt.% the dispersion in mineral oil) and 80 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:6 by volume), resulting in received of 4.2 g of the target compound as a colorless oily substance having Rf= 0,49 (thin layer chromatography on silica gel using clintrace)-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that used 4.0 g 5-phenylenedimethylene (obtained in accordance with the description given in Obtaining 49), 5.9 g of sodium azide, 160 ml of a mixture of methanol and water (8:1 by volume) and 40 ml of methylformate, resulting received 4.5 g of the target compound as pale yellow oily substance having Rf= 0,25 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 51. 3-(5-Phenylmethoxy)-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that used 4.5 g of 3-(5-phenylmethoxy)-2-hydroxypropionate (obtained in accordance with the description provided in the Receiving 50), 1.3 g of lithium aluminum hydride and 250 ml of anhydrous tetrahydrofuran (THF), which was obtained 4.3 g of the target compound as pale yellow oily substance having Rf= 0,09 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate, ethanol and triethylamine, 10:2:1 objemu.

Getting 52. 3-Phenylpropionylamino

Poweramerica, of 2.56 g of sodium hydride (55 wt. % dispersion in mineral oil) and 100 ml of anhydrous dimethylformamide. The crude product was purified by chromatography on a column of silica gel, using as eluent a mixture of ethyl acetate and hexane (1: 6 by volume), and was obtained 7.2 g of the target compound as a colorless oily substance having Rf= 0,36 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:5 by volume).

Getting 53. 3-(3-Phenylpropoxy)-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that used 5,77 g 3-phenylpropionylamino (obtained in accordance with the description provided in the Receiving 52), of 9.75 g of sodium azide, 160 ml of a mixture of methanol and water (8:1 by volume) and 40 ml of methylformate, which was obtained 6.6 g of the target compound as pale yellow oily substance having Rf= 0,27 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:5 by volume).

Getting 54. 3-(3-Phenylpropoxy)-2-hydroxypropylamino

Repeating the procedure centuries according to the description, listed in Obtaining 53), 2.1 g of lithium aluminum hydride and 250 ml of anhydrous tetrahydrofuran, resulting in received 6 g of the target compound as pale yellow oily substance having Rf= 0,09 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate, ethanol and triethylamine, 10:2:1, by volume).

Getting 55. 2-Phenylacetylamino

Repeating the procedure in Obtaining 46, except that he used to 4.28 g of 2-phenylethanol, 1.68 g of sodium hydride (55 wt.% the dispersion in mineral oil) in 4.1 ml of epibromohydrin and 100 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of hexane and ethyl acetate (8: 1 by volume), resulting in a received 4.68 g of the target compound as a colorless oily substance having Rf= 0,77 (thin layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate, 2:1 by volume).

Getting 56. 30(2 Venlafaxi)-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except cTnI 55), to 8.20 g of sodium azide, 45 ml of methylformate and 180 ml of a mixture of methanol and water (8:1 by volume). Thus received 5.49 g of target compound in the form of a colorless substance with Rf= 0,70 (thin layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate, 2:1 by volume).

Getting 57. 3-(2-Phenylethane)-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that used 5.30 g of 3-(2-phenylethane)-2-hydroxypropionate (obtained in accordance with the description provided in the Receiving 56), 1.85 g of lithium aluminum hydride and 120 ml of anhydrous tetrahydrofuran, resulting in received 4,47 g of target compound as a colorless oily substance having Rf= 0,09 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and methanol, 10:1 by volume).

Getting 58. 4-Privatecollection

Repeating the procedure in Obtaining 46, except that he used to 5.00 g of 4-phenyl-1-butanol, 1,58 g of sodium hydride (55 wt.% the dispersion in mineral oil), 3,9 ml epibromohydrin in 110 ml of anhydrous dimethylformamide. The crude Plata and hexane (8:1 by volume), as a result, we got a 3.83 g of target compound (colorless oily substance), with Rf= 0,77 (thin layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate, 2:1 by volume).

Getting 59. 3-(4-Phenylmethoxy)-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that used 3,70 g of 4-privatecollection (obtained in accordance with the description given in Obtaining 58), of 5.83 g of sodium azide, 37 ml of methylformate and 135 ml of a mixture of methanol and water (8:1 by volume), resulting in a received 4,46 g of target compound as a colorless oily substance having Rf= 0,67 (thin layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate, 2:1 by volume).

Getting 60. 3-(4-Phenylmethoxy)-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that used 4,30 g 3-(4-phenylmethoxy)-2-hydroxypropionate (obtained in accordance with the description given in Obtaining 59), 1.31 g of lithium aluminum hydride and 120 ml of anhydrous tetrahydrofuran, resulting in received 3,70 g is graphy on silica gel using as developing solvent a mixture of ethyl acetate and methanol, 10:1 by volume).

Getting 61. 6-Phenylhexamethyleneimine

Repeating the procedure in Obtaining 46, except that used 5 g of 6-phenyl-1-hexanol, 4,6 ml epibromohydrin, of 1.23 g of sodium hydride (55 wt.% the dispersion in mineral oil) and 80 ml of anhydrous dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:7 by volume), and received 4.35 g of target compound with Rf= 0,60 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:5 by volume) as a colorless oily substance.

Getting 62. 3-(6-Phenylhexanoic)-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that used 4 g of 6-phenylhexamethyleneimine (obtained in accordance with the description given in the Receipt 61), 5.5 g of sodium azide, 100 ml of a mixture of methanol and water (8: 1 by volume) and 25 ml of methylformate, resulting received 4.5 g of the target compound as pale yellow oily substance having Rf= 0,39 (thin layer chromatography on silica the

Getting 63. 3-(6-Phenylhexanoic)-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that used 4.5 g of 3-(6-phenylhexanoic)-2-hydroxypropionate (obtained in accordance with the description provided in the Receiving 62), 1.23 g of lithium aluminum hydride and 150 ml of anhydrous tetrahydrofuran, resulting in received 3,14 g of the target compound as pale yellow oily substance with Rf= 0,12 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate, ethanol and triethylamine, 5:1:1 by volume).

Getting 64. 8-Phenylethylenediamine

Repeating the procedure in Obtaining 46, except that used 4 g 8-phenyloctanoic alcohol, 3,18 g epibromohydrin, 0.85 sodium hydride (55 wt.% the dispersion in mineral oil) and 80 ml of anhydrous dimethylformamide, resulting in received 2,42 g of target compound with Rfor = 0.51 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:6 by volume).

Receive 65. 3-(8-Phenylacrylate)-2-hydroxypropionic

Repeating the procedure described in the Doc the description, listed in Obtaining 64), 2,97 g of sodium azide, 20 ml of methylformate and 80 ml of a mixture of methanol and water (8:1 by volume), which was obtained 2.7 g of target compound with Rf= 0,29 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:5 by volume).

Getting 66. 3-(8-Phenylacrylate)-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that used 2.6 g of 3-(8-phenylacrylate)-2-hydroxypropionate (obtained in accordance with the description given in the Getting 65), 0.65 g of lithium aluminum hydride and 80 ml of anhydrous tetrahydrofuran, resulting in received 2,11 g of target compound having so pl. 50 - 54oC.

Getting 67. 7-Phenylhydroxylamine

Repeating the procedure in Obtaining 46, except that used 2 g of 7-phenylheptanoic alcohol, 1.7 ml of epibromohydrin, of 0.44 g of sodium hydride (55 wt.% the dispersion in mineral oil) and 50 ml of anhydrous dimethylformamide, resulting in received of 1.15 g of target compound with Rf= 0,49 (thin layer chromatography on silica gel using as developing solvent a mixture of atoral procedure described in Obtaining 12, except that used 1.1 g of 7-phenylhydroxylamine (obtained in accordance with the description given in Getting 67), 1.4 g of sodium azide, 15 ml of methylformate and 60 ml of a mixture of methanol and water (8:1 by volume), which was obtained 1.27 g of target compound with Rf= 0,45 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:3 by volume).

Getting 69. 3-(7-Phenylheptanoic)-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that used 1.1 g of 3-(7-phenylheptanoic)-2-hydroxypropionate (obtained in accordance with the description given in Getting 68), 0,287 g of lithium aluminum hydride and 50 ml of anhydrous tetrahydrofuran. Thus received of 0.82 g of target compound with Rf= 0,12 (thin layer chromatography on silica gel using as a developing solvent, ethyl acetate, ethanol and triethylamine, 5:1:1 by volume).

Receive 70. 3-Ftordesoxyglucose

Repeating the procedure in Obtaining 46, except that the used of 4.00 g of 3-terfenol, 1.88 g of sodium hydride (55 wt.% dispers the g of the target compound, with Rf= 0,48 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 71. 1-(3-Forfinancial)-2-(2-t-butyldimethylsilyloxy-1 methylethylamine)ethanol

Repeating the procedure in getting a 10, except that he used a 2.00 g of 2-t-butyldimethylsilyloxy-1-methylethylamine, 1,77 g 3-perfeccionamiento (obtained in accordance with the procedure described in Obtaining 70) and 20 ml of ethanol, resulting in a received 2,13 g of target compound with Rf= 0,17 (thin layer chromatography on silica gel using as a developing solvent ethyl acetate).

Getting 72. 3-(2-t-Butyldimethylsilyloxy-1-methylethyl)-5- (3-forfinancial)oxazolidin-2-he

Repeating the procedure in Obtaining 11, except that he used a 2.00 g of 1-(3-forfinancial)-2-(2-t-butyldimethylsilyloxy-1 methylethylamine)ethanol (obtained according to the procedure described in Getting 71), 20 ml of anhydrous dimethylformamide and 1.09 g of N,N'-carbonyldiimidazole, resulting received 0.74 g of target compound with Rf= 0,29 (thin-layer chromatogr is the volume) of the polar diastereoisomer. From the less polar diastereoisomer was obtained of 1.03 g of target compound with so square 54 - 58oC.

Getting 73. 2-[5-(3-Forfinancial)-oxoacridine-3-yl]propanol

Repeating the procedure in Obtaining 5(b), except that used 0,93 g 3-(2-t-butyldimethylsilyloxy-1-methylethyl)-5-(3-forfinancial) oxazolidin-2-it (obtained in accordance with the procedure described in Getting 72), 9 ml of anhydrous tetrahydrofuran and 7.2 ml of a 26% aqueous solution of tetrabutylammonium fluoride in tetrahydrofuran, resulting in received 0,63 g of target compound with Rf= 0,18 (thin layer chromatography on silica gel using ethyl acetate as the developing solvent).

Getting 74. 5-{ 4-[2-(5-3'-Forfinancial-2-oxoacridine-3-yl)propoxy]benzyl}-3-triphenyltetrazolium-2,4-dione

Repeating the procedure in Obtaining 6, except that used 364 mg tributylphosphine, 5 ml of anhydrous benzene, 698 mg of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 454 mg of azodicarbonamide and 489 mg of 2-[5-(3-forfinancial)-2-oxoacridine-3-yl]propanol (obtained in accordance with the description given in Getting 73), resulting in perfectly is telelinks-1 methylethylamine-ethanol

Repeating the procedure in getting a 10, except that used up 3.22 g of 2-t-butyldimethylsilyloxy-1 - methylethylamine, 3.00 g of 4-methoxytrimethylsilane and 30 ml of ethanol, resulting in a received 3.58 g of target compound with Rf= 0,15 (thin layer chromatography on silica gel using ethyl acetate as the developing solvent).

Getting 76. 3-(2-t-Butyldimethylsilyloxy-1-methylethyl)-5- (4-methoxyphenoxy-methyl)oxazolidin-2-he

Repeating the procedure in Obtaining 11, except that he used to 3.36 g of 1-(4-methoxyphenoxy)-2-(2-t - butyldimethylsilyloxy-1 methylethylamine)ethanol (obtained in accordance with the description given in Obtaining 75), 1.78 g of N,N'-carbonyldiimidazole and 30 ml of anhydrous dimethylformamide. Thus from the polar diastereoisomer was obtained 1.42 g of target compound with Rf= 0,41 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:2 by volume), and the less polar diastereoisomer was obtained of 1.62 g of target compound having so pl. 81-85oC.

Getting 77. 2-[5-(4-Methoxyphenoxy)-2-oxoacridine-3 - yl]propane is dimethylsiloxy-1-methylethyl)-5-(4-methoxyphenoxy) oxazolidin-2-it (less polar diastereoisomer, obtained in accordance with the description given in Getting 76), 12 ml of tetrabutylammonium fluoride (26% solution in tetrahydrofuran) and 10 ml of anhydrous tetrahydrofuran, resulting in received 1.20 g of target compound having so pl. 80-88oC (less polar diastereoisomer).

(b) Repeating the procedure in Obtaining 5(b), except that used 1.26 g of 3-(2-t-butyldimethylsilyloxy-1-methylethyl)-5-(4-methoxyphenoxy) oxazolidin-2,4-she (polar isomer obtained in accordance with the description given in Getting 76), and 9.6 ml of a 26% aqueous solution of tetrabutylammonium fluoride in tetrahydrofuran and 10 ml of anhydrous tetrahydrofuran. Thus from the polar diastereoisomer was obtained 0,86 g of target compound, so pl. 62-67oC.

Getting 78. 5-{4-[2-(5-4'-Methoxyphenoxy-2 - oxoacridine-3-yl)propoxy]-benzyl}-3-triphenyltetrazolium - 2,4-dione

(a) Repeating the procedure in Obtaining 6, except that used 800 mg of 2-[5-(4-methoxyphenoxy)-2 - oxoacridine-3-yl]propanol (less polar isomer obtained in accordance with the description given in Getting 77(a)), 688 mg tributylphosphine, 30 ml of anhydrous benzene, 1.30 grams of 5-(4-hydroxyp the second diastereoisomer was obtained 0.75 g of target compound with so pl. 60-66oC.

(b) Repeating the procedure in Obtaining 6, except that he used to 0.85 g of 2-[5-(4-methoxyphenoxy)-2 - oxoacridine-3-yl] propanol (polar isomer obtained in accordance with the description given in Getting 77(b)), 0.73 g of tributylphosphine, 50 ml of anhydrous benzene, 1.68 g of 5-(4 - hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione and of 0.91 g azodicarbonamide, the result was received with 0.93 g of target compound (so pl. 85-94oC) of the polar diastereoisomer.

Getting 79. 3-Dimethylaminopropylamine

Repeating the procedure in Obtaining 46, except that the used of 4.00 g of 3-dimethylaminophenol, and 4.5 ml of epibromohydrin, 153 g of sodium hydride (55 wt.% the dispersion in mineral oil) and 50 ml of dimethylformamide. The crude product was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1: 4 by volume), resulting in a received 4,18 g of target compound with Rf= 0,36 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

80. 3-(3-Dimethylaminophenol is ovali 2.0 g 3-dimethylaminopropylamine (obtained in accordance with the description, listed in Obtaining 79), 3.25 g of sodium azide, 20 ml of methylformate and 90 ml of a mixture of methanol and water (8:1 by volume), resulting in received of 2.34 g of target compound with Rf= 0,35 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 81. 3-(3-Dimethylaminopropoxy)-2 - hydroxypropylamino

Repeating the procedure in Obtaining 13, except that he used to 2.41 g of 3-(3-dimethylaminopropoxy)-2 - hydroxypropylamino (obtained in accordance with the description given in Obtaining 80), 0,76 g of lithium aluminum hydride and 50 ml of anhydrous tetrahydrofuran, resulting in received of 1.80 g of target compound with Rf= 0,9 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol, 4:1 by volume).

Getting 82. 4-Phenyleneoxymethylene

Repeating the procedure in Obtaining 46, except that the used of 4.00 g of 4-phenylphenol, of 3.97 g of epibromohydrin, 1.27 g of sodium hydride (55 wt. % dispersion in mineral oil) and 80 ml of anhydrous dimethylformamide, resulting in received 4,43 g target spectoral procedure described in Obtaining 12, except that he used to 3.00 g of 4-phenyleneoxymethylene (obtained in accordance with the procedure described in getting 82), to 4.23 g of sodium azide, 15 ml of methylformate and 90 ml of a mixture of methanol and water (8:1 by volume), which was awarded to 3.09 g of target compound having so pl. 72,2 - 73,9oC.

Getting 84. 3-(4-Phenyleneoxy)-2-hydroxypropylamino

The mixture 2,94 g 3-(4-phenyleneoxy)-2-hydroxypropionate (obtained in accordance with the description given in Getting 83), 0.3 g of 10% palladium charcoal and 60 ml of ethanol for 3 h were injected hydrogen. Then insoluble substances were removed by filtration and the resulting filtrate was concentrated by evaporation under reduced pressure, resulting in a received 2,84 g of target compound, so pl. 137,7-146,8oC.

Getting 85. Phenyldimethylsilane

To a mixture of 6 ml of epibromohydrin, of 5.45 g of sodium hydroxide and 30 ml of 1,4-dioxane drop and at room temperature was added a solution of 5.0 g of thiophenol in 30 ml of 1,4-dioxane and the resulting mixture was stirred at room temperature for 36 hours after this time the insoluble solids were removed by filtration, and 1,4-dioxane is evaporated from the filtrate and the Ali aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. Thereafter, the ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (1:10 by volume). The result of this procedure was given to 6.78 g of target compound as a colorless oily substance having Rf= 0,60 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:10 by volume).

Getting 86. 3 Phenylthio-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that used 7.2 g of phenyldimethylsilane (obtained in accordance with the description given in Getting 85), 14 g of sodium azide, 65 ml of methylformate and 270 ml of a mixture of methanol and water (8:1 by volume), which was received with 8.33 g of target compound (colorless oily substance) with Rf= 0,23 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:10 by volume).

Getting 87. 3 Phenylthio-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except tog is Getting 86), 2.9 g of lithium aluminum hydride and 400 ml of anhydrous tetrahydrofuran (THF), which was obtained 6.8 g of target compound, so pl. 57 - 61oC.

Getting 88. N-Methyl-N-phenylaminopyrimidine

Repeating the procedure in Obtaining 46, except that used 5 g of N-methylaniline, 7.65 ml of epibromohydrin, 2,44 g of sodium hydride (55 wt. % dispersion in mineral oil) and 100 ml of anhydrous dimethylformamide, resulting in received 1,67 g of the target compound as pale yellow oily substance having Rf= 0,33 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:10 by volume).

Getting 89. 3-(N-Methyl-N-phenylamino)-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that the used of 1.65 g of N-methyl-N-phenylaminopyrimidine (obtained in accordance with the description given in Getting 88), 3,29 g of sodium azide, 15 ml of methylformate and 63 ml of a mixture of methanol and water (8:1 by volume), which was obtained 1.9 g of the target compound as pale yellow oily substance having Rf= 0,09 (thin layer chromatography on silica gel using the Il-N-phenylamino)-2-hydroxypropylamino

In a mixture of 1.85 g of 3-(N-methyl-N-phenylamino)-2-hydroxypropionate (obtained in accordance with the procedure described in Getting 89), 0.9 g of 10% palladium on coal and 30 ml of ethanol for 1.5 h were injected hydrogen. After this time the hydrogen was replaced with nitrogen and palladium on coal from the reaction mixture were removed by filtration. The filtrate was concentrated by evaporation under reduced pressure and obtained 1.6 g of target compound with so pl. 136oC (decomposition).

Getting 91. 3-Chlorobenzylchloride

Repeating the procedure in Obtaining 46, except that he used to 5.00 g of 3-chlorobenzylamino alcohol and 1.83 g of sodium hydride (55 wt. % dispersion in mineral oil) of 3.45 ml epibromohydrin and 60 ml of anhydrous dimethylformamide, resulting in received of 5.45 g of target compound with Rf= 0,31 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:6 by volume).

Getting 92. 3-(3-Chlorobenzoyloxy)-2-hydroxypropionic

Repeating the procedure in Obtaining 12, except that he used to 4.73 g of 3-chlorobenzylidenemalononitrile (obtained in accordance with the description, privatednsname which received a grade of 5.74 g of the target compound, with Rf= 0,29 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 93. 3-(3-Chlorobenzoyloxy)-2-hydroxypropylamino

Repeating the procedure in Obtaining 13, except that he used to 6.22 g of 3-(3-chlorobenzoyloxy)-2-hydroxypropionate (obtained in accordance with the description given in Getting 92), of 1.97 g of lithium aluminum hydride and 120 ml of anhydrous tetrahydrofuran, resulting in received 3,37 g of target compound with Rf= 0,03 (thin layer chromatography on silica gel using as a developing solvent ethyl acetate).

Getting 94. 5-[4-(2-Oxobutanoic)benzyl]-3 - triphenyltetrazolium-2,4-dione

The mixture 7,37 ml of 1-bromo-2-butanone, of 20.0 g of 5-(4-hydroxybenzyl)-3 - triphenyltetrazolium-2,4-dione, 21,18 g of cesium carbonate and 200 ml of anhydrous acetone was stirred for 3 h at room temperature. Then the acetone was removed by evaporation under reduced pressure, resulting in the obtained residue. To this residue was added water and the mixture was extracted with ethyl acetate. After that, the extract was washed with an aqueous solution of sodium chloride, and then obrazovavshijsya the residue was recrystallized from a mixture of ethyl acetate, diethyl ether and diisopropyl ether, resulting in the received 19,36 g of target compound, so pl. 155, 2mm - 156,4oC.

Getting 95. 5-[4-(2-Oxobutanoic)benzyl]-thiazolidine-2,4-dione

To a solution of 19.3 g of 5-[4-(2-oxobutanoic)benzyl]-3-triphenyltetrazolium-2,4-dione (obtained in accordance with the description given in Getting 94) in 100 ml of methylene chloride was added 50 ml triperoxonane acid. The resulting mixture was stirred at room temperature for one and a half hours. After concentration by evaporation under reduced pressure, the obtained residue. To this residue was added water and the resulting mixture was neutralized by adding sodium bicarbonate, and then extracted with ethyl acetate. After that, the extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. The ethyl acetate was removed by evaporation under reduced pressure and the obtained residue was chromatographically on a column of silica gel, using as eluent a mixture of ethyl acetate and hexane (1:2 by volume). After recrystallization from a mixture of ethyl acetate and diisopropyl ether were received of 9.55 g of target compound having so pl. 141,5 - to 145.7oC.

Getting 96. Ethyl 2-[5-(3-Chlorphenoxamine used 1.35 g of sodium hydride (55 wt.% the dispersion in mineral oil), 6,00 g of 5-(chlorphenoxamine)oxazolidin-2-it, 100 ml of anhydrous dimethylformamide and 6,48 g of ethyl 2-bromovalerate. The crude product was chromatographically on a column of silica gel, using as eluent a mixture of ethyl acetate and hexane (1:3 by volume). The result of this procedure were obtained separately polar diastereoisomer and less polar diastereoisomer. Thus from the polar diastereoisomer was obtained 4.5 g of target compound with Rf= 0,58 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume). From the less polar diastereoisomer was obtained 4,47 g of target compound with so pl. 43 - 49oC.

Getting 97. 2-[5-(3-Chlorphenoxy)-2-oxoacridine-3-yl]pentanal

(a) Repeating the procedure in Obtaining 5, except that he used to 4.38 g of ethyl 2-[5-(3-chlorphenoxy)-2-oxoacridine-3-yl] pentanoate (less polar isomer obtained in accordance with the procedure described in Getting 96), 40 ml of anhydrous tetrahydrofuran (THF, 0.39 g of lithium borohydride and 0.29 grams of anhydrous methanol, resulting from the less polar isomer was obtained 2,22 g of target compound having so pl. 79 - 81oC.

oC.

Getting 98. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2-oxoacridine-3-yl)pentyloxy]benzyl}-3-triphenyltetrazolium-2,4-dione

(a) Repeating the procedure in Obtaining 6, except that he used to 1.00 g of 2-[5-(3-chlorphenoxy)-2-oxoacridine-3-yl] pentanal (less polar isomer obtained in accordance with the description given in Getting 97(a)), 1.07 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 0.74 g of triphenylphosphine, 0,49 g diethylazodicarboxylate and 30 ml of anhydrous tetrahydrofuran, as a result of the less polar diastereoisomer was obtained 1,58 g of target compound with Rfor = 0.6 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume).

(b) Repeating the procedure in Obtaining 6, except that he used to 1.00 g of 2-[5-(3-chlorphenoxy)-2 - oxoacridine-3-yl] pentanal (polar isomer, poluchennogo the-dione, 0.73 g of triphenylphosphine, 30 ml of anhydrous tetrahydrofuran and 0.49 g of diethylazodicarboxylate, resulting from the polar diastereoisomer was obtained 1.22 g of target compound with Rf= 0,57 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume).

Getting 99. Methyl 2-[5-(3-chlorphenoxy)-2 - oxoacridine-3-yl] -3-methylbutanoate

Repeating the procedure in Obtaining 4, except that he used to 0.92 g of sodium hydride (55 wt.% the dispersion in mineral oil), 80 ml of anhydrous dimethylformamide, 4,10 g (5-(3-chlorphenoxamine)oxazolidin-2-it 4,16 g of methyl 2-bromoisobutyrate, resulting in the obtained crude product. This crude product was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and hexane (1:3 to 1:2 by volume). Thus from the polar diastereoisomer was obtained of 1.05 g of the target compound with Rf= 0,39 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume), and the less polar diastereoisomer was obtained of 1.23 g of the target of the is its solvent mixture of ethyl acetate and hexane, 1:1 by volume).

Getting 100. 2-[5-(3-Chlorphenoxy)-2-oxoacridine - 3-yl] methylbutanol

(a) Repeating the procedure in Obtaining 5, except that he used to 1.14 g of methyl 2-[5-(3-chlorphenoxy)-2 - oxoacridine-3-yl]-3-methylbutanoate (less polar isomer obtained in accordance with the description given in Getting 99), 144 mg of lithium borohydride, 12 ml of anhydrous DMF (dimethylformamide) and 105 mg of anhydrous methanol, resulting in a received 1,02 g of target compound with Rf= 0,26 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume) of the less polar diastereoisomer.

(b) Repeating the procedure in Obtaining 5, except that used 0,93 g of methyl 2-[5-(3-chlorphenoxy)-2 - oxoacridine-3-yl] -3-methylbutanoate (polar isomer obtained in accordance with the description given in Getting 99), 118 g of lithium borohydride, 10 ml of anhydrous tetrahydrofuran and 87 mg of anhydrous methanol, resulting from the polar diastereoisomer was obtained of 0.47 g of target compound with Rf= 0,48 (thin layer chromatography on silica gel using quality shall organochemical-2-oxoacridine - 3-yl)-3-methylbutoxy]benzyl}-3-triphenyltetrazolium-2,4-dione

(a) Repeating the procedure in Obtaining 6, except that used 800 mg of 2-[5-(3-chlorphenoxy)-2 - oxoacridine-3-yl] -3-methylbutanol (less polar isomer obtained in accordance with the description given in Obtaining 100(a)), 656 mg of triphenylphosphine, 20 ml of anhydrous tetrahydrofuran, 791 mg of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione and 435 mg of diethylazodicarboxylate. Thus, from the less polar diastereoisomer was obtained 0,92 g of target compound, so pl. 60-66oC.

(b) Repeating the procedure in Obtaining 6, except that the used of 0.90 g of 2-[5-(3-chlorphenoxy)-2-oxoacridine-3-yl]-3-methylbutanol (polar isomer obtained in accordance with the description given in Obtaining 100(b)), 0,76 g of triphenylphosphine, 0.88 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 20 ml of anhydrous tetrahydrofuran and 0.49 g of diethylazodicarboxylate. The result of this procedure from the polar diastereoisomer was obtained 1.22 g of target compound with Rf= 0,55 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:1 by volume).

Getting 102. 2-Benzyloxycarbonyl and of 7.00 g of 2-amino-2-methylpropanol, 13,47 g benzyloxycarbonylamino, 13,13 g of potassium carbonate in 35 ml of ethyl acetate and 35 ml of water. Thus received 17,59 g of target compound with Rf= 0,72 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 3:1 by volume).

Example 103. Gasoline N-(2-t-butultimately-silyloxy-1,1 - dimethylethyl)carbamate

Repeating the procedure in Obtaining 8, except that used 10,00 g 2 benzyloxycarbonylamino-2 - methylpropanol, 7,35 g of imidazole, 150 ml of anhydrous dimethylformamide and 8,14 g t butyldimethylsilyloxy, resulting received 14,68 g of target compound with Rf= 0,73 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 104. 2-t-Butyldimethylsilyloxy-1,1-dimethylethylamine

Repeating the procedure in Obtaining 9, except that the used of 8.00 g of benzyl N-[2-t-butyldimethylsilyloxy - 1,1-dimethylethyl]carbamate (obtained in accordance with the description given in Getting 103), 1,60 g 10% palladium on coal and 80 ml of ethanol, resulting received was 4.02 g of the target sedimentate).

Getting 105. 1-(3-Chlorphenoxy)-2-(2-t - butyldimethylsilyloxy-1,1-dimethylethylamine)ethanol

Repeating the procedure in getting a 10, except that he used to 3.36 g of 2-t-butyldimethylsilyloxy-1,1 - dimethylethylamine, 3,05 g 3-chlorophenoxyacetate and 30 ml of ethanol, resulting in received of 4.54 g of the target compound, so pl. 70,5-77,3oC.

Getting 106. 3-(2-t-Butyldimethylsilyloxy-1,1-dimethylethyl)-5- (3-chlorphenoxamine)oxazolidin-2-he

Repeating the procedure in Obtaining 11, except that he used to 5.13 g of 1-(3-chlorphenoxy)-2-(2-t-butyldimethylsilyloxy-1,1-dimethylethylamine)ethanol (obtained in accordance with the description given in Getting 105), 50 ml of anhydrous dimethylformamide and at 2.59 g of N, N'-carbonyldiimidazole. Thus was obtained at 5.27 g of target compound with Rf= 0,33 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 1:4 by volume).

Getting 107. 5-(3-Chlorphenoxy)-3-(2-hydroxy-1,1 - dimethylethyl)-oxazolidin-2-he

To a solution of 3.84 g of 3-(2-t-butyldimethylsilyloxy-1,1-dimethylethyl)- 5-(3-chlorphenoxamine)oxazolidin-2-it (obtained in accordance with the laws of the Sabbath. doroda in acetonitrile. The resulting mixture was stirred at room temperature for one hour. Then the solvent was removed from the reaction mixture by evaporation under reduced pressure, resulting received a 2.71 g of the target compound, so pl. 81-82oC.

Getting 108. 5-(3-Chlorphenoxy)-3-[2-(4-nitrophenoxy)-1,1 - dimethylethyl]-oxazolidin-2-he

To a solution of 200 mg of 5-(3-chlorphenoxy)-3-(2-hydroxy-1,1 - dimethylethyl)oxazolidin-2-she and 288 mg of 4-peritrabecular in 5 ml of dimethylformamide under ice cooling with three portions was added 35 mg of sodium hydride (55 wt.% the dispersion in mineral oil). The resulting mixture was stirred at the same temperature for 30 minutes and Then the mixture was stirred at room temperature for 7 h and the solvent was removed from the reaction mixture by evaporation under reduced pressure. To the obtained residue was added water and the mixture was extracted with ethyl acetate. Then, the extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure, then the residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (2:3 the value of 109. 3-[2-(4-Aminophenoxy)-1,1-dimethylethyl]-5- (3-chlorphenoxamine)oxazolidin-2-he

To a solution of 2.34 g of 5-(3-chlorphenoxy)-3-[2-(4-nitrophenoxy)- 1,1-dimethylethyl]oxazolidin-2-it (obtained in accordance with the description given in Getting 108) in 70 ml of a mixture of ethyl acetate and t-butanol (9:1 by volume) was added 6,32 g dihydrate chloride tin (2). To the resulting mixture at a temperature of 66oC in an oil bath was added 0.11 g sodium borohydride. Then the mixture was stirred at the same temperature for 6 hours, after this time the solvent was removed from the reaction mixture by evaporation under reduced pressure, resulting in the formation of residue. This residue was neutralized by adding aqueous sodium bicarbonate solution. The precipitated insoluble matter was removed by filtration and the resulting filtrate was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. Thereafter, the ethyl acetate was removed from the extract by evaporation under reduced pressure, resulting received a 1.96 g of target compound with Rf= 0,34 (thin layer chromatography on silica gel using as developing solvent a mixture of tolidin-3-yl)-2-methylpropoxy]phenyl}propionate

To a solution of 2.20 g of 3-[2-(4-aminophenoxy)-1,1-dimethylethyl]-5- (3-chlorphenoxamine)oxazolidin-2-it in 25 ml of acetone drop (cooling with ice) was added 4,82 g of 47% aqueous solution of Pomodoro, and then to the mixture was added 2 ml of an aqueous solution of 462 mg of sodium nitrite. The resulting mixture was stirred at the same temperature for 15 min and then at room temperature was added 7,18 g of butyl acrylate and 157 mg of copper oxide (1). The resulting mixture was stirred at room temperature for 2.5 hours the Solvent was removed from the reaction mixture by evaporation under reduced pressure, the resulting residue was neutralized by adding aqueous sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure, resulting in the obtained residue. This residue was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and hexane (1:3 to 1:1 by volume), resulting in a received 2.24 g of target compound with Rf= 0,44 (thin layer chromatography on silica>/P>Getting 111. 5-{ 4-[2-(5-3'-Chlorphenoxamine-2-oxoacridine - 3-yl)-2-methylpropoxy]benzyl}-2-aminothiazoline-4-one

To a solution 2,07 g of butyl 2-bromo-3-{4-[2-(5-3'-chlorphenoxamine-2 - oxoacridine-3-yl)-2-methylpropoxy] phenyl} propionate (obtained in accordance with the description given in Obtaining 110) in 30 ml of methanol was added 0.5 g of thiourea. To the mixture was added 0,49 g of sodium acetate. Then the obtained mixture was heated under reflux for 5 h, after which the solvent was removed from the reaction mixture by evaporation under reduced pressure. To the obtained residue was added a saturated aqueous solution of sodium chloride and the mixture was extracted with ethyl acetate. The extract was dried with anhydrous sodium sulfate, and the ethyl acetate was removed by evaporation under reduced pressure. The obtained residue was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and tetrahydrofuran (1: 0 to 3:1 by volume). The result of this procedure received 1.50 g of the mixture of target compound (Rf= 0,19, thin-layer chromatography on silica gel using as a developing solvent of ethyl acetate and thiourea.

Getting 112. 5-Phenoxyl the amide under ice cooling was added 422 mg of N,N'-carbonyldiimidazole. The resulting mixture was stirred at room temperature overnight. After this time the solvent was removed from the reaction mixture by evaporation under reduced pressure and the obtained concentrate was added water. Then the mixture was extracted with ethyl acetate and the extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure, resulting in the obtained residue. This residue was purified by column chromatography on silica gel (eluent - ethyl acetate) and got 490 mg of the target compound, so pl. 110-111oC.

Getting 113. Ethyl 3-(5-phenoxymethyl-2-oxoacridine-3-yl)propionate.

Repeating the procedure in Obtaining 4, except that used 113 mg of sodium hydride (55 wt.% the dispersion in mineral oil) in 10 ml of anhydrous dimethylformamide, 420 mg of 5-phenoxymethylpenicillin-2-it (obtained in accordance with the description given in Getting 112) and 471 mg of ethyl 3-bromopropionate. Thus was obtained 463 mg of the target compound with Rf= 0,34 (thin layer chromatography on silica gel using as manifesting RASTVORITELYa.

Repeating the procedure in Obtaining 5(a), except that used 1.64 g of ethyl 3-(5-phenoxymethyl-2-oxoacridine-3-yl)propionate (obtained in accordance with the procedure described in Getting 113), 15 ml of anhydrous tetrahydrofuran, 244 mg of lithium borohydride and 179 ml of anhydrous methanol, resulting in received of 1.41 g of target compound with Rf= 0,28 (thin layer chromatography on silica gel using ethyl acetate as the developing solvent).

Getting 115. 5-{4-[3-(5-Phenoxymethyl-2-oxoacridine-3 - yl)propoxy] -benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating the procedure in Obtaining 6, except that used 1.29 g of tributylphosphine, 30 ml of anhydrous benzene, 2,98 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 1,61 g azodicarbonamide and of 1.33 g of 3-(5-phenoxymethyl-2-oxoacridine-3-yl)propanol (obtained in accordance with the description given in the Receipt 114). Thus received 2,04 g of target compound, so pl. 70-73oC.

Getting 116. Ethyl 4-[5-(3-Chlorphenoxy)-2 - oxoacridine-3-yl] butyrate

Repeating the procedure in Obtaining 4, except that he used oxymethyl)oxazolidin-2-she was 2.34 g of ethyl 4-bromobutyrate. Thus received 1.50 g of target compound with Rf= 0,39 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 2:1 by volume).

Getting 117. Ethyl 4-[5-(3-Chlorphenoxy)-2 - oxoacridine-3-yl] butanol

Repeating the procedure in Obtaining 5, except that used was 1.43 g of ethyl 4-[5-(3-chlorphenoxy)-2 - oxoacridine-3-yl] butyrate (obtained in accordance with the description given in Getting 116), 183 mg sodium borohydride, 20 ml of anhydrous tetrahydrofuran and 135 ml of anhydrous methanol. The result of this procedure was obtained 1.26 g of target compound with Rf= 0,31 (thin layer chromatography on silica gel using as a developing solvent ethyl acetate).

Getting 118. 5-{ 4-[4-(5-3'-Chlorphenoxamine-2-oxoacridine - 3-yl)butoxy]-benzyl}-3-triphenyltetrazolium-2,4-dione

Repeating the procedure in Obtaining 6, except that used 647 mg tributylphosphine, 20 ml of anhydrous benzene, 1,49 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 807 mg azodicarbonamide and 800 mg of 4-[5-(3-chlorphenoxy)-2-oxoacridine received 1,49 g of target compound, so pl. 68-72oC.

Getting 119. 2 Chloroacetamido-1-(3-chlorphenoxamine)ethanol

To a solution of 300 mg of 3-(3-chlorophenoxy)-2-hydroxypropylamino in 4 ml of anhydrous tetrahydrofuran under ice cooling was added a solution of 0.24 ml of triethylamine in 1 ml of anhydrous tetrahydrofuran. Then to the resulting reaction mixture drop by drop) was added 1 ml of a solution of 192 mg of chloroacetanilide in anhydrous tetrahydrofuran. After the reaction mixture was stirred for 3 h at room temperature. After this time the solvent was removed from the reaction mixture by evaporation under reduced pressure and the obtained residue. To this residue was added water, then the mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride, and then dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a mixture of ethyl acetate and hexane (3:2 by volume). The result of this procedure were obtained 310 mg of target compound having so pl. 74-77oC.

Getting 120. Ethyl 2-[6-(3-chlorphenoxy)-3-exmortis-4-yl]propionate

To the RIRs>oC in an oil bath drop was added a solution of 5.50 g of 2-chloroacetamido-1-(3-chlorphenoxamine)ethanol (obtained in accordance with the description given in Getting 119) in 110 ml of dimethylformamide. Thereafter, the resulting reaction mixture was stirred at the same temperature for one hour. Then to the reaction mixture drop by drop and under ice cooling was added a 5.25 g of ethyl 2-bromopropionate and the mixture was stirred for one day. After this time the solvent was removed from the reaction mixture by evaporation under reduced pressure, resulting in the obtained residue. To this residue was added water and the mixture was extracted with ethyl acetate. Then, the extract was washed with an aqueous solution of sodium chloride and was dried with anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure and the obtained residue was purified by column chromatography on silica gel, using as eluent a gradient mixture of ethyl acetate and hexane (1:2 to 3:2 by volume). The result of this procedure was given to 4.23 g of target compound with Rf= 0,39 (thin layer chromatography using as a developing solvent ethyl acetate).

Getting 121. 2-[2-(3-Harfe what about the drop and with ice cooling was added a solution of 1.50 g of ethyl 2-[6-(3-chlorphenoxy)-3-exmortis-4-yl] propionate in 10 ml of anhydrous tetrahydrofuran. The resulting mixture was stirred at room temperature for 2.5 h, after which the excess lithium aluminum hydride was decomposed by adding to the mixture of decahydrate sodium sulfate. Insoluble substances were removed from the reaction mixture using accelerator filtration (CeliteR, trade mark), after which the solvent was removed from the filtrate by evaporation under reduced pressure, resulting in a received 0.97 g of target compound with Rf= 0,19 (thin layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane, 3:1 by volume).

Getting 122. 5-{4-[2-(2-3'-Chlorophenoxyacetate) propoxy]benzyl} -3-triphenyltetrazolium-2,4-dione

Repeating the procedure in Obtaining 6, except that he used to 1.21 g of triphenylphosphine, 20 ml of anhydrous tetrahydrofuran, is 1.77 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 0,81 g diethylazodicarboxylate and of 1.32 g of 2-[2-(3-chlorphenoxamine)morpholino] propanol (obtained in accordance with the procedure described in Getting 121). Thus received 1.32 g of target compound having so pl. 48-53oC.

Additional biological data (Hyperlipemic is of lipids in the serum. Accordingly, the degree of hyperlipemia can be estimated by measuring the amount of triglyceride in the blood.

The experimental animals were male F344 rats. Each animal group contained 5 animals, and animals used for experiments when they reached the age of 7 weeks. Each test was given orally with the test compound mixed with a carrier (of 0.5% CMC), 50 mg/mg/day for 2 weeks. At the same time another group of 5 animals (control group) was given orally only media. After the introduction of rats investigated the funds within 2 weeks of each rat took the blood. Serum was separated and measured the level of triglycerides using an automatic analyzer (type 736 manufactured by Hitachi Ltd.). The results are summarized in table. 10.

As you can see from the above table. 10 results, the compounds of the invention showed a decrease in the level of triglyceride.

1 1. Derivatives of thiazolidine formula I 6 1 in which R1and R2are the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms; 4 R3is a hydrogen atom; 4 a and b are the same or which together represent a group of the formula 6 or-CH2CH2-; 4, X is a group of the formula 6 W - (CH2)m- X1-, 1 in which W is a phenyl group which is unsubstituted or substituted by at least one Deputy, selected from alkyl groups having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, halogen atom, phenyl groups and groups of the formula 6-NRaRb, 1 in which Raand Rbare the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms; 4 X1is a single bond, an oxygen atom, a sulfur atom or a group of the formula >> NR4in which R4is an alkyl group having 1 to 8 carbon atoms; 4 m is 0 or an integer from 1 to 8; 4 Y is a group of the formula 6 -(CH2)n- Y1- 1 in which Y1is an oxygen atom or a sulfur atom; 4 n is an integer from 1 to 5; 4 z group of formula i 6 1 in which R5is a hydrogen atom, 1, and their salts. 2 2. Derived thiazolidine under item 1, in which R1and R2are the same or different and each represents a hydrogen atom or alkyl group having 1 to 6 carbon atoms. 2 3. Derived thiazolidine under item 1, in which a and b are the same or different and each pre is the formula 6 or-CH2CH2-. 2 4. Derived thiazolidine under item 1, in which X represents a group of the formula 6 W - (CH2)m- X1-, 1 in which W is a phenyl group which is unsubstituted or substituted by 1 to 3 substituents, selected from alkyl groups having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, halogen atoms, phenyl groups and groups of the formula 6-NRaRb, 1 in which Raand Rbare the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms; 4 X1is a single bond, an oxygen atom, a sulfur atom or a group of the formula 6-N (R4)-, 1 in which R4is an alkyl group having 1 to 4 carbon atoms; 4 m is 0 or an integer from 1 to 8. 2 5. Derived thiazolidine under item 1, in which R1and R2are the same or different and each represents a hydrogen atom or alkyl group having 1 to 6 carbon atoms; 4 a and b are the same or different and each represents a hydrogen atom or alkyl group having from 1 to 4 carbon atoms, or a or b together form a group of the formula 6 or-CH2CH2-; 4, X is a group of the formula 6 W - (CH2)m- X1-, 1 is killnig groups, having 1 to 4 carbon atoms, alkoxygroup having 1 to 4 carbon atoms, halogen atoms, phenyl groups and groups of the formula 6-NRaRb, 1 in which Raand Rbare the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms; 4 X1is a single bond, an oxygen atom, a sulfur atom or a group of the formula 6-N (R4)-, 1 in which R4is an alkyl group having 1 to 4 carbon atoms; 4 m is 0 or an integer from 1 to 8; 4 Y is a group of the formula 6 -(CH2)n-Y1-, 1 in which Y1is an oxygen atom or a sulfur atom; 4 n is an integer from 1 to 5; 4 Z is a group of the formula Vii 6 2 6. Derived thiazolidine under item 1, in which R1and R2are the same or different and each represents a hydrogen atom or alkyl group having 1-4 carbon atoms. 2 7. Derived thiazolidine under item 1, in which a and b are the same or different and each represents a hydrogen atom or a methyl, ethyl or through a group, or a and b together form a group of the formula or-CH2CH2-. 2 8. Derived thiazolidine under item 1, in which X is a group formly 6 W - (CH2)m- X1-, 1 in which W represents a phenyl group, coperta, alkoxygroup having 1 to 4 carbon atoms, halogen atoms, phenyl groups and groups of the formula 6-NRaRb, 1 in which Raand Rbare the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms; 4 X1is a single bond, an oxygen atom, a sulfur atom or a group of the formula 6-N (R4)-, 1 in which R4is methyl, ethyl or through the group; 4 m is 0 or an integer from 1 to 6. 2 9. Derived thiazolidine under item 1, in which Y is a group of the formula 6 -(CH2)n- Y1-, 1 in which Y1is an oxygen atom or a sulfur atom, 4 n is an integer from 1 to 5. 2 10. Derived thiazolidine under item 1, in which R1and R2are the same or different and each represents a hydrogen atom or alkyl group having 1 to 4 carbon atoms; 4 a and b are the same or different and each represents a hydrogen atom, a methyl, ethyl or through a group, or a and b together form a group of the formula 6 or-CH2CH2-; 4, X is a group of the formula 6 W -(CH2)m- X1-, 1 in which W is a phenyl group which is unsubstituted or substituted by 1 to 3 substituents, selected from alkyl groups having 1 to 4 NRaRb, 1 in which Raand Rbare the same or different and each represents a hydrogen atom or alkyl group having 1 to 8 carbon atoms; 4 X1is a single bond, an oxygen atom, a sulfur atom or a group of the formula 6-N (R4)-, 1 in which R4is methyl, ethyl or through the group; 4 m is 0 or an integer from 1 to 6; 4 Y is a group of the formula 6 -(CH2)n- Y1-, 1 in which Y1is an oxygen atom or a sulfur atom; 4 n is an integer from 1 to 5; 4 Z have the meanings given in paragraph 1. 2 11. Derived thiazolidine under item 1, in which R1and R2both hydrogen or one is hydrogen atom, and the other is an alkyl group having 1 to 4 carbon atoms. 2 12. Derived thiazolidine under item 1, in which a and b are the same or different and each represents a hydrogen atom, a methyl or ethyl group, or a and b together form a group of the formula 6 or CH2CH2-. 2 13. Derived thiazolidine under item 1, in which X is a group of the formula 6 W -(CH2)m- X1-, 4 in which W is a phenyl group which is unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of halogen atoms and methyl, ethyl, phenyl, amino, di 6-N(Me)-; 4 m is 0 or an integer from 1 to 6. 2 14. Derived thiazolidine under item 1, in which Y is a group of the formula 6 -(CH2)n- Y1-, 1 in which Y1is an oxygen atom or a sulfur atom; 4 n is an integer from 1 to 3. 2 15. Derived thiazolidine under item 1, in which R1and R2both represent a hydrogen atom or one of them represents a hydrogen atom, and the other is an alkyl group having 1 to 4 carbon atoms; 4 a and b are the same or different and each represents a hydrogen atom, a methyl or ethyl group, or a and b together form a group of the formula 6 or-CH2CH2-; 4, X is a group of the formula 6 W - (CH2)m- X1-, 1 in which W is a phenyl group which is unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of halogen atoms and methyl, ethyl, phenyl, amino, dimethylamino, methoxy, ethoxy groups; 4 X1is a single bond, an oxygen atom, a sulfur atom or a group of formula-N(Me)-; 4 m is 0 or an integer from 1 to 6; 4 Y is a group of the formula 6 -(CH2)n- Y1-, 1 in which Y1is an oxygen atom or a sulfur atom; 4 n is an integer from 1 to 3; 4 Z is a group of the formula Vii6 2 16. Derived thiazolidine under item 1, in which R1and R2both atom vodoprovidne of thiazolidine under item 1, in which the a - hydrogen atom and a hydrogen atom, a methyl or ethyl group, or a and b together form a group of the formula . 2 18. Derived thiazolidine under item 1, in which X is a group of the formula 6 W -(CH2)m- X1-, 1 in which W is halogen-substituted phenyl group, phenylfenesin, metoksifenilny or phenyl group; 4 X1is an oxygen atom or a sulfur atom; 4 m is 0 or an integer from 1 to 6. 2 19. Derived thiazolidine under item 1, in which Y is a group of the formula 6-CH2O - or -(CH2)2O-. 2 20. Derived thiazolidine under item 1, in which R1and R2both hydrogen or one is hydrogen atom, and the other is methyl, ethyl, sawn or ISO-propyl group; 4 a - hydrogen atom and a hydrogen atom or a methyl or ethyl group, or a and b together form a group of the formula ; 4, X is a group of the formula 6 W - (CH2)m- X1, 1 in which W is halogen-substituted phenyl group, phenylfenesin, metoksifenilny or phenyl group; 4 X1is an oxygen atom or a sulfur atom; 4 m is 0 or an integer from 1 to 6; 4 Y group of formula-CH2O - or -(CH2)2O-; 4 Z is a group of the formula Vii6 2 21. Derived thiazolidine under item 1, in which R1and R2both are a hydrogen atom or one and - the volume of hydrogen and a hydrogen atom or a methyl group, or a and b together form a group of the formula 2 23. Derived thiazolidine under item 1, in which X is a group of the formula 6 W - (CH2)m-O-, 1 in which W is phenyl, 3-chloraniline, 4-chloraniline, 3-metoksifenilny, 4-metoksifenilny or 4-phenylphenolate group; 4 m is 0 or an integer from 1 to 6. 2 24. Derived thiazolidine under item 1, in which Y is a group of formula-CH2O-. 2 25. Derived thiazolidine under item 1, in which R1and R2both hydrogen or one is hydrogen atom, and the other is a methyl or ethyl group; 4 R3is a hydrogen atom; 4 a - hydrogen atom and a hydrogen atom or a methyl group, or a and b together form a group of the formula 4, X is a group of the formula 6 W - (CH2)m-O- 1 in which W is phenyl, 3-chloraniline, 4-chloraniline, 3-metoksifenilny, 4-metoksifenilny or 4-phenylphenolate group; 4 m is 0 or an integer from 1 to 6; 4 Y is a group of the formula: -CH2O-; 4 Z is a group of the formula Vii 6 2 26. Derived thiazolidine under item 1, representing: 2 5-{4-[2-(3-phenyl-2-gidroksiprolina)propoxy] benzyl} -thiazolidine-2,4-dione; 2 5-{4-[2-(5-3'-chlorphenoxamine-2-oxoacridine-3-yl)ethoxy] -benzyl}thiazolidine-2,4-dione; 2 5-{4-[2-(5-3'-chlorphenoxamine is-yl)propoxy]benzyl} thiazolidine-2,4-dione; 2 5-{4-[2-(3-6'-phenylhexane-2-hydroxypropylamino)propoxy] -benzyl} thiazolidine-2,4-dione and2 5-{4-[2-(5-3'-chlorphenoxamine-2-oxoacridine-3-yl)butoxy]benzyl}thiazolidine-2,4-dione, 1, and their salts. 2 27. Pharmaceutical composition having hypoglycemic and gipolipidemicescoy activity and activity inhibition alsoreported, which includes an effective amount of the active compound in a mixture with a pharmaceutically acceptable carrier or diluent, wherein the active compounds it contains at least one derivative of thiazolidine according to any one of paragraphs. 1 - 26. 2 28. Method for the treatment or prevention of diseases of mammals, being treated with compounds with hypoglycemic or gipolipidemicescoy activity or activity inhibition alsoreported, introducing a specified mammal an effective amount of an active compound, characterized in that the active compounds are used at least one derivative of thiazolidine according to any one of paragraphs.1 - 26.

 

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,

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