Derivatives of thiazolidinedione or their pharmaceutically acceptable salts, pharmaceutical composition and method for the treatment or prevention of diseases

 

(57) Abstract:

The invention relates to a derivative of thiazolidinedione formula

,

where X is unsubstituted or substituted indayla, indolenine, asiandaily, asiandaily, imidazopyridine or imidazopyridine group; Y is an oxygen atom or a sulfur atom; Z-2,4-dioxothiazolidine-5-ylidenemethyl, 2,4-dioxothiazolidine-5-ylmethylene, 2,4-dioxoimidazolidin-5-ylmethylene, 3,5-dioxoimidazolidin-2-ylmethylene or N-gidroksilaminopurina group; R is a hydrogen atom, an alkyl group, alkoxygroup, halogen atom, hydroxy-group, a nitrogroup, kalkilya group or unsubstituted or substituted amino group; and m is an integer from 1 to 5. The compounds possess hypoglycemic and antidiabetic activities. On the basis of the proposed pharmaceutical composition and method for the treatment or prevention of disease. The method consists in the introduction to the mammal the compound of the above formula. 3 C. and 15 C.p. f-crystals, 7 PL.

The invention relates to a series of heterocyclic compounds with hypoglycemic and antidiabetic activities, to processes for their preparation and to their uses and compositions for this purpose.

Thus, the present invention is the creation of a number of new chemical compounds, which can be considered as derivatives of thiazolidine and oxazolidine or derivatives thereof open circuited ring.

Another, more specific object of the present invention is to provide such compounds, at least some of which may be suitable for treatment and/or prevention of various disorders, including one or more of the following: hyperlipemia, hyperglycemia, obesity, inadequate glucose tolerance, insulin resistance and diabetic complications.

Thus, in accordance with the present invention planilla, imidazopyridine or imidazopyrimidines group, unsubstituted or substituted by at least one Deputy, selected from the group consisting of the following substituents ;

Y is an oxygen atom or a sulfur atom;

Z is a group of the formula (i), (ii), (iii), (iV) or (V):

< / BR>
R is a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, halogen atom, hydroxy-group, a nitrogroup, kalkilya group in which an alkyl group having from 1 to 5 carbon atoms, a substituted aryl group having from 6 to 10 carbon atoms in the ring, or a group of the formula - NRaRbwhere Raand Rb(same or different) each is a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, kalkilya group in which an alkyl group having from 1 to 5 carbon atoms, a substituted aryl group having from 6 to 10 carbon atoms in the ring, aryl group having 6 to 10 carbon atoms in the ring, alifaticheskii carboxyaniline group having from 1 to 11 carbon atoms, aliphatic carboxyaniline group which has from 2 to 6 carbon atoms and which is substituted by an aryl group, having from 6 to 10 carbon atoms in the ring, or aromatizes the words from 1 to 5;

each of the substituents is an alkyl group having from 1 to 4 carbon atoms, aryl group having 6 to 10 carbon atoms, triptorelin group, allylthiourea having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, benzyloxy, halogen atom, hydroxy-group, acetoxygroup, phenylthiourea, nitrogroup, kalkilya group, or a group of the formula-NRaRbwhere Raand Rbsuch as mentioned above;

the above aryl groups and the aryl parts mentioned Uralkalij groups included in substituents are carbocyclic aromatic groups having from 6 to 10 carbon atoms in the ring, and unsubstituted or substituted by at least one Deputy, selected from the group consisting of substituents shown below;

each of the substituents is an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, halogen atom, hydroxy-group, the nitro-group, phenyl group, triptorelin group, or a group of the formula-NRaRbwhere Raand Rbsuch as mentioned above;

and their salts.

In accordance with the present invention it is also proposed, pharmaceutical is ffektivnoe the number of active (current) compounds in a mixture with a pharmaceutically acceptable carrier or diluent, and an active compound selected from the group consisting of compounds of the above formula (I) and their salts.

In accordance with this invention proposes a method of treatment or prevention of diabetes or hyperlipemia and their complications in a mammal, which may be people, (method) involving the introduction into the organism of a mammal an effective amount of an active compound, selected from the group consisting of the above compounds of formula (I) or their salts.

In accordance with the present invention provides methods of making compounds that (methods) are described in more detail below.

The compounds in accordance with the present invention, when X represents a group derived from indole cycle, it may be, for example, indol-1-ilen, indole-2-ilen, indole-3-ilen, indol-4-ilen, indol-5-ilen, indol-6-ilen, or indol-7-ilen group.

When X represents a group derived from indolinone cycle, it may be, for example, indolin-1-ilen, indolin-2-ilen, indolin-3-ilen, indolin-4-ilen, indolin-5-ilen, indolin-6-ilen or indolin-7-ilen group.

When X represents a group derived from isoindoline, 4-azaindole-6 - ilen, 4-isoindol-7-ilen, 5-isoindol-1-ilen, 5-azaindole-2-ilen, 5-azaindole-3-ilen, 6-isoindol-4-strong, 5-azaindole-6-ilen, 5 - isoindol-7-ilen, 6-isoindol-1-ilen, 6-azaindole-2-ilen, 6 - azaindole-3-ilen, 6-isoindol-4-ilen, 6-azaindole-5-ilen, 6 - isoindol-7-ilen, 7-azaindole-1-ilen, 7-azaindole-2-ilen, 7 - azaindole-3-ilen, 7-isoindol-4-ilen, 7-azaindole-5-ilen or 7 - azaindole-7-ilen group.

When X represents a group derived from isoindoline cycle, it may be, for example, 4-azaindole-1-ilen, 4-azaindole - 2-ilen, 4-azaindole-3-ilen, 4-azaindole-5-ilen, 4-azaindole - 6-ilen, 4-azaindole-7-ilen, 5-azaindole-1-ilen, 5-azaindole - 2-ilen, 5-azaindole-3-ilen, 5-azaindole-4-ilen, 5-azaindole - 6-ilen, 5-azaindole-7-ilen, 6-azaindole-1-ilen, 6-azaindole-2-ilen, 6-azaindole-3-ilen, 6-azaindole-4-ilen, 6 - azaindole-5-ilen, 6-azaindole-7-ilen, 7 azaindole-1-ilen, 7 azaindole-2-ilen, 7-asahidai-3-ilen, 7 azaindole-4-ilen, 7 - azaindole-5-ilen or 7-azaindole-6-ilen group.

When X represents a group derived from imidazopyridines cycle, it may be, for example, imidazo [4,5-b]pyridine-1-ilen, imidazo [4,5-b] pyridine-2-ilen imide is imidazo[4,5-c]pyridine-2-ilen, imidazo[4,5-c]pyridine-4-ilen, imidazo[4,5-c] pyridine-6-ilen, imidazo[4,5-c]pyridine-7-ilen, imidazo[5,4-b]pyridine-3-ilen, imidazo[5,4-b] pyridine-2-ilen, imidazo[5,4-b] pyridine-7-ilen, imidazo[5,4-b] pyridine-5-ilen, imidazo[5,4-b] pyridine-6-ilen, imidazo[5,4-c] pyridine-3-ilen, imidazo[5,4-c] pyridine-2-ilen, imidazo[5,4-c] pyridine-4-ilen, imidazo[5,4-c]pyridine-6-ilen, imidazo[5,4-c]pyridine-7-ilen, imidazo[1,2-a] pyridine-2-ilen, imidazo[1,2-a] pyridine-3-ilen, imidazo[1,2-a] pyridine-8-ilen, imidazo[1,2-a] pyridine-5-ilen, imidazo[1,2-a]pyridine-6-ilen or imidazo[1,2-a]pyridine-7-ilen group.

When X represents a group derived from imidazopyrimidines cycle, it may be, for example, imidazo[4,5-d]-pyrimidine-7-ilen, imidazo[4,5-d]pyrimidine-8-ilen or imidazo[4,5-d]pyrimidine-9-ilen group.

Any of the above groups which may be represented by the symbol X may be unsubstituted or substituted by at least one of the substituents listed above and shown in the example below. When the group is substituted, there is no particular limitation on the number of substituents, except as imposed by the number of substitutable positions or, often, spatial restrictions. But usually predgradie to the position of Deputy.

When R, Deputy or Deputy represents an alkyl group, this may be unbranched or branched alkyl group having from 1 to 4 carbon atoms, and examples include methyl, ethyl, sawn, ISO-propyl, bucilina, isobutylene, second-bucilina and tert-bucilina group, of which preferred is methyl group.

When R, Deputy or Deputy represents alkoxygroup, it can be unbranched or branched alkoxygroup having from 1 to 4 carbon atoms, and examples include methoxy, ethoxy-, propoxy-, isopropoxy, butoxy, isobutoxy-, second -, butoxy - and tert-butoxypropyl, of which preferred is a methoxy group.

When R, Deputy or Deputy represents a halogen atom, it may be, for example, an atom of bromine, chlorine, fluorine or iodine, of which the preferred atoms of bromine, chlorine and fluorine, and the most preferred chlorine atom.

When R is aracelio group, the alkyl part of this group has from 1 to 5 carbon atoms and may be unbranched or branched group, substituted aryl group, which itself may be the same as above and given Kilroy part of such groups include methyl, ethyl, sawn, ISO-propyl, boutelou, isobutylene, second-boutelou, tert-boutelou, pentelow, isopentanol, neopentylene and repentigny group (preferably methyl and ethyl groups). Examples of aryl groups are given below in connection with the substituents . Specific examples of such Uralkalij groups include benzyl, 2-phenylethylene (i.e. fenetylline), 1-phenylethylene, 3-phenylpropanol, 2 - phenylpropyl, 1-phenylpropyl, 4-phenylbutyl, 1 - phenylbutyl, 5-phenylpentane, 1-naphthylmethyl and 2 - naphthylmethyl groups, of which the preferred penicilina and benzyl groups, and most preferred benzyl group.

In accordance with another variant R, Deputy or Deputy may represent amino group or replaced by an amino group of formula-NRaRbwhere Raand Rbthat may be the same or different, selected from the following groups:

1) hydrogen atoms;

2) alkyl groups, having from 1 to 8 carbon atoms, which may be groups with unbranched or branched chain, for example, methyl, ethyl, sawn, ISO-propyl, bucilina, isobutylene, second-bucilina, tert-bucilina, pentilla, 2-pencilina, 3-p, exilda, 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, 1,1,3-trimethylpropyl, 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 groups, of which the preferred unbranched and branched alkyl groups, having from 1 to 4 carbon atoms, and most preferred methyl and ethyl groups;

3) kalkilya groups specified and shown in the example above in connection with the group, which can be represented by the radical R, and preferably such a group having from 7 to 11 carbon atoms;

4) aryl groups having from 6 to 10 carbon atoms, for example phenyl, 1-naftalina and 2-naftalina group;

5) aliphatic carboxyaniline group, which may be unbranched or branched groups having 1 to 11 carbon atoms, such as, for example, formyl, acetyl, propylaniline, Butyrina, isobutylene, bialoleka, pantaneira, hexanoyl, heptanoyl group, which have from 2 to 6 carbon atoms and a substituted aryl group and each of which preferably has a total of from 8 to 12 carbon atoms; examples of the aliphatic acyl group is the acyl group having from 2 to 6 carbon atoms, which are included in the list of aliphatic acyl groups represented by the radicals Raand Rbabove (preferably acetyl and propylaniline group), and examples of the aryl parts are those groups that are included in the above list aryl groups (preferably phenyl and naftalina group, particularly phenyl group), specific examples of the preferred aryl-substituted aliphatic acyl groups are phenylacetylene, 3-phenylpropionyl, 4-phenylbutyramide, 5-phenylmethanone, 6-phenylhexanoic, -methylphenylamine and dimethylphenylacetic groups, of which the preferred phenylacetylene group;

7) carbocyclic aromatic carboxyaniline groups in which the aryl group is the same as specified and shown in the example above aryl group (preferably phenyl and naftalina group, particularly phenyl group), and their examples are benzoline, 1-napolina and 2-naftagrup, which can be represented by the radical R, assistant or Deputy , are the following:

1) substituted amino groups, in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other is an alkyl group, such as methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino-, second -, butylamino-, tert-butylamino, pentylamine-, 2-pentylamine-, 3-pentylamine-, 2-methylbutylamine-, 3-methylbutylamine-, 1,1-dimethylpropylene-, 1,2-dimethylpropylene-, 2,2-dimethylpropylene, hexylamino-, 2-hexylamino-, 3-hexylamino-, 2-methylpentylamino, 3 methylpentylamino-, 4 methylpentylamino-, 1,1-dimethylbutylamino-, 1,2-dimethylbutylamino-, 1,3-dimethylbutylamino-, 2,2-dimethylbutylamino-, 2,3-dimethylbutylamino, 3,3-dimethylbutylamino-, 1,1,2-trimethylpropyl-, 1,2,2-trimethylpropyl, heptylamine, 2-heptylamine-, 3-heptylamine-, 4-heptylamine-, 3,3-dimethylpentylamine-, 2-ethylhexylamine and 1,1,3,3-tetramethylbutylamine-group;

2) substituted amino groups, in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aracelio group, such as benzylamino, 2-phenylethylamine, 1 phenylethylamine, 3 phenylpropylamine, 2-phenylpropylamine, 1 phenylpropylamine, 4-phenylbutane amino group, in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aryl group, such as phenylamino, 1 naphthylamine and 2-naphthylamine;

4) substituted amino groups, in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aliphatic acyl group, such as formamido-, acetamido-, propionamido, butyramide, isobutyramide, paulolino, pentanediamine, hexanamine, leptanillinae, octanoylthio, nonboiling, decanoylamino and undecanoate-group;

5) substituted amino groups, in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aryl-substituted aliphatic acyl group, such as phenylacetamido-, 3-phenylpropionamide-, 4-phenylbutyramide-, 5-phenylenediamine-, 6-phenylhexanoic-, -methylphenylacetic and-dimethylphenylacetate;

6) substituted amino groups, in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aromatic acyl group, such as benzamide, 1 naphthylamine - and 2-naphthylamines;

7) substituted amino groups, in which Raand Rbis an alkyl group, which may be the same or otlichayuschimisya amino group, in which one of the radicals Raand Rbrepresents an alkyl group, and the other Uralkaliy, such as N-ethyl-N-benzylamino, N-tert-butyl-N-benzylamino - and N-hexyl-N-benzylamino;

9) substituted amino groups, in which one of the radicals Raand Rbrepresents an alkyl group, and the other is aryl, such as N-methyl-N-phenylamino, N-ethyl-N-phenylamino - and N-octyl-N-phenylaminopropyl;

10) substituted amino groups, in which one of the radicals Raand Rbrepresents an alkyl group, and the other aliphatic acyl groups, such as N-propyl-N-acetylamino-, N-pentyl-N-propionamido - and N-ethyl-N-hexanamine-group;

11) substituted amino groups, in which one of the radicals Raand Rbrepresents an alkyl group, and the other aryl-substituted aliphatic carboxylic acyl group, such as N-ethyl-N-phenylacetylamino-, N-isopropyl-N-(2-phenylpropionyl)amino and N-methyl-N-(6-phenylhexanoic)amino;

12) substituted amino groups, in which one of the radicals Raand Rbrepresents an alkyl group, and the other aromatic acyl groups, such as N-methyl-N-benzoylamine, N-terbutyl-N-benzoylamine and N-heptyl-N-benzoylamino;

13) substituted amino groups, in the other, such as dibenzylamine, N-benzyl-N-(3-phenylpropyl)amino - N-benzyl-N-(2-naphthylmethyl)amino;

14) substituted amino groups, in which one of the radicals Raand Rbis aracelio group, and the other is aryl, such as N-benzyl-N-phenylamino - and N-(3-phenylpropyl)-N-phenylaminopropyl;

15) substituted amino groups, in which one of the radicals Raand Rbis aracelio group, and the other aliphatic acyl groups, such as N-benzyl-N-acetylamino-, N-benzyl-N-propionamido - and N-benzyl-N-pentanediamine;

16) substituted amino groups, in which one of the radicals Raand Rbis aracelio group, and the other aryl-substituted aliphatic carboxyaniline group, such as N-benzyl-N-phenylacetylamino - and N-benzyl-N-(4-phenylbutyl)amino;

17) substituted amino groups, in which one of the radicals Raand Rbis aracelio group, and the other aromatic acyl groups, such as N-benzyl-N-benzoylamine and N- (2-phenylethyl)-N-benzoylamino;

18) substituted amino groups, in which Raand Rb- aryl group, which may be the same or different from each other, such as diphenylamino-, N-(1-naphthyl)-N-phenylbrepresents an aryl group, and the other aliphatic carboxyaniline, such as N-phenyl-N-acetylamino-, N-phenyl-N-propionamido - and N-phenyl-N-exonerating;

20) substituted amino groups, in which one of the radicals Raand Rbrepresents an aryl group, and the other aryl-substituted aliphatic carboxyaniline group, such as N-phenyl-N-phenylacetylamino - and N-phenyl-N-(4-phenylbutyl)amino;

21) substituted amino groups, in which one of the radicals Raand Rbrepresents an aryl group, and the other aromatic carboxyaniline, such as N-phenyl-N - benzoylamine and N-phenyl-N-(2-naphtol)amino;

22) substituted amino groups, in which Raand Rb- aliphatic carboxyaniline group, which may be the same or different from each other, such as N,N-diatsetilamino-, N-acetyl-N-propionamido - and N-butyryl-N-exonerating;

23) substituted amino groups, in which one of the radicals Raand Rbrepresents aliphatic carboxyaniline group, and the other aryl-substituted aliphatic carboxyaniline group, such as N-acetyl-N-phenylacetylamino-, N-acetyl-N-(4-phenylbutyl)amino and N-butyryl-N-phenylacetylamino; amoxicilina group, and the other aromatic carboxyaniline group, such as N-acetyl-N-benzoylamine and N-butyryl-N-(2-naphtol)amino;

25) substituted amino groups, in which Raand Rb- arylsubstituted aliphatic carboxyaniline group, which may be the same or different from each other, such as N,N-diphenylacetylene-, N-phenylacetyl-N-(2-phenylpropionyl)amino and N-phenylacetyl-N-(4-phenylbutyl)amino;

26) substituted amino groups, in which one of the radicals Raand Rbrepresents aryl-substituted aliphatic carboxyaniline group, and the other aromatic carboxyaniline group, such as N-phenylacetyl-N - benzoylamine and N-phenylacetyl-N-(2-naphtol)amino group, and

27) substituted amino groups, in which Raand Rbaromatic carboxyaniline group, which may be the same or different, such as N, N-dibenzylamino - and N-benzoyl-N-(2-naphtol)amino group.

When the Deputy represents allylthiourea, it can be unbranched or branched allylthiourea having from 1 to 4 carbon atoms, examples of which include methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutyric, sec-butylthio and tert-butylthio may be unsubstituted or substituted by at least one Deputy, selected from the group consisting of substituents . Examples of unsubstituted aryl groups are, for example, phenyl, 1-naftalina and 2-naftalina group.

When the Deputy represents an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, halogen atom, hydroxy, nitro, phenyl or triptorelin group or the amino group of the formula-NRaRb, alkyl, alkoxy or amino group and a halogen atom can be the same as specified and shown in the example above in relation to substituents .

In the case of substituted aryl groups there are no special restrictions on the number capable of being deputies , except for the limitations imposed by the number of substitutable positions and possibly by spatial constraints. Usually preferred 1-5 substituents, and most preferred 1 or 2 substituent.

Examples of such substituted aryl groups include the following groups:

1) aryl groups substituted by at least one alkyl group having from 1 to 4 carbon atoms, such as 4-methylphenylene, 4-ethylvanillin, 4-propylaniline, 4-isopropylphenyl, 4-butylaniline, 4-isobutylphenyl, 4-second-butif the ilen, 5-butyl-1-naftalina, 4-isobutyl-1-naftalina, 4-sec-butyl-1-naftalina, 4-tert-butyl-1-naftalina, 4-methyl-2-naftalina, 5-ethyl-2-naftalina, 8-propyl-2-naftalina, 4-isopropyl-2-naftalina, 5-butyl-2-naftalina, 8-isobutyl-2-naftalina, 4-sec-butyl-2-naftalina, or 5-tertbutyl-2-naftalina group;

2) aryl groups substituted by at least one alkoxygroup having from 1 to 4 carbon atoms, such as 4-metoksifenilny, 4-ethoxyphenyl, 4-propoxyphenyl, 4-isopropoxyphenyl, 4-butoxyaniline, 4-solutocapillary, 4-second-butoxyaniline, 4-tert-butoxyphenyl, 4-methoxy-1-naftalina, 4-ethoxy-1-naftalina, 8-propoxy-1-naftalina, 4-isopropoxy-1-naftalina, 5-butoxy-1-naftalina, 4 isobutoxy-1-naftalina, 4-Deut-butoxy-1-naftalina, 4-tributoxy-1-naftalina, 4-methoxy-2-naftalina, 5-ethoxy-2-naftalina, 8-propoxy-2-naftalina, 4-isopropoxy-2-naftalina, 5-butoxy-2-naftalina, 8-isobutoxy-2-naftalina, 4-verboeket-2-naftalina or 5-tert-butoxy-2-naftalina group;

3) aryl groups substituted by a halogen atom, such as 4-bratinella, 4-chloraniline, 4-Fortunella, 4-idfamilia, 3-chloraniline, 3-Fortunella, 3-bratinella, 3-idfamilia, 4-bromo-1-naftalina, 4-chloro-1-naftaplin, 4-fluoro-2-naftalina, 4-bromo-2-naftalina, 4-chloro-2-naftalina, 4-iodine-2-naftalina, 5-bromo-2-naftalina, 5-chloro-2-naftalina, 5-fluoro-2-naftalina or 5-iodine-2-naftalina group;

4) aryl groups substituted by a hydroxy-group, such as 2-hydroxyproline, 3-hydroxyproline, 4-hydroxyproline, 4-hydroxy-1-naftalina, 5 - hydroxy-1-naftalina, 8-hydroxy-1-naftalina, 4-hydroxy-2-naftalina, 5-hydroxy-2-naftalina or 8-hydroxy-2-naftalina group;

5) aryl groups substituted by a nitro-group, such as 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, 4-nitro-1-naftalina, 5-nitro-1-naftalina, 3-nitro-1-naftalina, 4-nitro-2-naftalina, 5-nitro-2-naftalina or 8-nitro-2-naftalina group,

6) aryl group, substituted phenyl group, such as 3-phenylphenolate, 4-phenylphenolate, 4-phenyl-1-naftalina, 5-phenyl-1-naftalina, 8-phenyl-1-naftalina, 4-phenyl-2-naftalina, 5-phenyl-2-naftalina or 8-phenyl-2-naftalina group;

7) aryl groups, substituted triptorelin group, such as 3-triftormetilfullerenov, 4-triftormetilfullerenov, 4-trifluoromethyl-1-naftalina, 5-trifluoromethyl-1-naftalina, 8-trifluoromethyl-1-naftalina, 4-trifluoromethyl-2-naftalina, 5-trifluoromethyl-2-naftalina or 8-trifluoromethyl-2-attipoe, such as those substituted by an unsubstituted amino group, such as 2-aminoaniline, 3-aminoaniline, 4-aminoaniline, 4-amino-1-naftalina and 8-amino-2-naftalina group, and those substituted by a substituted amino group, for example:

I) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other is an alkyl group, such as 3-methyl-aminoaniline, 4-atramentaria, 3-propylaminoethyl, 3-isopropylacetanilide, 4-butylaminoethyl or 3-isobutyleneisoprene group;

(II) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aracelio group, such as 4-benzylaminopurine, 4-(2-phenylethylamine)phenyl, 4-(1-phenylethylamine)phenyl, 4-(4-phenylbutyramide)-phenyl or 4-(1 - naphthylethylene)phenyl group;

III) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aryl group, such as 4 - phenylenevinylene or 4-(1-naphthylamine)phenyl group;

IV) aryl groups substituted by a substituted amino group in which one of RA is immeditely, 4-acetamidophenyl, 4-butylaniline, 4-pivaloyloxymethyl, 4-exaniination, 4-octanoylthiophene or 4-underenumeration group;

V) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aryl-substituted aliphatic acyl group, such as 4-phenylacetonitrile, 4-(4-phenylbutyramide)phenyl, 4-(6-phenylhexanoic)-phenyl, 4 - (methylphenylethylamine)phenyl or 4-( , - dimethylphenylethylamine)phenyl group;

VI) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aromatic acyl group, such as 4-benzylaminopurine, 4-(1-naphthylamine)-phenyl or 4-(2-naphthylamine)phenyl group;

VII) aryl groups substituted by a substituted amino group in which Raand Rb, - alkyl groups, which may be the same or different from each other, such as 4-dimethylaminopyridine, 4-diethylaminophenyl or 4-(N-methyl-N-ethylamino)phenyl group;

VIII) aryl groups substituted by a substituted amino group in which one of radikalenerla, 4-(N-tert-butyl-N-benzylamino)phenyl or 4-(N-hexyl-N-benzylamino)-phenyl group;

IX) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an alkyl group, and the other is aryl, such as 4-(N-methyl-N-phenylamino)phenyl or 4-(N-octyl-N-phenylamino)phenyl group;

X) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an alkyl group, and the other aliphatic acyl group, such as 4-(N-propyl-N-acetylamino)phenyl or 4-(N-ethyl-N-hexanamine)phenyl group;

XI) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an alkyl group, and the other aryl-substituted aliphatic acyl group, such as 4-(N-ethyl-N-phenylacetylamino)phenyl or 4-[N-methyl-N-(6-phenylhexanoic)-amino]phenyl group;

XII) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an alkyl group, and the other aromatic acyl group, such as 4-(N-methyl-N-benzoylamine)phenyl or 4-(N-heptyl-N-benzoylamine)phenyl group;

XIII) aryl gruppi the same or different from each other, such as 4-dibenzylideneacetone or 4-[N-benzyl-N-(2-naphthylmethyl)amino]phenyl group;

XIV) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbis aracelio group, and the other is aryl, such as 4-(N-benzyl-N-phenylamino)phenyl or 4-[N-(3-phenylpropyl)-N-phenylamino]phenyl group;

XV) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbis aracelio group, and the other aliphatic acyl group, such as 4-(N-benzyl-N-acetamido)phenyl or 4-(N-benzyl-N-pentanediamine)phenyl group;

XVI) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbis aracelio group, and the other aryl-substituted aliphatic acyl group, such as 4-(N-benzyl-N-phenylacetylamino)phenyl or 4-[N-benzyl-N-(4-phenylbutyl)-amino]phenyl group;

XVII) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbis aracelio group, and the other aromatic acyl group, such as 4-(N-benzyl-N-benzoylamine)-phenyl or 4-[N-(2-phenylethyl)-N-benzoylamine]familyline group, which may be the same or different from each other, such as 4-diphenylmethylene or 4-[N-(2-naphthyl)-N-phenylamino]phenyl group;

XIX) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an aryl group, and the other aliphatic acyl group, such as 4-(N-phenyl-N-acetylamino)phenyl or 4-(N-phenyl-N-hexanamine)phenyl group;

XX) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an aryl group, and the other aryl-substituted aliphatic acyl group, such as 4-(N-phenyl-N-phenylacetylamino)-phenyl or 4-[N-phenyl-N -(4-phenylbutyl)amino]phenyl group;

XXI) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an aryl group, and the other aromatic acyl group, such as 4-(N-phenyl-N-benzoylamine)-phenyl group;

XXII) aryl groups substituted by a substituted amino group in which Raand Rb- aliphatic acyl groups which may be the same or different from each other, such as 4-dietilaminoetanola or 4-(N-butyryl-N-hexane dikalov Raand Rbrepresents an aliphatic acyl group and the other aryl-substituted aliphatic acyl group, such as 4-(N-acetylpenicillamine)phenyl or 4-(N-butyryl-N-phenylacetylamino)phenyl group;

XXIV) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an aliphatic acyl group and the other aromatic acyl group, such as 4-(N-acetyl-N-benzoylamine)phenyl or 4-[N-butyryl-N-(2-naphtol)-amino]phenyl group;

XXV) aryl groups substituted by a substituted amino group in which Raand Rb- aryl-substituted aliphatic acyl groups which may be the same or different from each other, such as 4-(N,N-diphenylacetylene)phenyl or 4-[N-phenylacetyl-N-(4-phenylbutyl)amino] phenyl group;

XXVI) aryl groups substituted by a substituted amino group in which one of the radicals Raand Rbrepresents aryl-substituted aliphatic acyl group and the other aromatic acyl group, such as 4-(N-phenylacetyl-N-benzoylamine)phenyl or 4-[N-phenylacetyl-N-(2-naphtol)amino]phenyl group;

XXVII) aryl groups substituted by a substituted amino group, the situations from each other, such as 4-dibenzoylethylene or 4-[N-benzoyl-N-(2-naphtol)amino]phenyl group.

When the Deputy is aracelio group, this group can be unsubstituted or substituted by one or more substituents listed and given as an example above. The group (excluding alternates, if any) preferably contains in total from 7 to 11 carbon atoms. Alkyl part aranceles group is an alkyl group having from 1 to 5 carbon atoms. Examples of such Uralkalij groups are benzyl, 2-phenylethylene, 1-phenylethylene, 3-phenylpropionate, 2-phenylpropionate, 1-phenylpropionate, 4-phenylbutyrate, 1-phenylmethylene, 5-phenylpentane, 1-naphthylmethyl and 2-naphthylmethyl group.

In the case of substituted Uralkalij groups there are no special restrictions on the number capable of being deputies , except for the limitations imposed by the number of substitutable positions and possibly by steric constraints. Usually preferred 1-5 substituents preferably 1-3 and most preferred 1 or 2 substituent.

Examples of such substituted Uralkalij groups are the following groups:

1) kalkilya group, substituted on the ilen, 4-propylaniline, 4-isopropylbenzyl, 4-butylaniline, 4-isobutylbenzene, 4-second-butylaniline, 4-tert-butylaniline, 4-methyl-1-naphthylmethyl, 5-ethyl-1-naphthylmethyl, 8-propyl-1-naphthylmethyl, 4-isopropyl-1-naphthylmethyl, 5-butyl-1-naphthylmethyl, 4-isobutyl-1-naphthylmethyl, 4-sec-butyl-1-naphthylmethyl, 4-tert-butyl-1-naphthylethylene, 4-methyl-2-naphthylmethyl, 5-ethyl-2-naphthylmethyl, 8-propyl-2-naphthylmethyl, 4-isopropyl-2-naphthylmethyl, 5-butyl-2-naphthylmethyl, 8-isobutyl-2-naphthylmethyl, 4-sec-butyl-2-naphthylmethyl or 5-tert-butyl-2-naphthylmethyl group;

2) kalkilya group, substituted by at least one alkoxygroup having from 1 to 4 carbon atoms, such as 4-methoxyaniline, 4-ethoxyaniline, 4-propoxybenzene, 4-isopropoxyaniline, 4-butoxyaniline, 4-isobutoxyethene, 4-second-butoxyaniline, 4-tert-butoxyaniline, 4-methoxy-1-naphthylmethyl, 5-ethoxy-1-naphthylmethyl, 8-propoxy-1-naphthylmethyl, 4-isopropoxy-1-naphthylmethyl, 5-butoxy-1-naphthylethylene, 4 isobutoxy-1-naphthylmethyl, 4-Deut-butoxy-1-naphthylmethyl, 4-tert-butoxy-1-naphthylmethyl, 4-methoxy-2-naphthylmethyl, 5-ethoxy-2-naphthylmethyl, 8-propoxy-2-attibutable-2-naphthylmethyl or 5-tert-butoxy-2-naphthylmethyl group;

3) kalkilya group substituted by a halogen atom, such as 4-brombenzene, 4-chloraniline, 4 - tormentilla, 4-odensala, 3-chloraniline, 3-tormentilla, 3-brombenzene, 3-odensala, 4-bromo-1-naphthylmethyl, 4-chloro-1-naphthylmethyl, 4-fluoro-1-naphthylmethyl, 4-iodine-1-naphthylmethyl, 5-chloro-1-naphthylmethyl, 5-fluoro-1-naphthylmethyl, 5-bromo-1-naphthylethylene, 8-chloro-1-naphthylmethyl, 4-fluoro-2-naphthylmethyl, 4-bromo-2-naphthylmethyl, 4-chloro-2-naphthylmethyl, 4-iodine-2-naphthylmethyl, 5-bromo-2-naphthylmethyl, 5-chloro-2-naphthylmethyl, 5-fluoro-2-naphthylmethyl or 5-iodine-2-naphthylmethyl group;

4) kalkilya group substituted by a hydroxy-group, such as 2 - hydroxybenzylidene, 3-hydroxybenzylidene, 4--hydroxybenzylidene, 4-hydroxy-1-naphthylmethyl, 5-hydroxy-1-naphthylmethyl, 8-hydroxy-1-naphthylmethyl, 4-hydroxy-2-naphthylmethyl, 5-hydroxy-2-naphthylmethyl or 8-hydroxy-2-naphthylmethyl group;

5) kalkilya group substituted by a nitro-group, such as 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, 4-nitro-1 - naphthylmethyl, 5-nitro-1-naphthylmethyl, 8-nitro-1-naphthylmethyl, 4-nitro-2-naphthylmethyl, 5-nitro-2-naphthylmethyl or 8-nitro-2-naphthylethylene grouppanel-1-naphthylethylene, 5-phenyl-1-naphthylmethyl, 8-phenyl-1-naphtylamine, 4-phenyl-2-naphthylmethyl, 5-phenyl-2-naphthylmethyl or 8-phenyl-2-naphthylmethyl group;

7) kalkilya group, substituted triptorelin group, such as 3-triphtalocyaninine, 4-triphtalocyaninine, 4-trifluoromethyl-1-naphthylmethyl, 5-trifluoromethyl-1-naphthylmethyl, 8-trifluoromethyl-1-naphthylmethyl, 4-trifluoromethyl-2-naphthylmethyl, 5-trifluoromethyl-2-naphthylmethyl or 8-trifluoromethyl-2-naphthylmethyl group;

8) kalkilya group, substituted by at least one unsubstituted or substituted amino group, such as those substituted by an unsubstituted amino group, such as 2-aminoaniline, 3-aminoaniline, 4-aminoaniline, 4-amino-1-naphthylethylene or 8-amino-2-naphthylmethyl group, and those substituted by a substituted amino group, for example:

I) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other is an alkyl group, such as 3-methylaminomethyl, 4-ethylaminomethyl, 3-propylaminoethyl, 3-isopropylaminomethyl, 4-butylaminoethyl or 3-izabelinamirabelina group;

II) kalkilya group, a substituted Zam is lilou group, such as 4-benzylaminopurine, 4-(2-phenylethylamine)-benzyl, 4-(1-phenylethylamine)benzyl, 4-(4-phenylbutyramide)benzyl or 4-(1-naphthylethylene)benzyl group;

III) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aryl group, such as 4-phenylenevinylene or 4-(1-naphthylamine)-benzyl group;

IV) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aliphatic acyl group, such as 4-formamidopyrimidine, 4-acetamidobenzoyl, 4-butylaniline, 4-pivaloyloxymethyl, 4-exaniination, 4-octaneenhancing or 4-andeconomically group;

V) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents a hydrogen atom, and the other aryl-substituted aliphatic acyl group, such as 4-phenylacetonitrile, 4-(4-phenylbutyramide)benzyl, 4-(6-phenylhexanoic)benzyl, 4 - (methylphenethylamino)benzyl or 4-( , -dimethylphenylacetic)benzyl group;

VI) and the place of the hydrogen atom, and the other aromatic acyl group, such as 4-benzylaminopurine, 4-(1-naphthylamine)benzyl or 4-(2-naphthylamine)benzyl group;

(VII) kalkilya group substituted by a substituted amino group in which Raand Rbis an alkyl group, which may be the same or different from each other, such as 4-dimethylaminobenzene, 4-diethylaminobenzylidene or 4-(N-methyl-N-ethylamino)benzyl group;

(VIII) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an alkyl group, and the other Uralkaliy, such as 4-(N-ethyl-N-benzylamino)benzyl, 4-(N-tert-butyl-N-benzylamino) benzyl or 4-(N-hexyl-N-benzylamino)-benzyl group;

(IX) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an alkyl group, and the other is aryl, such as 4-(N-methyl-N-phenylamino)benzyl or 4-(N-octyl-N-phenylamino)benzyl group;

(X) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an alkyl group, and the other aliphatic acyl group, such as 4-(N-propyl-N-acetylamino)-be what monography, in which the radicals Raand Rbrepresents an alkyl group, and the other aryl-substituted aliphatic acyl group, such as 4-(N-ethyl-N-phenylacetylamino) benzyl or 4-[N-methyl-N-(6-phenylhexanoic)amino]benzyl group;

XII) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an alkyl group, and the other aromatic acyl group, such as 4-(N-methyl-N-benzoylamine)-benzyl or 4-(N-heptyl-N-benzoylamine)benzyl group;

XIII) kalkilya group substituted by a substituted amino group in which Raand Rb- kalkilya group, which may be the same or different from each other, such as 4-dibenzylethylenediamine or 4-[N-benzyl-N-(2-naphthylmethyl)amino]benzyl group;

XXIV kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbis aracelio group, and the other is aryl, such as 4-(N-benzyl-N-phenylamino)benzyl or 4-[N-(3-phenylpropyl)-N-phenylamino]benzyl group;

XV) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbis aracelio group, and Domino)benzyl group;

XVI) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbis aracelio group, and the other aryl-substituted aliphatic acyl group, such as 4-(N-benzyl-N-phenylacetylamino)benzyl or 4-[N-benzyl-N-(4-phenylbutyl)amino]benzyl group;

XVII) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbis aracelio group, and the other aromatic acyl group, such as 4-(N-benzyl-N-benzoylamine)-benzyl or 4-[N-(2-phenylethyl)-N-benzoylamine]benzyl group;

XVIII) kalkilya group substituted by a substituted amino group in which Raand Rb- aryl group, which may be the same or different from each other, such as 4-diphenylbenzidine or 4-[N-(2-naphthyl)-N-phenylamino]benzyl group;

XIX) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an aryl group, and the other aliphatic acyl group, such as 4-(N-phenyl-N-acetylamino)benzyl or 4-(N-phenyl-N-hexanamine)benzyl group;

XX) kalkilya group, substituted substituted aminogroup aricescu acyl group, such as 4-(N-phenyl-N-phenylacetylamino)benzyl or 4-[N-phenyl-N-(4-phenylbutyl)amino]benzyl group;

XXI) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an aryl group, and the other aromatic acyl group, such as 4-(N-phenyl-N-benzoylamine)benzyl group;

XXII) kalkilya group substituted by a substituted amino group in which Raand Rb- aliphatic acyl groups which may be the same or different from each other, such as 4-diacetylpyridine or 4-(N-butyryl-N-hexanamine)benzyl group;

XXIII) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an aliphatic acyl group and the other aryl-substituted aliphatic acyl group, such as 4-(N-acetyl-N-phenylacetylamino)benzyl or 4-(N-butyryl-N-phenylacetylamino)benzyl group;

XXIV) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents an aliphatic acyl group and the other aromatic acyl group, such as 4-(N-acetyl-N-benzoylamine)benzyl or 4-[N-bucatarii and Raand Rb- aryl-substituted aliphatic acyl groups which may be the same or different from each other, such as 4-(N,N-diphenylacetylene)benzyl or 4-[N-phenylacetyl-N-(4-phenylbutyl)amino] benzyl group;

XXVI) kalkilya group substituted by a substituted amino group in which one of the radicals Raand Rbrepresents aryl-substituted aliphatic acyl group and the other aromatic acyl group, such as 4-(N-phenylacetyl-N-benzoylamine)benzyl or 4-[N-phenylacetyl-N-(2-naphtol)amino]benzyl group;

XXVII) kalkilya group substituted by a substituted amino group in which Raand Rbaromatic acyl groups which may be the same or different from each other, such as 4-dibenzoylbenzene or 4-[N-benzoyl-N-(2-naphtol)amino]benzyl group.

Specific examples of the substituted groups, is produced from indole, indolinone, azaindole, isoindolines, imidazopyridines and imidazopyrimidines cycles, each of which is substituted preferably 1-3 substituents , which may be represented by the symbol X are; for example:

group of indole cycle, such as Triveni the-ilen, 5-hydroxy-1-methylindol-3-ilen, 1-isopropylindole-3-ilen, 2-ethyl-1-methylindol-3-ilen, 5-methoxy-1-methylindol-3-ilen, 5-hydroxy-1,2-dimethylindole-3-ilen, 5-butoxy-1-methylindol-3-ilen, 1,4,7-trimethylol-3-ilen, 1,6-dimethylindole-3-ilen, 5-bromo-6-chloro-1-methylindol-3-ilen, 5-bromoindole-3-ilen, 5-hydroxy-1-isobutylene-3-ilen, 5-fluoro-1-methylindol-2-ilen, 5 - chloro-1-methylindol-2-ilen, 5-hydroxy-1-methylindol-2-ilen, 5 - methoxy-1-methylindol-2-ilen, 5-bromo-1-methylindol-2-ilen, 1-ethyl-5 - nitroindole-2-ilen, 1,5-dimethylindole-2-ilen, 5-amino-1 - methylindol-2-ilen, 5-acetamido-1-methylindol-2-ilen, 5-benzamido - 1-ethylindole-2-ilen, 1-methyl-5-methylaminomethyl-2-ilen, 5-butylamino-1-methylindol-2-ilen, 5-(N-benzoyl-N-methylamino)-1-methylindol-2-ilen, 1-methyl-5-phenylalaninol-2-ilen, 5-acetamidino-2-ilen, 5-benzamido-1-butional-2-ilen, 4-chloro-1-methylindol-2-ilen, 3-methoxy-1-methylindol-2-ilen, 6-fluoro-1-methylindol-2-ilen, 6-chloro-1-ethylindole-2-ilen, 6-methoxy-1-methylindol-2-ilen, 5,6-dimethoxy-1-methylindol-2-ilen, 7-methoxyindol-2-ilen, 1-methylindol-5-ilen, 1-butional-5-ilen, 1-ethylindole-5-ilen, 1-methylindol-4-ilen, 1-isopropylindole-4-ilen and 1-butional-4-ilen group;

group indolinone cycle, such as 5-the 2-ilen and 1-isopropylindole-2-ilen group;

group azaindole cycle, such as 1-methyl-7-azaindole-3-ilen, 1-isopropyl-7-azaindole-3-ilen, 1-methyl-7-azaindole-2-ilen and 1-methyl-6-azaindole-2-ilen group;

group isoindoline cycle, such as 1-methyl-7-azaindole-2-ilen, 1-ethyl-7-azaindole-2-ilen, 1-isopropyl-7-azaindole-2-ilen and 1-butyl-7-azaindole-2-ilen group;

group imidazopyridines cycle, such as 7-methylimidazo [4,5-b]pyridine-2-ilen, 1 butylimido[4,5-b] pyridine-2-ilen, 1 methylimidazo[4,5-b] pyridine-2-ilen, 1 propylimidazol[4,5-b] pyridine-2-ilen, 5-chloro-1-methylimidazo[4,5-b] pyridine-2-ilen, 5-methoxy-1-methylimidazo-[4,5-b]pyridine-2-ilen, 6,8-dibromomethane[1,2-a]pyridine-2-ilen, 8-hydroxyamide[1,2-a]pyridine-2-ilen, 6-chloroimidazo[1,2-a]pyridine-2-ilen, 2-methylimidazo[1,2-a] pyridine-7-ilen, 2-ethylimidazole[1,2-a] pyridine-8-ilen, 3 methylimidazo[5,4-b]pyridine-2-ilen, 3 ethylimidazole[5,4-b]pyridine-2-ilen, 3,7-dimethylimidazo[5,4-b] pyridine-2-ilen, 5-chloro-3-methylimidazo[5,4-b] pyridine-2-ilen, 5-chloro-3-phenylimidazo[5,4-b] pyridine-2-ilen, 5-bromo-3-methylimidazo[5,4-b] pyridine-2-ilen, 3-methyl-6-triptoreline[5,4-b]pyridine-2-ilen, 3-isopropyl-6-triptoreline[5,4-b] pyridine-2-ilen, 3-(3-Chlorobenzyl)-imidazo[5,4-b] pyridine-2-ilen, 3 benzimidazo[5,4-b] -peridiniidae[5,4-b] pyridine-2-ilen, 6-bromo-3-ethylimidazole[5,4-b] pyridine-2-ilen, 6-bromo-3-phenylimidazo[5,4-b] pyridine-2-ilen, 6-chloro-3-methylimidazo[5,4-b]-pyridine-2-ilen, 3-butyl-6-chloroimidazo[5,4-b] pyridine-2-ilen, 5-methoxy-3-methylimidazo[5,4-b]pyridine-2-ilen, 3-ethyl-5-methoxyimino[5,4-b]pyridine-2-ilen, 5-methoxy-3-propylimidazol[5,4-b] pyridine-2-ilen, 5-methoxy-3-phenylimidazo[5,4-b] pyridine-2-ilen, 3-benzyl-5-methoxyimino[5,4-b] pyridine-2-ilen, 3-(3-chlorophenyl)-5-methoxyimino-[5,4-b]pyridine-2-ilen, 5-hydroxy-3-methylimidazo[5,4-b] -pyridine-2-ilen, 3-ethyl-5-hydroxyamide[5,4-b]pyridine-2-ilen, 3-benzyl-5-hydroxyamide[5,4-b]pyridine-2-ilen, 3 phenylimidazo[5,4-b] pyridine-2-ilen, 3-(4-chloro-phenyl)-imidazo[5,4-b]]pyridine-2-ilen, 3-(3-chlorophenyl)imidazo-[5,4-b] pyridine-2-ilen, 3-(2-were)imidazo [5,4-b] pyridine-2-ilen, 5-chloro-3-(3-chlorophenyl)imidazo[5,4-b] pyridine-2-ilen, 5-methoxy-3-(3-methoxyphenyl)imidazo[5,4-b]pyridine-2-ilen, 5-hydroxy-3,6-dimethylimidazo[5,4-b]pyridine-2-ilen, 5-methoxy-3,6-dimethylimidazo [5,4-b] -pyridine-2-ilen, 3 methylimidazo[5,4-b]pyridine-5-ilen, 2,3-dimethylimidazo[5,4-b]pyridine-5-ilen, 3-ethyl-2-methylimidazo[5,4-b] pyridine-5-ilen, 3-methyl-2-phenylimidazo-[5,4-b] pyridine-5-ilen, 2-[2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl] -3-methylimidazo[5,4-b] pyridine - 5-ilen, 2-(3-chlorophenyl)-3-metromela, 3-methyl-5-phenylimidazo[5,4-b]pyridine-2-ilen, 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-methylimidazo[5,4-b] pyridine - 2-ilen, 5-ethoxy-3-methylimidazo[5,4-b] pyridine-2-ilen, 5-isopropoxy-3-methylimidazo[5,4-b]pyridine-2-ilen, 5-acetoxy-3-methylimidazo[5,4-b]pyridine-2-ilen, 3-ethyl-5-phenoxy-6-triptoreline[5,4-b] pyridine-2-ilen, 7-chloro-3-methylimidazo-[5,4-b] pyridine-2-ilen, 7-chloro-3-propylimidazol[5,4-b]pyridine-2-ilen, 6-hydroxy-3,5,7-trimethylimidazo[5,4-b]pyridine-2-ilen, 3,5,7-trimethyl-6-nitroimidazo[5,4-b] pyridine-2-ilen, 6-amino-3,5,7-trimethylimidazo[5,4-b] pyridine-2-ilen, 3-methyl-5-methylamino-imidazo[5,4-b]pyridine-2-ilen, 5-dimethylamino-3-methylimidazo[5,4-b] pyridine-2-ilen, 5-(N-butyl-N-ethylamino)-3-methylimidazo[5,4-b] pyridine-2-ilen, 3-methyl-5-phenylimidazo[5,4-b] pyridine-2-ilen, 5-benzylamino-3-methyl-imidazo[5,4-b]pyridine-2-ilen, 5-(N-ethyl-N-phenylamino)-3-methylimidazo[5,4-b]pyridine-2-ilen, 5-acetamido-3-methylimidazo[5,4-b] pyridine-2-ilen, 5-benzoylamine 3 methylimidazo[5,4-b] pyridine-2-ilen, 3-methyl-6-nitroimidazo-[5,4-b] pyridine-2-ilen, 6-amino-3-methylimidazo[5,4-b]-pyridine-2-ilen, 6-benzoylamino-3-methylimidazo[5,4-b] -pyridine-2-ilen, 6-valeryl-3-butylimido[5,4-b] pyridine-2-ilen, 5-benzyloxy-3-methylimidazo[5,4-b]pyridine-2-ilen, 2-hydroxy-3-methylimidazo[tilty-3H-imidazo[5,4-b]pyridine-5-ilen, 3-methyl-2-methylthioribose[5,4-b]pyridine-5-ilen, 3-benzyl-2-butyldibenzo[5,4-b]-pyridine-5-ilen, 5-tert-butylamino-3-methylimidazo[5,4-b] -pyridine-2-ilen, 5-tert-butylamino-3-propylimidazol[5,4-b] pyridine-2-ilen, 3,5,7-trimethylimidazo[5,4-b] pyridine-2-ilen, 3-(3-chlorophenyl)-5,7-dimethylimidazo[5,4-b] pyridine-2-ilen, 3-(3,5-di-tert-butyl-4-hydroxybenzyl)-5,7-dimethylimidazo[5,4-b] pyridine - 2-ilen, 5-acetoxy-3-methylimidazo[5,4-b]pyridine-2-ilen, 5-acetoxy-3-ethylimidazole-[5,4-b] pyridine-2-ilen, 6-methoxy-3-methylimidazo[5,4-c] -pyridin-2-ilen, 1 methylimidazo[4,5-C]pyridine-2-ilen and 1 butylimido[4,5-c] pyridine-2-ilen group;

group imidazopyrimidines cycle, such as 3-methylimidazo [5,4-d] pyrimidine-2-ilen, 3 ethylimidazole-[5,4-d] pyrimidine-2-ilen and 3-(3-methylbenzyl)imidazo-[5,4-d] pyrimidine-2-ilen group.

Of the compounds in accordance with the present invention preferred are those compounds of formula (I) and their salts, in which:

(A1) X - indayla, indolenine, asiandaily, imidazopyridine or imidazopyrimidines group, unsubstituted or substituted by substituents listed below;

the Deputy is an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, b is up to 4 carbon atoms, triptorelin group, the nitro-group, the amino group of the formula - NRaRbwhere Raand Rbthe same or different and each is a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, kalkilya group having from 7 to 11 carbon atoms, aryl group having 6 to 10 carbon atoms, aliphatic acyl group having from 1 to 11 carbon atoms, aryl-substituted aliphatic acyl group having from 8 to 12 carbon atoms, or an aromatic acyl group having from 7 to 11 carbon atoms, aryl group having 6 to 10 carbon atoms, which is unsubstituted or substituted by at least one Deputy, selected from the group consisting of substituents , and referred to the Deputy represents an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, a halogen atom, a hydroxy-group, a nitro-group, phenyl group, triptorelin group or the amino group of the formula-NRaRbwhere Raand Rbsuch as those mentioned above, provided that if Raor Rbrepresents an aryl group or a group containing an aryl group itself aryl group is not substituted for another group of formula-NR
and/or (A2) Y is an oxygen atom or a sulfur atom;

and/or (A3) Z - 2,4-dioxothiazolidine-5-ylidenemethyl, 2,4-dioxothiazolidine-5-ylmethylene, 2,4-dioxoimidazolidin-5-ylmethylene, 3,5-dioxoimidazolidin-2-ylmethylene or N-gidroksilaminopurina group;

and/or (A4) R is a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, or a halogen atom;

and/or (A5) m = an integer from 1 to 5;

and especially compounds in which X is the same as specified in (A1), Y is the same as specified in (A2), Z is the same as specified in (A3), R is the same as specified in (A4), and m is the same as specified in (A5).

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

(B1) X - indayla, indolenine, imidazopyridine or imidazopyrimidines group, unsubstituted or substituted by 1-3 substituents mentioned below;

the Deputy is an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, benzyloxy, halogen atom, hydroxy-group, acetoxygroup, phenylthiourea, allylthiourea having from 1 to 4 atoms ug is b the same or different and each is a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, kalkilya group having from 7 to 11 carbon atoms, aryl group having 6 to 10 carbon atoms, aliphatic acyl group having from 1 to 11 carbon atoms, aryl-substituted aliphatic acyl group having from 8 to 12 carbon atoms, or an aromatic acyl group having from 7 to 11 carbon atoms,

aryl group having from 6 to 10 carbon atoms, which is not substituted or substituted by at least one Deputy, selected from the group consisting of the Deputy , and the Deputy represents an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, a halogen atom, a hydroxy-group, a nitro-group, phenyl group, triptorelin group or the amino group of the formula-NRaRbwhere Raand Rbsuch as mentioned above,

or kalkilya group having from 7 to 11 carbon atoms, which is not substituted or substituted by at least one Deputy, selected from the group consisting of substituents ;

and/or (B2) Y is an oxygen atom;

and/or (B3) Z - 2,4-dioxothiazolidine-5-ylidenemethyl, 2,4-dioxothiazolidine, the within from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, or a halogen atom;

and/or (B5) m = an integer from 1 to 5;

and especially compounds in which X is the same as specified in (B1), Y is the same as specified in (B2), Z is the same as specified in (B3), R is the same as specified in (B4), and m is the same as specified in (B5).

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

(C1) X - indayla, indolinyl or imidazopyridine group, unsubstituted or substituted by 1-3 substituents mentioned below;

the Deputy is an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, benzyloxy, halogen atom, hydroxy-group, acetoxygroup, phenylthiourea, allylthiourea having from 1 to 4 carbon atoms, triptorelin group, the nitro-group, the amino group of the formula-NRaRb,

where Raand Rbthe same or different and each is a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, kalkilya group having from 7 to 11 carbon atoms, aryl group having 6 to 10 carbon atoms, aliphatic acyl group having from 1 to 11 atoms Zilina group, having from 7 to 11 carbon atoms,

aryl group having from 6 to 10 carbon atoms, which is not substituted or substituted by at least one Deputy, selected from the group consisting of the Deputy , and the Deputy represents an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, a halogen atom, a hydroxy-group, a nitro-group, phenyl group, triptorelin group or the amino group of the formula-NRaRbwhere Raand Rbsuch as mentioned above,

or kalkilya group having from 7 to 11 carbon atoms, which is not substituted or is substituted by 1-3 substituents selected from the group consisting of substituents ;

and/or (C2) Y is an oxygen atom;

and/or (C3) Z - 2,4-dioxothiazolidine-5-ylidenemethyl or 2,4-dioxothiazolidine-5-ylmethylene group;

and/or (C4) R is a hydrogen atom, a methoxy group, ethoxypropan, a fluorine atom or a chlorine atom;

and/or (C5) m = an integer from 1 to 5;

and especially compounds in which X is the same as specified in (S1), Y is the same as specified in (S2), Z is the same as specified in (C3), R is the same as specified in (C4), and m is the same as specified in (C5).

Even more preferred compounds in accordance with the present izobreteniya, unsubstituted or substituted by 1-3 substituents mentioned below;

the Deputy is an alkyl group having from 1 to 4 carbon atoms, alkoxygroup having from 1 to 4 carbon atoms, benzyloxy, halogen atom, phenylthiourea, allylthiourea having from 1 to 4 carbon atoms, triptorelin group or phenyl group;

and/or D2) Y is an oxygen atom;

and/or (D3) Z - 2,4-dioxothiazolidine-5-ylmethylene group;

and/or (D4) R is a hydrogen atom or a methoxy group;

and/or (D5) m = an integer from 1 to 5;

and especially compounds in which X is the same as specified in (D1), Y is the same as specified in (D2), Z is the same as specified in (D3), R is the same as specified in (D4), and m is the same as specified in (D5).

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

(E1) X - imidazopyridine group, unsubstituted or substituted by 1-3 substituents mentioned below;

Deputy - methyl group having from 1 to 4 carbon atoms, ethyl group, ISO-propyl group, a methoxy group, ethoxypropan, propoxylate, isopropoxide, benzyloxy, a fluorine atom, a chlorine atom, phenylthiourea, methylthiourea, ethylthiourea or phenyl gr is R - a hydrogen atom;

and/or (E5) m = an integer from 1 to 5;

and especially compounds in which X is the same as specified in (E1), Y is the same as specified in (E2), Z is the same as specified in (E3), R is the same as specified in (E4), and m is the same as specified in (E5).

Each connection in accordance with the present invention contains in the molecule a core group and can therefore be converted by acids into salts by traditional methods. There is no particular restriction on the nature of such salts, provided that if the connection must have a medical application, they must be pharmaceutically acceptable, i.e. not less active or is less active and not more or unacceptable toxic more toxic than the original compound. However, when the connection is not intended for medical use, and is used as an intermediate product in the production of other compounds, it is not even this restriction on the nature of the salts that can be formed. Examples of such salts are salts of mineral acids, in particular halogen (such as hydrofluoric, Hydrobromic, itestosterone or hydrochloric acid), nitric, perchloric, coal, sulfuric or FOS who consultationa; salt arylsulfonyl, such as benzosulfimide or paratoluenesulfonyl; salts of organic carboxylic acids, such as acetic, fumaric, tartaric, oxalic, maleic, malic, succinic, benzoic, almond, ascorbic, lactic, gluconic, or citric acid; and salts of amino acids such as glutamic or aspartic acid. Preferred pharmaceutically acceptable salts.

In addition, the compounds in accordance with the present invention can be converted into a salt by means of traditional methods. Examples of such salts are salts of alkaline metal such as sodium, potassium or lithium; salts of alkaline earth metal such as barium or calcium; salts of other metals, such as magnesium or aluminum. Preferred pharmaceutically acceptable salts.

Due to the presence of asymmetric carbon atoms the compounds of formula (I) in accordance with the present invention may exist in the form of various isomers. So, when replacing indolinone or isoindoline cycle in position 2 or 3 carbon atoms in these positions are asymmetric, and when Z represents a 2,4-dioxothiazolidine-5-ylmethylene or 2,4-dioxoimidazolidin-NII only one molecular formula (I), but the present invention covers both the individual isomers and mixtures thereof including racemates), and the isomers may be present in such mixtures in any proportions. When using technology stereospecific synthesis or as raw materials use of optically active compounds, the individual isomers may be obtained directly, and if you get a mixture of isomers, the individual isomers may be obtained by conventional methods of separation.

The compounds of formula (I) where Z represents a 2,4-dioxothiazolidine-5-ylmethylene, 2,4-dioxothiazolidine-5-ylidenemethyl, 2,4-dioxoimidazolidin-5-ylmethylene or 3.5-dioxoimidazolidin-2-ylmethylene group can exist in various tautomeric isomers as shown in the following diagrams, and shown at the end of the description.

All tautomers obtained on the basis of the above formula (I), and a mixture of equal or unequal masses of these tautomers represented by a single formula. Therefore, the present invention covers all of these isomers and mixtures of these isomers.

In addition, the present invention also covers all the solvate (e.g., hydrates) of compounds of formula (I) and their salts, when is also all connections which can be transformed into the body of a living mammal, such as man, in the compound of formula (I) or its salt by the action of metabolism, i.e., the so-called "drug precursors (prodrugs) of compounds of formula (I) and their salts.

Examples of some compounds in accordance with the present invention are given in the following formulas (1-1) to(1-5) listed at the end of the description.

In the above formulae the substituents such as those described in one of the following table.1-5, respectively. That is, PL.1 relates to formula (I-1), table 2 - the formula (I-2), and so on up the table.5, which relates to formula (I-5). In the tables use the following abbreviations:

Ac - acetyl

Bu - butyl

iBu is isobutyl

tBu is tert-butyl

Bz - benzyl

Et - ethyl

Me - methyl

Ph Patil

Pr - propyl

iPr is isopropyl

Prn - propionyl

Of the above compounds, particularly preferred compounds NN 1-1, 1-2, 1-3, 1-6, 1-57, 1-58, 1-62, 1-72, 1-81, 1-91, 1-93, 1-106, 1-121, 1-122, 1-125, 1-130, 1-134, 1-135, 1-137, 1-140, 1-142, 1-153, 1-156, 1-158, 1-161, 1-177, 1-179, 1-180, 1-182, 1-183, 1-207, 1-218 and 2-100, from which the compounds NN 1-1, 1-57; 1-62, 1-91, 1-93, 1-106, 1-122, 1-125, 1-130, 1-134, 1-137, 1-140, 1-142, 1-153, 1-156, 1-177, 1-179, 1-180, 1-182, 1-183, 1-207, 1-218 and 2-100 more preferable. Even more predpochtite the flaxes connection NN: 1-93 5-{ 4-(3-methylimidazo [5,4-b]pyridine-2-ylethoxy)-benzyl}thiazolidine-2,4-dione;

1-125. 5-{ 4-(5-chloro-3-methylimidazo[5,4-b]pyridine-2 - ylethoxy)-benzyl} thiazolidine-2,4-dione;

1-142. 5-{ 4-(5-methoxy-3-methylimidazo[5,4-b]pyridine-2-ylethoxy) -benzyl}thiazolidine-2,4-dione;

1-153. 5-{ 4-(5-hydroxy-3-methylimidazo [b, 4-b] pyridine-2-ylethoxy)benzyl}thiazolidine-2,4-dione;

182.5-{4-(5-ethoxy-3-methylimidazo[5,4-b]pyridine-2 - ylethoxy)-benzyl}thiazolidine-2,4-dione;

1-183. 5-{ 4-(5-isopropoxy-3-methylimidazo[5,4-b] pyridine-2 - ylethoxy)benzyl}thiazolidine-2,4-dione.

Compounds in accordance with the present invention can be obtained by various methods well known in the field of production of compounds of this General type. For example, they can be obtained in accordance with the following schemes A, B, C, D and E reactions:

Scheme of A reaction. This is a General scheme that can be used to obtain the compounds in accordance with the present invention, when Z represents a group of the formula (i), (ii), (IV) or (iv) listed at the end of the description.

In the above formulas (scheme A)

X and m are such as listed above;

R' is an alkyl group having 1 to 5 carbon atoms, which may be unbranched or branched group, for example any of those groups having 1 to 5 carbon atoms, which are included in the city of Jerusalem.):

< / BR>
where

Tr - triphenylethylene group.

Stage A1. On stage A1 obtain the connection formula (III) by restoring the compounds of formula (II).

The reaction can be carried out using a reducing agent. The character used in this reaction, the reducing agent is not critical, and any substance commonly used in reactions of this type may be equally applied here. Examples of such reducing agents include metal hydrides, such as borohydride lithium, borohydride sodium, lambrogini sodium, sociallyengaged or diisopropylaminoethyl.

The reaction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane or heptane; ethers, such as diethyl ether, tetrahydrofuran or dioxane; amides, such as dimethylformamide, dimethylacetamide rezannykh solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature in the range from cooling with ice before heating, for example to a temperature reverse drain (education phlegmy) reaction medium, and preferably with cooling with ice or at about room temperature. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time from 0.5 h to several days.

The reaction is preferably carried out in an alcohol or in a mixture of one or more alcohols and other organic solvents in the presence of lithium borohydride at a temperature between room temperature and the temperature of the return flow of the reaction medium during the period of time from 1 h to 1 day or in a hydrocarbon, or a simple ester in the presence of sociallyengaged or diisobutylaluminium when cooling or nagrywanie formula (III) and the compound of formula (IV) (in the formula Y, R and Z' such as the above) reactions Mitsunobu [(O. Mitsunobu, Synthesis, 1 (1981)].

The reaction is usually carried out in a solvent in the presence of at least one azo compounds and at least one phosphine.

There is no particular restriction on the nature of the azo compounds, and any compounds that are commonly used in reactions of this type can be equally applied here. Examples of such azo compounds are diethylazodicarboxylate and 1,1'-(azodicarbon)dipiperidino. Similarly, there is also no particular restriction on the nature of the phosphines, and their examples include triphenylphosphine and tributylphosphine.

The reaction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane or heptane; halogenated hydrocarbons, such as chloroform, methylene chloride or 1,2-dichloroethane; ethers, such as those to whom methyltestosterone; and mixtures of any two or more of these solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature ranging from room temperature to heating, for example to the temperature of the return flow of the reaction medium, and more preferably at a temperature ranging from room temperature to 60oC. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time from several hours to several days, and more preferably from 5 h to 3 days.

Stage A3. On stage A3 receive the compound of formula (I). This can be any of the compounds in accordance with the present invention, except those in which Z represents a group of formula (V).

The reaction is carried out by introducing the compounds of formula (V) into interaction with the acid, such as triperoxonane, triptorelin is S="ptx2">

When using the solvent, there is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons such as benzene, toluene, xylene, hexane or heptane; halogenated hydrocarbons, such as chloroform, methylene chloride or carbon tetrachloride; ethers, such as diethyl ether, tetrahydrofuran or dioxane; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide; esters such as ethyl acetate or methyl acetate; water; and mixtures of any two or more solvents.

The reaction can be conducted in a wide range of temperatures and the precise temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature in the range from cooling with ice to room temperature. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of reagents used and dissolve the straps from several tens minutes to several tens of hours, and preferably 0.5 to 10 hours

This stage can also be carried out by catalytic hydrogenation of compounds of formula (V). There is no particular restriction on the nature of the catalyst, and any hydrogenation catalyst commonly used in reactions of this type may be equally applied here. Examples of such hydrogenation catalysts are palladium on charcoal, palladium black, platinum oxide and platinum black, of which the preferred palladium on coal.

The reaction is normally and preferably carried out in the presence of a solvent, there is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane or heptane; halogenated hydrocarbons, such as chloroform, methylene chloride or carbon tetrachloride; ethers, such as diethyl ether, tetrahydrofuran or dioxane; alcohols, such as methanol, ethanol or isopropanol; amides, such as dimethylformamide, dimethylacetal is raveena in a wide range of temperatures, and the exact temperature is not important to this invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature ranging from room temperature to heating, for example at a temperature reverse flow of the reaction mixture, preferably at room temperature or with heating. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, a sufficient period of time from several hours to several days, and more preferably from 1 h to 1 day.

Scheme B reactions (listed at the end of the description). This method can be used to obtain compounds of formula (I) in which Y represents an oxygen atom and Z represents a group of the formula (i) or (ii), i.e., 2,4-dioxothiazolidine-5-ylidenemethyl or 2,4-dioxothiazolidine-5-ylmethylene group, i.e. compounds of formula (VII) and (VIII) respectively.

Stage B1. At stage B1 get compound of formula (VI) by treating the compounds of formula (III) base (first step) and then the interaction of the resulting phermeldahyde (the second step).

There is no special limitation on the character used as the first stage of the base, and equally there can be used any base commonly used in this type of reaction. An example of such a base is sodium hydride.

The reaction of the first stage is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane or heptane; ethers, such as diethyl ether, tetrahydrofuran or dioxane; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphoramide; and mixtures of any two or more of these solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature in the range from cooling with ice before heating, for example to a temperature is depending on many factors, especially the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time, from several tens of minutes to one day.

After the reaction of the first step can be carried out the second stage by adding to the reaction mixture of a derivative of formula (VIa) para-forventelige, then give the mixture a chance to react.

The reaction of the second step can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature ranging from room temperature to heating, for example to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time from several tens minutes to several days.

Stage B2 At the point.

The reaction can be carried out in the presence or absence of a catalyst. When the reaction is carried out in the presence of a catalyst, there is no particular restriction on the nature of the catalyst, and equally there can be used any catalyst commonly used in this type of reaction. Examples of such catalysts are sodium acetate, the acetate piperidine and benzoate piperidine.

The reaction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane or heptane; ethers, such as diethyl ether, tetrahydrofuran or dioxane; alcohols, such as methanol, ethanol or isopropanol; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide; halogenated hydrocarbons such as methylene chloride, chloroform or 1,2-dichloroethane; NITRILES, such as acetonitrile or propionitrile; complex is

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction under heating, for example, to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time from 1 to 50 hours.

Stage B3. On stage B3 obtain the connection formula (VIII) by restoring the compounds of formula (VII) by catalytic hydrogenation. There is no particular restriction on the nature of the catalysts, and equally there can be used any hydrogenation catalysts commonly used in reactions of this type. Examples of such hydrogenation catalysts are palladium on coal and palladium mobile, preferably palladium on coal.

The reaction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature espeeially and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane or heptane; ethers, such as diethyl ether, dioxane or tetrahydrofuran; alcohols, such as methanol, ethanol or ISO-propanol; organic acids such as formic, acetic or propionic acid; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphoramide; and mixtures of any two or more of these solvents.

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

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature ranging from room temperature to heating, for example to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is carried out at specified is, and more preferably from 1 hour to 1 day.

This stage can also be carried out by treating the compounds of formula (VII) with a metal hydride according to the procedure described in WO 93/A.

The scheme of reactions (listed at the end of the description). This method, which can be used to obtain compounds of formula (I) in which Y represents an oxygen atom and Z represents a group of formula (IV) or (V) i.e., 3,5-dioxoimidazolidin-2-ylmethylene or N-hydroxyacetylamino group, i.e. compounds of formula (X) and (XI) respectively.

In the above formula scheme C X, R and m such as those listed above.

Stage C1. At the stage S1 receives the connection of the formula (IX) by the interaction of the compounds of formula (VI) which can be obtained as described in scheme In the reaction with hydroxylamine (preferably the hydrochloride) as the first stage with the subsequent (second stage) the repair of the product.

The reaction of the compound of formula (VI) with hydroxylamine (hydrochloride) is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction of the Examples of suitable solvents are hydrocarbons (which may be aliphatic or aromatic), such as benzene, toluene, xylene, hexane or heptane, ethers such as diethyl ether, dioxane or tetrahydrofuran; alcohols, such as methanol, ethanol or isopropanol, amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide; halogenated hydrocarbons such as methylene chloride, chloroform or 1,2-dichloroethane; NITRILES, such as acetonitrile or propionitrile; esters such as ethyl formate or ethyl acetate; amines such as pyridine, triethylamine or N,N-aminobutiramida-N-ethylamine; and mixtures of any two or more of these solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as it was installed, it carries out the reaction at a temperature ranging from room temperature to heating, for example to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many conditions, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time is this stage can be carried out by hydrogenation in the presence of a reducing agent. There is no particular restriction on the nature of the used reducing agent, and equally there can be used any reducing agent commonly used in this type of reaction. Examples of such reducing agents are metal hydrides, such as sociallyengaged, diisobutylaluminium, borohydride lithium, borohydride sodium or lambrogini sodium.

The reaction of the second step is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane or heptane; ethers, such as diethyl ether, dioxane or tetrahydrofuran; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide, alcohols, such as methanol, ethanol or isopropanol; and mixtures of two or more of these solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical gledelig from cooling with ice to heat, for example, to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time, from several tens of minutes to one day, and more preferably from 1 to 10 hours

Stage C2. On stage C2 receive the connection formula (X) by the interaction of the compounds of formula (IX) with trimethylsilylcyanation.

The reaction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, such as benzene, toluene, xylene, hexane or heptane; ethers, such as diethyl ether, dioxane or tetrahydrofuran; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide; halogenated hydrocarbons, such as m eacce can be carried out in a wide temperature range, and the exact temperature is not important for the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature in the range from cooling with ice before heating, for example to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, especially the reaction temperature or the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time from several tens minutes to several days.

The compound obtained of the formula (X) is a compound in accordance with the present invention.

Stage C3. On stage C3 receive the compound of formula (XI) by the interaction of the compounds of formula (IX) with N-(chlorocarbonyl) isocyanate.

The reaction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvent is lol hexane or heptane, ethers such as diethyl ether, tetrahydrofuran or dioxane; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide, halogenated hydrocarbons such as methylene chloride, chloroform or 1,2-dichloroethane, NITRILES, such as acetonitrile or propionitrile; esters such as ethyl formate or ethyl acetate; and mixtures of any two or more of these solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature in the range from cooling with ice before heating, for example to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time from several tens minutes to several tens of hours.

Scheme D reactions (listed at the end of the description). This method, which can be used is lidin-5-ylmethylene or 2,4-dioxoimidazolidin-5-ylmethylene group, i.e., compounds of formula (XV).

In the above formula scheme D:

X - same as above, but preferably is imidazopyridine or imidazopyrimidines group;

Y, R and m are such as listed above;

Y' is an oxygen atom or a sulfur atom;

Q - lower alkoxycarbonyl group, formyl group, a protected formyl group, carboxyl group or hydroxy-group; and

HaIo - halogen atom.

Stage D1. On stage D1 receive compound of formula (XIV) the interaction of the compounds of formula (XII) with the compound of the formula (XIII) in the presence of a base.

There is no particular restriction on the nature of the used grounds, and equally there can be used any base commonly used in this type of reaction. Examples of such bases are inorganic bases, such as hydrides (such as sodium hydride or potassium hydride) and a carbonate (such as potassium carbonate or sodium carbonate; and organic bases such as triethylamine.

The reaction is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it does not have the time to some extent. Examples of suitable solvents are hydrocarbons (which may be aliphatic or aromatic, such as benzene, toluene, xylene, hexane or heptane; ethers, such as diethyl ether, tetrahydrofuran or dioxane, amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphoramide, and mixtures of any two or more of these solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at a temperature in the range from cooling with ice before heating, for example to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time from 0.5 h to several days.

The reaction is most preferably carried out with cooling or heating or at room temperature Amidah or a mixture of at least one amide with MCT 1 to 10 hours

The compounds of formula (XIV), which is obtained in this way are new compounds and serve as important intermediates for producing compounds of formula (I) in accordance with the present invention. Therefore, these compounds of formula (XIV) are also part of the present invention.

Stage D2. Stage D2 get the connection formula (XV) one of the following two methods (a) and (b).

Stage 2(a), the Compound of formula (XV) can be obtained by the coupling of compounds of formula (XIV) in which Q is the lowest alkoxygroup, with a derivative of 2,3-diaminopyridine or derived 5,4-diaminopirimidina.

When Q is lower alkoxycarbonyl group, it preferably has a total of 2 to 7 carbon atoms (i.e., CNS part has 1 to 6 carbon atoms) and may be unbranched or branched. Examples of such groups are methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, solutionline, second-butoxycarbonyl, tert-butoxycarbonyl, ventilatsiooniga, isobutylacetophenone, neopentylglycol, 2-motivationally, 1-ethylpropylamine, 4 is Bonilla, 3,3-dimethylethoxysilane, 2,2-dimethylethoxysilane, 1,1-dimethylethoxysilane, 1,2-dimethylethoxysilane, 1,3-dimethylethoxysilane, 2,3-dimethylethoxysilane, 2-tivocommunity, hexyloxybenzoyl and isohexadecane group. Of them preferred alkoxycarbonyl groups which have 1 to 4 carbon atoms, preferably methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl and solutionline group, and most preferably methoxycarbonyl and ethoxycarbonyl group.

The reaction is normally and preferably carried out in the presence or in the absence of solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons, preferably aromatic, such as benzene, toluene or xylene, ethers such as diethyl ether, tetrahydrofuran or dioxane, amides, such as dimethylformamide, dimethylene or propionic acid; and mixtures of any two or more of these solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction under heating, for example, to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, if the reaction is performed in the above-mentioned preferred conditions, it is usually sufficient period of time from 3 hours to several days.

The reaction is most preferably carried out in the absence of solvent with heating at a temperature of from 50oC to 150oC during the period of time from 5 hours to 2 days.

Stage D2(b). In accordance with another alternative, the compound of formula (XV) can be obtained by the coupling of compounds of formula (XIV), where Q represents a formyl group, at the first stage derived from 2,3-diaminopyridine or a derivative of 4,5-diaminopirimidina and then, at the second stage of processing of the product by the oxidizing agent.

The reaction usually is althemore solvent provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are hydrocarbons (which may be aliphatic or aromatic, such as benzene, toluene, xylene, hexane or heptane; ethers, such as diethyl ether, tetrahydrofuran, dioxane or 1,2-dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide or hexamethylphosphorotriamide; alcohols, such as methanol, ethanol or isopropanol; acids such as acetic or propionic; sulfoxidov, such as dimethyl sulfoxide; and mixtures of any two or more of these solvents.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to conduct the reaction at about room temperature or with heating, for example, to the temperature of the return flow of the reaction mixture. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. One is from 1 h to several days.

Then (second stage) the product is treated with an oxidant. There is no particular restriction on the nature of the oxidant, and equally there can be used any oxidizing agent commonly used in reactions of this type. Examples of such oxidizing agents are iodine, silver oxide and leads to compounds, which lead, of which preferred is iodine.

Processing oxidant is normally and preferably carried out in the presence of a solvent. There is no particular restriction on the nature of the solvent, provided that it has no adverse effect on the reaction or on the involved reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents are the solvents mentioned above for the first stage, preferably ethers.

The reaction can be conducted in a wide range of temperatures, and the precise reaction temperature is not critical to the present invention. Usually, as has been established, it is advisable to carry out the reaction with heating. Required for the reaction time can also be changed in wide ranges depending on many factors, particularly the reaction temperature and the nature Ipoh, it is usually sufficient period of time from 1 h to several days.

In the compound of formula (XIV), where Q represents a protected formyl group, formylamino group can be removed before the connection will be subjected to the reactions of the stage D2. Examples of such protected formyl groups are, for example, dimethoxymethane, diethoxymethane, 1,3-dioxane-2-ilen, 1,3-dioxolane-2-ilen, 1,3-dition-2-ilen and 1,3-ditiolan-2-ilen group. Formylamino group can be removed by conventional methods well known in the art, for example by introducing the compounds of formula (XIV) in contact with a traditional agent to remove the protection under the conditions conventionally used to remove the protection. These conditions are described in T. W. Green: Protective Groups in Organic Synthesis (John Wiley and Sons Ed) or J. F. W McOmie: Protective Groups in Organic Chemistry (Plenum Press Ed.).

Scheme E reactions (listed at the end of the description). This method, which can be used to obtain compounds of formula (I) where Z represents a group of formula (ii) or (iii), i.e., 2,4-dioxothiazolidine-5-ylmethylene or 2,4-dioxoimidazolidin-5-ylmethylene group, i.e. compounds of formula (XV).

In the above formula scheme E, Q, Y, Y', R' and m are such as listed above.

formula (XVI) in the presence of a base. This reaction is essentially the same as that described for stage D1 schema D, and can be carried out using the same reagents and reaction conditions.

Stage E2. At stage E2 obtain the connection formula (XVIII) by restoring the compounds of formula (XVII).

The reaction can be carried out by conventional catalytic hydrogenation or by using any reducing agent capable of restoring the nitrogroup, such as zinc-acetic acid or tin-hydrochloric acid.

Stage E3. At the stage of the receive E3 compound of formula (XIX), subjecting the compound of formula (XVIII) the reaction of arilirovaniya on Neervana.

Used for the reaction conditions are well known and essentially similar to those described in the application N Sho 55-22657 Kokai patent Japan or S. Oae et al.: Bull. Chem. Soc., Japan, 53, 1065 (1980).

Stage E4. At stage E4 obtain compound of formula (XIV) the interaction of the compounds of formula (XIX) with urea or thiourea followed by hydrolysis of the resulting product.

Compounds used for this reaction are well known and essentially similar to those disclosed in the aforementioned application N Sho 55-22657 patent Japan.

In the above-described stages of the product of each stage may, if desired, be isolated from the reaction mixture by traditional methods at the end of each reaction and, if necessary, the resulting compound can then be purified by conventional methods, e.g. by column chromatography, recrystallization, the resultant deposition rates or run like a well-known procedures. An example of one such method includes adding a solvent to the reaction mixture, extraction of the target compounds and, finally, the Stripping of the solvent from the extract. The obtained residue may be purified by column chromatography through silica gel or a similar adsorbent to obtain the target compound in the form of a pure sample.

Biological activity. The compounds of formula (I) and their salts have the ability to reduce the level of sugar in the blood, get rid of obesity, to fix a impaired glucose tolerance, suppress hepatic recovery of glucose, reduce the level of lipids in blood and suppress alsoreported. Therefore, they are suitable on the ineptia, nephropathy, neuropathy, cataract, angina and arteriosclerosis), and also associated with obesity, hypertension and osteoporosis.

Compounds in accordance with the present invention can be introduced into the body in different forms depending, as is well known in this area, subject to cure the violation and the age, condition and body weight of the patient. For example, by oral administration of compounds they can be prepared in the form of tablets, capsules, granules, powders or syrups, and for parenteral administration they may be prepared in the form of solutions for injection (intravenous, intramuscular or subcutaneous administration), drugs for drip infusion or suppositories. For use through the mucous membranes of the eye, they can be prepared in the form of eye drops or eye ointments. These dosage forms can be prepared by conventional methods and, if necessary, the active ingredient can be mixed with any conventional additives, such as filler, binder, loosening, lubricating, corrective and solubilizers substance, excipient to form a suspension, emulsifier or covering substance. Although d is ogliastro treatment or prevention, the method of administration and the form of the medicinal product, the recommended daily dose for an adult patient person is from 0.01 to 2000 mg of the compound, and it can be administered in one single dose or divided doses.

Activity of compounds in accordance with this invention is illustrated by the following experiments.

Experiment 1. Hypoglycemic activity. Used animals for testing were male mice of the SC, each of which had a body mass of at least 40, the compound was mixed with a mixture (1: 1 by volume) of polyethylene glycol 400 and water. In the body of each animal was administered orally with the test compound in the amount shown in the table.6, and then allowed him to freely eat for 18 hours At the end of this time took the blood from the tail vein without anesthesia. To determine the level of blood glucose (BGL) by analyzer glucose (GL-101 production F. Mitsubishi Casey Co." or Glucoroder-F manufacturing f. "Shino The Test.").

The hypoglycemic effect was calculated by the following equation:

Hypoglycemic effect (%) = [(BGLs- BGLt)/BGLs100,

where

BGLs- the level of glucose in the blood in grove in the group, which was introduced test the connection.

The results are shown in table.6, in which each connection in accordance with the present invention designated by the number of one of the following examples, in which is illustrated the receipt thereof.

As can be seen from the table.6, the compounds in accordance with the present invention showed excellent activity.

Experiment 2.

Inhibition alsoreported. Aldozoreduktaza lens cow's eye was isolated and partially purified by the method of S. Hyman and J. H. Kinoshita [J. Biol. Chem. , 240, 877 (1965)] and K. Inagaki, I. Miwa and J. Okuda [Arch. Biochem. Biophys. , 316, 337 (1982)], and its activity was determined photometrically according to the method of Varma et alk., [Biochem. Pharmac., 25, 2505 (1976)]. Inhibition of enzyme activity was measured for compounds in accordance with the present invention at a concentration of 5 μg/ml, and the measured values used to calculate values IC50. The results are shown in the following table.7.

Experiment 3.

The toxicity. The toxicity of compounds in accordance with the present invention was tested on rats male G divided into 5 groups. The test compound is administered orally in the body of each test animal at a dose of 50 mg/kg Jivotnymi observed over the next 2 weeks and during this period there were no abnormalities that could be attributed to the test compounds. When a significant dose introduced into the body of each animal, zero mortality shows that the compounds in accordance with the present invention have very low toxicity.

Thus, the compounds in accordance with the present invention have excellent activity in combination with a very low toxicity, which makes them ideally suited for therapeutic applications.

Further, the present invention is illustrated by the following non-limiting examples. In these examples, where there are connections numbers, these numbers correspond to those identified in the preceding table.1-5. Getting some of the original materials used in some of these examples are illustrated subsequent receipts.

Example 1. 5-[4-(Indolin-2-ylethoxy)benzyl] thiazolidin-2,4 - dione (Compound N 1-59).

A mixture of 3.55 g of 5-[4-(1-tert-butoxycarbonylamino-2 - ylethoxy)benzyl]-3-triphenyltetrazolium-2,4-dione (obtained as described in obtaining 4) and 30 ml triperoxonane acid was stirred at room temperature in tecnocarpent sodium, then it was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The obtained residue was purified by column chromatography through silica gel, using as eluent a mixture (2:1 by volume) hexane and ethyl acetate, and the result was 0,41 g specified in the connection header. This product was dissolved in ethanol and precipitated by adding water, which gave a powder, melting at 55,8 to 58.2oC.

Example 2. 5-[4-(1-Methylindolin-2-ylethoxy)benzyl] thiazolidin-2,4-dione (Compound 1-62 N)

To a solution of 2.50 g of 5-[4-(1-methylindolin-2-ylethoxy)benzyl] -3-triphenyltetrazolium-2,4-dione (obtained as described in obtaining 7) in 25 ml of methylene chloride was added 3.1 ml triperoxonane acid, and the resulting mixture was stirred at room temperature for 1 h In the end of this time the reaction mixture was treated by following the procedure described in example 1, and the result was 1.20 g specified in the title compound, melting at 46,1-48,9oC.

Example 3. 5-{ 4-[2-(Indolin-1-yl)ethoxy] benzyl} thiazolidine-2,4-dione (Compound N 1-57)

Povtoryalis)ethoxy]benzyl} -3-triphenyltetrazolium-2,4-dione (obtained, as described in 10) and 3 ml triperoxonane acid, and the result was 170 mg specified in the title compound, melting at 132,8 - 135,6oC.

Example 4. 5-{ 4-[2-(Indol-3-yl)ethoxy] benzyl} thiazolidine-2,4-dione (Compound No. 1-2). ) Repeated a similar procedure to that described in example 2, except that used to 1.77 g of 5-{4-[2-(indol-3-yl)ethoxy] benzyl}-3-triphenyltetrazolium-2,4-dione (obtained as described in 11), 53 ml of methylene chloride and 0.3 ml triperoxonane acid, and as a result got to 0.67 g specified in the title compound, melting at 42,6-44,5oC.

Example 5. 5-{ 4-[2-(3-Triphenylmethyl-1-yl, ethoxy] benzyl}-thiazolidine-2,4-dione (Compound N 1-3). Repeating a similar procedure to that described in example 2, except that the used of 2.33 g of 5-{4-[2-(indol-1-yl)ethoxy]benzyl}- 3-triphenyltetrazolium-2,4-dione (obtained as described in obtaining 14), 25 ml of methylene chloride and 3.1 ml triperoxonane acid, and the result was 2.20 g specified in the title compound, melting at 66,6-70oC.

Example 6. 5-{ 4-[2-(Indol-1-yl)ethoxy] benzyl} thiazolidine-2,4-dione (Compound N 1-1). A solution of 2.05 g of 5-{4-[2-(indol-1-yl, ethoxy]benzyl}-3-triphenyl is hydrogen and in the presence of 3.1 g of 10% (m/m) of palladium on coal, first at room temperature for 30 min, and then at 60oC for 2 h and at 80oC for 3 h In the end of this period the reaction mixture was filtered to remove catalyst and the filtrate was concentrated by evaporation under reduced pressure. Then the concentrate was purified by column chromatography through silica gel, using as eluent a mixture (2:1 by volume) hexane and ethyl acetate, and received in the result of 1.06 g specified in the title compound, melting at 42,3-44,6oC.

Example 7. 5-{4-(3-Methylimidazo[5,4-b]pyridine - 2-ylethoxy)benzyl}-thiazolidine-2,4-dione (Compound 1-93 N).

Repeating a similar procedure to that described in example 6, except that used 500 mg of 5-{4-(3-methylimidazo [5,4-b]pyridine-2-ylethoxy)benzyl} -3-triphenyl-methylthiazolidine-2,4-dione (obtained as described in obtaining 16), 1 g of 10% (m/m) of palladium on coal and 100 ml of methanol, and the result was 77 mg specified in the title compound, melting at 223-225oC.

Example 8. 5-{ 4-[2-(7-Isoindol-1-yl)ethoxy]benzyl} thiazolidine-2,4-dione (Compound 1-72 N).

Repeating a similar procedure to that described in example 2, except that used 2.50 g 5-{4-[2-(7-isoindol-1-yl)ethoxy]benzyl} -3-triveneto acid, and the result was 0.84 g specified in the title compound, melting at 200,0-202,4oC.

Example 9. 5-{4-(Imidazo[1,2-a]pyridine-2-ylethoxy)benzyl} thiazolidine-2,4-dione (Compound 1-106 N)

Repeating a similar procedure to that described in example 1, except that the injected 3.0 g of 5-{4-(imidazo-[1,2-a] pyridine-2-ylethoxy)benzyl}-3-triphenyltetrazolium-2,4-dione (obtained as described in obtaining 21) in cooperation with 30 ml triperoxonane acid and reaction was performed for 1 h At the end of this period the reaction mixture was freed from triperoxonane acid by distillation under reduced pressure. To the residue was added aqueous potassium carbonate solution and ethyl acetate, and the resulting precipitated insoluble material was collected by filtration, dried over anhydrous sodium sulfate and recrystallized from ethanol, resulting in 0.8 g specified in the title compound, melting at 197-202oC.

Example 10. 5-[4-(1-Methylindol-2-ylethoxy)benzyl] thiazolidin-2,4-dione (Compound 1-6 N)

Repeating a similar procedure to that described in example 6, except that used 3,24 g of 5-[4-(1-methylindol-2 - ylethoxy)benzyl] -3-triphenyltetrazolium-LTTE got 1,49 g specified in the connection header, melting at 174,3-175,5oC.

Example 11. 5-[4-{ 2-(Imidazo[1,2-a]pyridine-2-yl)ethoxy}benzyl] -thiazolidine-2,4-dione (Compound 1-107 N).

Repeating a similar procedure to that described in example 2, except that used to 0.94 g of 5-[4-{2-(imidazo[1,2-a]pyridine - 2-yl)ethoxy} benzyl]-3-triphenyltetrazolium-2,4-dione (obtained as described in obtaining 27), 4 ml of methylene chloride and 1 ml triperoxonane acid, and the result was indicated in the title compound as crude product. This product was purified by column chromatography through silica gel, using as eluent a mixture (2:1 by volume) hexane and ethyl acetate and then a mixture (1:2 by volume) of ethyl acetate and tetrahydrofuran, and the result was 287 mg specified in the title compound, melting at 205,9-207,0oC (decomposition).

Example 12. 5-{4-(3-Ethylimidazole[5.4-b]pyridine-2-ylethoxy)benzyl}- thiazolidine-2,4-dione (Compound 1-121 N).

To 300 mg of 5-{4-(3-ethylimidazole[5,4-b]pyridine-2-ylethoxy)benzyl}-3 - triphenyltetrazolium-2,4-dione (obtained as described in obtaining 29) was added 12 ml of a mixture (3:1 by volume) of acetic acid and water, and the resulting mixture was stirred at 60oC for 2 hours In to it was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using as eluent ethyl acetate and obtained 85 mg specified in the title compound, melting at 210-212oC.

Example 13. 5-{4-(1-Methylimidazo[4.5-b]pyridine-2 - ylethoxy)benzyl}-thiazolidine-2,4-dione (Compound 1-122 N).

Repeating a similar procedure to that described in example 12, except that used 4.1 g of 5-{4-(1-methylimidazo[4,5 - b]pyridine-2-ylethoxy)benzyl} -3-triphenyltetrazolium-2,4-dione (obtained as described in obtaining 31) and 160 ml of a mixture (3:1 by volume) of acetic acid and water, and the result was indicated in the title compound as crude product. This crude product was vykristallizovyvalas rubbing with ethyl acetate, gave 1.45 g specified in the title compound, melting at 231-232oC.

Example 14. 5-[4-{3-(3-Methylimidazo[5,4-b]pyridine-2-yl)propoxy}benzyl] -thiazolidine-2,4-dione (Compound 1-123 N).

Repeating a similar procedure to that described in example least 12, thiazolidin-2,4-dione (obtained, as described in obtaining 35) and 10 ml of a mixture (3:1 by volume) of acetic acid and water, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using the method of gradient elution with mixtures of hexane and ethyl acetate in ratios from 1:3 to 0:1 by volume as the eluent, and the result was 93 mg specified in the title compound, melting at 185-186oC.

Example 15. 5-{ 4-(1H-Imidazo[4.5-b]pyridine-2-ylethoxy)benzyl}- thiazolidine-2,4-dione (Compound 1-91 N)

To 200 mg of 2,3 - diaminopyridine was added 1.13 g of 4-(ethoxycarbonylmethoxy)benzylcyanide-2,4-dione (obtained as described in obtaining 31), and the resulting mixture was stirred at 110oC for 2 days. At the end of this time the reaction mixture was treated with 3 N. aqueous hydrochloric acid and then selecively by adding an aqueous solution of ammonia. The aqueous mixture was evaporated to dryness under reduced pressure and then the residue was purified by column chromatography through silica gel, using a gradient elution method, with mixtures of ethyl acetate and ethanol in ratios from 1:0 to 10:1 by volume) as eluent. Prod is placed, melting at 247-248oC.

Example 16. 5-{4-(3,7-Dimethylimidazo[5,4-b]pyridine-2 - ylethoxy)benzyl} thiazolidine-2,4-dione (Compound 1-124 N).

Repeating a similar procedure to that described in example 12, except that used 1.7 g of 5-{4-(3,7-dimethylimidazo [5,4-b] pyridine-2-ylethoxy)benzyl}-3-triphenyltetrazolium-2,4 - dione (obtained as described in obtaining 41) and 16 ml of a mixture (3:1 by volume) of acetic acid and water, and got the result mentioned in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using the method of gradient elution with mixtures of hexane and ethyl acetate in ratios from 1:1 to 1:2 by volume as the eluent. The product was vykristallizovyvalas by trituration with ethyl acetate, resulting in 0.28 g specified in the title compound, melting at 205-207oC.

Example 17. 5-{ 4-(5-Chloro-3-methylimidazo[5,4-b] pyridine-2 - ylethoxy)-benzyl}thiazolidine-2,4-dione (Compound N 1-125). Repeating a similar procedure to that described in example 12, except that he used to 1.16 g of 5-{4-(5-chloro-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl}-3 - triphenyltetrazolium-2,4-dione is Lucile specified in the title compound as crude product. This product has vykristallizovyvalas by trituration with ethyl acetate, resulting in 0,38 g specified in the title compound, melting at 222-223oC.

Example 18. 5-{ 4-(3-Methyl-6-triptoreline[5,4 - b]pyridine-2-ylethoxy)benzyl}thiazolidine-2,4-dione (Compound No. 1 - 130).

To a solution of 3.00 g of 3-amino-2-methylamino-5-triptoreline in a mixture of 6 ml of ethanol and 6 ml of acetic acid was added to 4.16 g of 5-[4-(2-oksidoksi)benzyl] thiazolidin-2,4-dione (obtained as described in obtaining 47), and the resulting mixture was stirred at room temperature for 4 h In the end of this time the reaction mixture was freed from solvent by distillation under reduced pressure. To the residue was added 50 ml of 1,2-dimethoxyethane and 5.2 g of iodine, and the resulting mixture was stirred at 60oC for one day. At the end of this time the reaction mixture was poured into water, then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using as eluent a mixture (1:1 by volume) hexane and ethyl acetate. PR is inane, melting at 212 - 214oC.

Example 19. 5-{4-(3-Methylimidazo[5,4 - b]pyridine-2-ylethoxy)benzyl}-thiazolidine-2,4-dione (Compound N 1-158).

Repeating a similar procedure to that described in example 12, except that used 0.24 g of 5-{4-(3-methylimidazo [5,4-b]pyridine-2-ylethoxy)benzyl} -3-triphenyltetrazolium-2,4 - dione (obtained so described in obtaining 51) and 8 ml of a mixture (3:1 by volume) of acetic acid and water, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using the method of gradient elution with mixtures of ethyl acetate and ethanol in ratios from 1:0 to 10:1 by volume as the eluent, and as a result received 30 mg specified in the title compound, melting at 244-246oC.

Example 20. 5-(4-{3-(4-Chlorbenzyl)imidazo[5,4 - b]pyridine-2-ylethoxy}-benzyl)thiazolidine-2,4-dione (Compound N 1-134).

Repeating a similar procedure to that described in example 18, except that used 1.20 g of 3-amino-2-(4 - chlorbenzyl)aminopyridine (obtained as described in the obtaining of 53) of 1.36 g of 5-[4-(2-oksidoksi)benzyl]thiazolidin-2,4-dione (obtained so that the received specified in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using the method of gradient elution with mixtures of hexane and ethyl acetate in ratios from 1:1 to 1:2 by volume as the eluent, and the result was 0.40 g specified in the title compound, melting at 211-213oC.

Example 21. 5-(4-{3-(4-phenylbenzyl)imidazo[5,4-b] pyridine-2-ylethoxy}benzyl)thiazolidine-2,4-dione (Compound 1-135 N).

Repeating a similar procedure to that described in example 12, except that used 0.9 g 5-(4-{3-(4-phenylbenzyl)imidazo[5,4-b] pyridine-2-ylethoxy}benzyl)-3 - triphenyltetrazolium-2,4-dione (obtained as described in obtaining 55) and 36 ml of a mixture (3:1 by volume) of acetic acid and water, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture (1:3 by volume) hexane and ethyl acetate, and the resulting received 450 mg specified in the title compound, melting at 189-191oC.

Example 22. 5-{4-(6-Bromo-3-methylimidazo[5,4-b]pyridine - 2-ylethoxy)-benzyl}thiazolidine-2,4-dione (Compound N 1-137).

Repeated p is imidazo[5,4-b] pyridine-2-ylethoxy)benzyl}-3 - triphenyltetrazolium-2,4-dione (obtained, as described in obtaining 60) and 40 ml of a mixture (3:1 by volume) of acetic acid and water, and the result was indicated in the title compound as crude product. This crude product was vykristallizovyvalas rubbing with ethyl acetate, resulting in a 1.75 g specified in the title compound, melting at 204-205oC.

Example. 23. 5-{4-(6-Chloro-3-methylimidazo[5,4-b]pyridine - 2-ylethoxy)-benzyl}thiazolidine-2,4-dione (Compound 1-140 N).

Repeating a similar procedure to that described in example 12, except that the used of 1.40 g of 5-{4-(6-chloro-3-methylimidazo[5,4-b] pyridine-2-ylethoxy)benzyl}-3 - triphenyltetrazolium-2,4-dione (obtained as described in getting 65) and 20 ml of a mixture (3:1 by volume) of acetic acid and water, and the result was indicated in the title compound as crude product. This crude product was vykristallizovyvalas with rubbing with ethyl acetate, resulting in 0.75 g specified in the title compound, melting at 203-205oC.

Example 24. 5-{4-(5-Methoxy-3-methylimidazo[5,4-b]pyridine - 2-ylethoxy)-benzyl}thiazolidine-2,4-dione (Compound N 1-142) and its hydrochloride and fumarate.

1) Repeated a similar procedure to that opei)benzyl} -3 - triphenyltetrazolium-2,4-dione (obtained, as described in obtaining 70) and 10 ml of a mixture (3:1 in volume) of acetic acid and water, and the result was indicated in the title compound as crude product. This crude product was vykristallizovyvalas rubbing with ethyl acetate, resulting in 325 mg specified in the title compound, melting at 258-260oC.

2) To 6 ml of 4 n solution of hydrogen chloride in ethyl acetate was added 100 mg of 5-{ 4-(5-methoxy-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl} thiazolidine-2,4-dione [obtained as described above, at the stage (I)], and the resulting mixture was treated with ultrasound for 30 minutes At the end of this time the resulting crystals were collected by filtration and dried by evaporation under reduced pressure, resulting in an 87 mg of the hydrochloride specified in 5 the title compound, melting at 255-262oC.

3) In 30 ml of methanol was dissolved 100 mg of 5-{4-(5-methoxy-3 - methylimidazo[5,4-b] pyridine-2-ylethoxy)benzyl} thiazolidine-2,4-dione [obtained as described above, at the stage (I)], and to the resulting solution was added 29 mg of fumaric acid. The resulting mixture was treated with ultrasound for 30 minutes At the end of this time the solvent was removed by distillation under ponish ethanol Polysorbate fumarata, specified in the title compound, melting at 245 - 253oC.

Example 25. 5-{4-(1-Methylimidazo[4,5-c]pyridine-2-ylethoxy)benzyl} thiazolidine-2,4-dione (Compound N 1-156).

Repeating a similar procedure to that described in example 12, except that used 3,40 g of 5-{4-(1-methylimidazo [4,5-C]pyridine-2-ylethoxy)benzyl} -3-triphenyltetrazolium-2,4 - dione (obtained as described in getting 74) and 24 ml of a mixture (3:1 by volume) of acetic acid and water, and the result was indicated in the title compound as crude product. This crude product was vykristallizovyvalas rubbing with ethyl acetate, resulting in 1.01 g specified in the title compound, melting at 264-265oC.

Example 26. 5-[4-(1-Methyl-7-azaindole-2 - ylethoxy)benzyl]-thiazolidine-2,4-dione (Compound 1-81 N).

Repeating a similar procedure to that described in example 12, except that the reaction was carried out using 270 mg of 5-[4-(1-methyl-7-azaindole-2-ylethoxy)benzyl]-3-triphenyltetrazolium - 2,4-dione (obtained as described in getting 82) and 3 ml of a mixture (2:1:3 by volume) acetic acid, water and 1,4-dioxane. After the expiration of the allotted reaction time, the reaction clamatory through silica gel, using a mixture (1:1 by volume) hexane and ethyl acetate as eluent, and the result was 157 mg specified in the title compound, melting at 183-185oC.

Example 27. 5-{4-(3-Phenylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl}- thiazolidine-2,4-dione (Compound N 1-161).

Repeating a similar procedure to that described in example 18, except that used 2,78 g 3-amino-2-phenylaminopyrimidine (obtained as described in getting 84), 3.98 g of 5-[4-(2-oksidoksi)benzyl] thiazolidin-2,4-dione (obtained as described in obtaining 47), 4.9 g of iodine, 6 ml of ethanol, 6 ml of acetic acid and 50 ml of 1,2-dimethoxyethane. After processing the product as described in example 18, the crude product was purified by column chromatography through silica gel, using as eluent a mixture (1:2 by volume) hexane and ethyl acetate, and the resulting received 400 mg specified in the title compound, melting at 88-91oC.

Example 28. 5-{4-(3,5,7-Trimethylimidazo[5,4-b]pyridine-2-ylethoxy)- benzyl}thiazolidine-2,4-dione (Compound N 1-218) and his triptorelin.

Repeating a similar procedure to that described in example 2, except that used 3.5 g of 5-{4-(3,5,7-trimethylamine 87), 100 ml of methylene chloride and 20 ml triperoxonane acid. After the allotted reaction time, the reaction mixture was freed from methylene chloride and triperoxonane acid by distillation under reduced pressure. The resulting crude product is recrystallized from a mixture of ethyl acetate and hexane, which gave 2.4 g of triptoreline specified in the title compound, melting at 226-228oC.

Triptorelin (2.3 g) obtained as described above, suspended in a mixture of ethyl acetate (50 ml) and aqueous sodium hydrogen carbonate solution (50 ml), and the suspension was stirred at room temperature for 30 minutes At the end of this period the precipitated crystals were collected by filtration and washed with water, and then dried under reduced pressure, resulting in 1.47 g specified in the title compound, melting at 229-230oC.

Example 29. 5-{ 4-(3-Methyl-5-phenylthioureido[5,4-b] pyridine-2 - ylethoxy)benzyl}thiazolidine-2,4-dione (Compound N 1-177).

Repeating a similar procedure to that described in example 12, except that 1,58 g of 5-{4-(3-methyl-5-phenylthioureido [5,4-b]pyridine-2-ylethoxy)benzyl}-3-triphenyltetrazolium-2,4 - dione (obtained as about the AK, as described in example 12, the crude product was vykristallizovyvalas rubbing with ethyl acetate, and the result was 1,02 g specified in the title compound, melting at 166-168oC.

Example 30. 5-{4-(5-Benzyloxy-3-methylimidazo[5,4-b]pyridine - 2-ylethoxy)benzyl}thiazolidine-2,4-dione (Compound N 1-207).

Repeating a similar procedure to that described in example 12, except that of 1.00 g of 5-{4-(5-benzyloxy-3-methylimidazo [5,4-b]pyridine-2-ylethoxy)benzyl} -3-triphenyltetrazolium-2,4 - dione (obtained as described in obtaining 95) was treated with 12 ml of a mixture (3:1 by volume) of acetic acid and water. After processing the product as described in example 12, the crude product was vykristallizovyvalas rubbing with ethyl acetate, gave 0,63 g specified in the title compound, melting at 210-211oC.

Example 31. [5-{ 4-(5-Hydroxy-3-methylimidazo[5,4 - b]pyridine-2-ylethoxy)-benzyl}thiazolidine-2,4-dione (Compound N 1-153).

Repeating a similar procedure to that described in example 6, except that used 1.20 g of 5-{ 4-(5-benzyloxy-3-methylimidazo[5,4-b] pyridine-2-ylethoxy)benzyl} -3-triphenyltetrazolium-2,4-dione (obtained as described in raffia through silica gel, using the method of gradient elution with mixtures of ethyl acetate and methanol in ratios from 1:0 to 10:1 by volume as the eluent, and the result was obtained 0.10 g specified in the title compound, melting at 240-242oC.

Example 32. 5-{4-(5-Ethoxy-3-methylimidazo[5,4-b]pyridine-2-ylethoxy) benzyl}thiazolidine-2,4-dione (Compound N 1-182).

Repeating a similar procedure to that described in example 12, except that of 2.75 g of 5-{4-(5-ethoxy-3-methylimidazo[5,4-b]pyridine-2 - ylethoxy)benzyl} -3-triphenyltetrazolium-2,4-dione (obtained as described in getting 99) was treated with 24 ml of a mixture (3:1 by volume) of acetic acid and water. After processing the product as described in example 12, the crude product was vykristallizovyvalas rubbing with ethyl acetate, gave the result of 1.57 g specified in the title compound, melting at 245-246oC.

Example 33. 5-{ 4-(5-Isopropoxy-3-methylimidazo[5,4 - b]pyridine-2-ylethoxy)benzyl}thiazolidine-2,4-dione (Compound N 1-183).

Repeating a similar procedure to that described in example 12, except that 0,78 g of 5-{4-(5-isopropoxy-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl} - 3-triphenyltetrazolium-2,4-dione (poluchennoy product, as described in example 12, the crude product was led by rubbing with ethyl acetate, resulting in 0.40 g specified in the title compound, melting at 210-212oC.

Example 34. 5-{4-[2-(3-Methylimidazo[5,4-b]pyridine-2-yl)- ethoxy)benzyl} thiazolidine-2,4-dione (Compound N 1-190).

Repeating a similar procedure to that described in example 18, except that he used to 0.94 g of 3-amino-2-methylaminopropane (obtained as described in getting 105), 2.10 g of 5-[4-(3-oxopropoxy)benzyl] thiazolidin-2,4-dione (obtained as described in getting 107), 6 ml of ethanol, 3 ml of acetic acid, 2,32 g of iodine and 30 ml of 1,2-dimethoxyethane. After processing the product as described in example 18, the crude product was purified by column chromatography through silica gel, using as eluent ethyl acetate, and the result was 85 mg specified in the title compound, melting at 96-100oC.

Example 35. 5-{ 4-(3-Methyl-5-phenylimidazo[5,4-b] pyridine - 2-ylethoxy)benzyl}thiazolidine-2,4-dione. (Compound N 1-179).

Repeating a similar procedure to that described in example 12, except that 0.9 g of 5-{4-(3-methyl-5-phenylimidazo [5,4-b]pyridine-2-ylethoxy)bi (3:1 by volume) of acetic acid and water. After processing the product as described in example 12, the resulting crude product was led by trituration with ethyl acetate, gave 420 mg specified in the title compound, melting at 211-213oC.

Example 36. 5-{4-(3-Methylimidazo[5,4-b]pyridine-2-ylethoxy)- benzylidene} thiazolidin-2,4-dione (Compound N 2-100).

A mixture of 0.35 g of 2-(4-formylphenoxy)-3-methylimidazo[5,4 - b]pyridine (obtained as described in getting 112), 0.31 g of 2,4-thiazolidinedione, of 0.26 ml of piperidine and 10 ml of ethanol was heated under reflux for 4 hours At the end of this time the solvent was removed by distillation under reduced pressure, and the residue was led by rubbing with water. The crystals were collected by filtration and washed with water and then with ethyl acetate, resulting in 0,38 g specified in the title compound, melting at 279-281oC.

Obtaining 1. Ethylindole-2-carboxylate.

A mixture of 25.2 g of indoline-2-carboxylic acid, 50 ml of ethanol and 200 ml of 4 n solution of hydrogen chloride in dioxane was stirred at room temperature for 3 days. At the end of this time the reaction mixture was poured into aqueous potassium carbonate solution, and then was extracted with ethyl acetate. Eitel by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel, using as eluent a mixture (2:1 by volume) hexane and ethyl acetate, and as a result got to 28.1 g specified in the header of the compounds having Rf= 0,81 (thin layer chromatography on silica gel using a mixture (2:1 by volume) hexane and ethyl acetate as developing solvent).

Getting 2. Indolin-2-ylmethanol.

To a mixture of 1.20 g of sociallyengaged and 80 ml of anhydrous tetrahydrofuran was added dropwise (under ice cooling) solution 5,12 g ethylindole-2-carboxylate (obtained as described in obtaining 1) in 20 ml of anhydrous tetrahydrofuran, and the resulting mixture was stirred at room temperature for 2 hours thereafter, to the mixture was added excess decahydrate sodium sulfate, after which the resulting mixture was stirred 20 minutes At the end of this time was filtered, the insoluble materials and the filtrate was concentrated by evaporation under reduced pressure. The concentrate was purified by column chromatography through silica gel, using as eluent a mixture (3: 1 by volume) hexane and ethyl acetate, and the result was 3,81 g specified in the header by volume) hexane and ethyl acetate as developing solvent).

Getting 3. 1-tert-Butoxycarbonyl-2-hydroxymethylcytosine.

To a solution of 4.0 g of indolin-2-ylmethanol (obtained as described in obtaining 2) and 3.8 ml of triethylamine in 40 ml of anhydrous tetrahydrofuran was added dropwise to 6.2 ml t-tertbutylamine, and the resulting mixture was stirred at room temperature for 10 hours At the end of this time the reaction mixture was poured into water, then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. Then solvent was removed by distillation under reduced pressure, and the obtained residue was purified by column chromatography through silica gel, using as eluent a mixture (5:1 by volume) hexane and ethyl acetate, resulting in got to 5.57 g specified in the header of the compounds having Rf= 0,46 (thin-layer chromatography on silica gel using a mixture of hexane and ethyl acetate with the ratio of 2:1 by volume) as developing solvent).

Getting 4. 5-[4-(1-tert-Butoxycarbonylamino-2-ylethoxy)benzyl] - 3-triphenyltetrazolium-2,4-dione.

To a mixture of 6.5 g of 1-tert-butoxycarbonyl-2-hydroxymethyl-indoline (obtained as on the frame so that as described in the publication N A European patent) and 100 ml of anhydrous tetrahydrofuran was added dropwise a solution of 6.6 g of 1,1'-(azodicarbon)piperidine in 10 ml of anhydrous tetrahydrofuran and 20 ml of anhydrous dimethylformamide, and the resulting mixture was stirred at room temperature for about 20 hours At the end of this time was filtered, the insoluble materials and the filtrate was concentrated by evaporation under reduced pressure. the concentrate was purified by column chromatography through silica gel, using as eluent a mixture (10:1 by volume) hexane and ethyl acetate, giving 3,70 g specified in the title compound, melting at 85,4-87,2oC.

Getting 5. Methyl-1-methylindolin-2-carboxylate.

To a mixture of 10.3 g ()-indolin-2-carboxylic acid, 200 ml of dimethylformamide and 25.4 g of anhydrous potassium carbonate was added dropwise to 11.7 ml under the conditions, and the resulting mixture was stirred at room temperature for 3 hours after this time the reaction mixture was poured into water, then was extracted with her with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. Then solvent was removed othona the aqel, using as eluent a mixture of hexane and ethyl acetate with the ratio of 7:1 by volume, resulting in a received 9,12 g specified in the header of the compounds having Rf= 0,77 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate to 2:1 by volume).

Getting 6. 1-Methylindolin-2-ylmethanol.

Repeating a similar procedure to that described in the getting 2, except that used 8.0 g of methyl-1-methylindolin-2-carboxylate (obtained as described in obtaining 5), 1.91 sociallyengaged and 250 ml of tetrahydrofuran, and the result was 6.85 g specified in the header of the compounds having Rf= 0,35 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate to 2:1 by volume).

Getting 7. 5-[4-(1-Methylindolin-2-ylethoxy)benzyl] -3-triphenyl-methylthiazolidine-2,4-dione.

Repeating a similar procedure to that described in the getting 5, except that used 2.0 g of 1-methylindolin-2-ylmethanol (obtained as described in obtaining 6), to 4.73 g of 5-(4-hydroxybenzyl)-3-triphenylmethyl TIA is Chile 4,39 g specified in the connection header, melting at 62,5-65,5oC.

Getting 8. Methylindolin-1-ylacetic.

To a mixture of 0.25 g indoline, 2 ml of dimethylformamide and 0.87 g of anhydrous potassium carbonate was added dropwise to 0.40 ml methylpropanoate, and the resulting mixture was stirred at room temperature for 1 h after this time the reaction mixture was poured into water, then was extracted with her with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. Solvent was removed by distillation under reduced pressure, and the obtained residue was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate with a ratio of 5:1 by volume, resulting in learned of 0.30 g specified in the header of the compounds having Rf= 0,63 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate to 2:1 by volume).

9. 2-(Indolin-1-yl) ethanol.

Repeating a similar procedure to that described in the getting 2, except that used 780 mg of methyl-indolin-1-ilaclama (obtained as described in obtaining 8), 200 m is ke connection with Rf= 0,31 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate to 2:1 by volume).

Getting 10. 5-{4-[2-(Indolin-1-yl)ethoxy]benzyl}-3-triphenylmethyl-thiazolidin-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 240 mg of 2-(indolin-1-yl)ethanol (obtained as described in 9), 690 mg of 5-(4-hydroxybenzyl)-3-triphenylmethyl-thiazolidin-2,4-dione, and 0.37 ml of tributylphosphine, 370 mg of 1,11(azodicarbon)-piperidine and 5 ml of anhydrous tetrahydrofuran, and the result was 530 mg specified in the header of the compounds having Rf= 0,88 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate to 2: 1 by volume).

Getting 11. 5-{4-[2-(Indol-3-yl)ethoxy]benzyl}-3 - triphenylmethyl-thiazolidin-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 5.0 g of 2-(indol-3-yl)ethanol of 14.4 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 7,73 ml tributylphosphine, 7,83 g of 1,1'-(azodicarbon)depypere 81,0-82,5oC.

Getting 12. Methylindol-1-ylacetic.

To a mixture of 2.0 g of sodium hydride (as a 55% by weight dispersion in mineral oil, and pre-washed with hexane) and 80 ml of dimethylformamide was added dropwise (cooling with ice) solution of 5.0 g of indole in 20 ml of dimethylformamide, and the resulting mixture was stirred at room temperature for 1 h On the end of that time was added dropwise to 4.5 ml of methylpropanoate (ice cooling), then the mixture was stirred at room temperature for 2 hours After completion of mixing within the specified time, the reaction mixture was poured into ice water and then extracted it with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. Then solvent was removed by distillation under reduced pressure, and the obtained residue was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate with the ratio of 10:1 by volume), giving the result of 6.52 g specified in the header of the compounds having Rf= 0,66 (thin-layer chromatography on silica gel using as developing solvent a mixture of Huck and procedure similar to that described in the getting 2, except that used 6.20 g of methyl-indol-1-ilaclama (obtained as described in obtaining 12), 1.50 g of sociallyengaged and 220 ml of anhydrous tetrahydrofuran, and as a result got a 5.25 g specified in the header of the compounds having Rf= 0,33 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate to 2:1 by volume).

Getting 14. 5-{4-[2-(Indol-1-yl)ethoxy]benzyl}-3-triphenylmethyl - thiazolidin-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 2.0 g of 2-(indol-1-yl) ethanol (obtained as described in 13), to 4.81 g of 5-(4-hydroxybenzyl)-3-triphenylmethyl-thiazolidin-2,4-dione, 3,1 ml tributylphosphine, 3,20 g of 1,1'-(azodicarbon)-dipiperidino and 60 ml of anhydrous benzene, and the resulting received 5.69 g specified in the connection header, melting at 63,5-65,9oC.

Get 15. 3 Methylimidazo[5,4-b]pyridine-2-ylmethanol.

To a mixture of 0.98 g of sodium hydride (as a 55% by weight dispersion in mineral oil, and pre-washed with hexane) and 100 ml of dimethylformamide dobavljal, then to the mixture was added 3.51 g under the conditions (under ice cooling). After that, the mixture was stirred 15 hours At the end of this time the reaction mixture was freed from dimethylformamide by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using the method of gradient elution with mixtures of ethyl acetate and ethanol with the ratio from 1:0 to 10:1 by volume as the eluent, and the result was obtained 1.7 g specified in the title compound, melting at 229-231oC.

Getting 16. 5-{4-(3-Methylimidazo[5,4-b] pyridine-2-ylethoxy)benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 0.5 g of 3-methylimidazo[5,4-b]pyridine-2-ylmethanol (obtained as described in obtaining 15), 1,43 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, or 0.83 ml tributylphosphine, 0,773 g of 1,1'-(azodicarbon)dipiperidino and 80 ml of benzene, and the result was 0.3 g specified in the title compound, melting at 97-102oC.

Getting 17. Methyl-7-azaindole-1-acetate.

Repeating a similar procedure to that described in obtaining 12, 5 g of 7-azaindole, 100 ml of dimethylformamide and 4.2 ml of methylpropanoate, and as a result received of 7.70 g specified in the header of the compounds having Rf= 0,33 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate to 2:1 by volume).

Getting 18. 2-(7-Isoindol-1-yl)ethanol.

Repeating a similar procedure to that described in the getting 2, except that used 7.50 g of methyl-7-azaindole-1-acetate (obtained as described in obtaining 17), 1,80 g sociallyengaged and 260 ml without water tetrahydrofuran, and as a result got to 5.57 g specified in the title compound, melting at 52,7-53,3oC.

Getting 19. 5-{ 4-[2-(7-Isoindol-1-yl)ethoxy]benzyl}-3 - triphenyl-methylthiazolidine-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that he used to 1.77 g of 2-(7-isoindol-1-yl)ethanol (obtained as described in obtaining 18), and 4.40 g of 5-(4-hydroxybenzyl)- 3-triphenyltetrazolium-2,4-dione, 2.35 ml of tributylphosphine, 2,39 g of 1,1'-(azodicarbon)dipiperidino and 45 ml of anhydrous benzene, and the result was 4,58 g specified in the title compound, melting at 167,5-168,9ridin-2-carboxylate [described in J. Org. Chem., 30, 2403-2407 (1965)] in 200 ml of tetrahydrofuran was added at room temperature 3,68 g of lithium borohydride, and then to the mixture was added dropwise 20 ml of methanol, after which the mixture was allowed to stand all night lie to room temperature. At the end of this time the reaction mixture was diluted with 10 ml of water and then concentrated by evaporation under reduced pressure. The concentrate was mixed with an aqueous solution of sodium chloride, after which it was extracted it with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The obtained residue was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and ethanol with the ratio of 5:1 by volume. The resulting product was recrystallized from a mixture of ethyl acetate and hexane, which gave the result of 0.56 g specified in the title compound, melting at 126-128oC.

Getting 21. 5-{ 4-(Imidazo[1,2-a]pyridine-2 - ylethoxy)benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 920 mg imidazo[1,2-a]pyridine-2-ylmethanol (obtained as described in obtaining 20L)dipiperidino and 60 ml of benzene, and the result was 3.1 g specified in the header of the compounds having Rf= 0,71 (thin-layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and ethanol with the ratio of 10:1 by volume).

Getting 22. Methyl/1-methylindol-2-carboxylate.

To a mixture of 5.00 g of indole-2-carboxylic acid, 100 ml of dimethylformamide and 13.0 g of anhydrous potassium carbonate was added dropwise to 6.0 ml under the conditions, and the resulting mixture was stirred at 100oC for 6 hours At the end of this time the reaction mixture was treated by following the procedure described in the getting 5, and got the result 5,12 g specified in the title compound, melting at 91,3-92,8oC.

23. 1-Methylindol-2-ylmethanol.

To a mixture of 1.85 g of lithium borohydride and 80 ml of anhydrous tetrahydrofuran was added dropwise a solution of 5.05 g of methyl-1-methylindol-2-carboxylate (obtained as described in obtaining 22) in 20 ml of anhydrous tetrahydrofuran, and the resulting mixture was heated under reflux for 4 hours after this time the reaction mixture was poured into water, and then extracted it with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and OEM, receiving 4,30 g specified in the title compound, melting at 92,8-95,2oC.

Getting 24. 5-[4-(1-Methylindol-2-ylethoxy)benzyl]-3 - triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 4,30 g 1-methylindol-2-ylmethanol (obtained as described in obtaining 23), 10.3 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 6,65 ml tributylphosphine, of 6.73 g of 1,1'-azodicarbon)dipiperidino and 120 ml of benzene, and the result was 6,28 g specified in the title compound, melting at 134,3-136,0oC.

Getting 25. Ethylimidazole[1,2-a]pyridine-2-ylacetic.

A solution of 14.6 g of 2-aminopyridine and 25.5 g of ethyl-4-chloro of acetoacetate in 200 ml of acetonitrile was heated under reflux in the course of 14.5 hours At the end of this time the reaction mixture was freed from solvent by distillation under reduced pressure. The residue was mixed with an aqueous solution of potassium carbonate, and then was extracted with a mixture of ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced d the e eluent, and the result was 2.65 g specified in the header of the compounds having Rf= 0,33 (thin-layer chromatography on silica gel using ethyl acetate as the developing solvent).

Getting 26. 2-(2-Hydroxyethyl)imidazo[1,2-a]pyridine.

Repeating a similar procedure to that described in the getting 2, except that used to 2.65 g ethylimidazole[1,2-a]pyridine-2-ilaclama (obtained as described in getting 25), 0.5 g of sociallyengaged and 100 ml of tetrahydrofuran, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel; using the method of gradient elution with mixtures of ethyl acetate and ethanol in ratios from 20:1 to 4:1 by volume as the eluent, and as a result got 1,32 g specified in the title compound, melting at to 120.3-126,9oC.

Getting 27. 5-{ 4-[2-(Imidazo[1,2-a] pyridine-2-yl)ethoxy} benzyl]-3 - triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that he used to 0.80 g of 2-(2-hydroxyethyl)imidazo [1,2-a]pyridine (obtained as described in carbonyl)piperidine and 30 ml of benzene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution, using as eluent a mixture of hexane and ethyl acetate in ratios from 1:4 to 0.1 by volume, and the result was 0.97 g specified in the title compound, melting at 135,5-142,4oC (decomposition).

Getting 28. 3-Ethyl-2-hydroxymethylimidazole[5,4-b]pyridine.

To a suspension of 0.87 g of sodium hydride (as a 55% by weight dispersion in mineral oil, and pre-washed with hexane) in 80 ml of dimethylformamide was added 3 g of 2-hydroxymethyl-3H - imidazo[5,4-b]pyridine, and the resulting mixture was stirred at room temperature for 2 hours thereafter, to the mixture was added dropwise 1,78 ml ethyliodide (ice cooling), and the resulting mixture was stirred at room temperature for 2 h, then allowed it to stand over night. At the end of this period the reaction mixture was freed from dimethylformamide by distillation under reduced pressure. The residue was purified by column chromatography through silica gel by the method of gradient elution, using as eluent serpents connection melting at 117-121oC.

Getting 29. 5-{4-(3-Ethylimidazole[5,4-b]pyridine-2-ylethoxy)benzyl} -3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 0.5 g of 3-ethyl-2-hydroxymethylimidazole[5,4-b] ] pyridine (obtained as described in obtaining 28), 1,313 g of 5-(4-hydroxybenzyl)-3 - triphenyltetrazolium-2,4-dione, of 0.77 ml tributylphosphine, 0,712 g of 1,1'-(azodicarbon)dipiperidino and 80 ml of benzene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:3 by volume, and received the 300 mg specified in the header of the compounds having Rf= 0,55 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio of 1:3 by volume).

30. 2-Hydroxymethyl-1-methylimidazo[4,5-b]pyridine.

Repeating a similar procedure to that described in obtaining 15, except that used 45 g of 2-hydroxymethyl-3H-imidazo[5,4-b] pyridine, 1 the amide, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution, using as eluent a mixture of ethyl acetate and methanol in ratios from 1:0 to 1:1 by volume, and received 3,24 g specified in the title compound, melting at 130-132oC.

Getting 31. 5-{ 4-(1-Methylimidazo[4,5-b]pyridine-2 - ylethoxy)benzyl} triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 2.5 g of 2-hydroxymethyl-1-methylimidazo[4,5-b] pyridine (obtained as described in obtaining 30), 6.5 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium - 2,4-dione, 3,47 ml tributylphosphine, to 3.52 g of 1,1'-(azodicarbon)dipiperidino and 200 ml of 1,4-dioxane, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in ratios from 1:1 to 0:1 by volume) and then with mixtures of ethyl acetate and methanol in ratios from 20:1 to 10:1 by Aya acid.

To a solution of 10.0 g-butyrolactone in 100 ml of methanol was added 2 N. aqueous sodium hydroxide solution, and the mixture was allowed to stand overnight. After the reaction mixture was neutralized by adding 2 N. aqueous solution of hydrochloric acid, then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. Then solvent was removed by distillation under reduced pressure, resulting in 3,70 g specified in the connection header in the form of butter.

Receiving 33. 2-(3-Hydroxypropyl)-3H-imidazo[5,4-b]pyridine.

To 0,77 g of 2,3-diaminopyridine added 0,83 g of 4 - hydroxybutiric acid (obtained as described in obtaining 32), and the resulting mixture was stirred at 150oC for 4 h At the end of this time the reaction mixture was treated with 3 N. aqueous hydrochloric acid and then selecively the addition of an aqueous ammonia solution. The aqueous mixture was evaporated to dryness under reduced pressure, and then the obtained residue was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the ratio of 5:1 by volume. The product has led races is P>o
C.

Getting 34. 2-(3-Hydroxypropyl)-3-methylimidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 15, except that used 3,40 g of 2-(3-hydroxypropyl)-3H-imidazo[5,4-b] pyridine (obtained as described in obtaining 33), 0,81 g of sodium hydride (50% in weight dispersion in mineral oil, 1.2 ml under the conditions and 100 ml of dimethylformamide, and the result was indicated in the title compound as crude product. This crude product was cleaned by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the ratio of 10:1 by volume. The product was led by rubbing with ethyl acetate, which resulted in 3,10 g specified in the title compound, melting at more than 300oC.

Getting 35. 5-[4-{3-(3-Methylimidazo[5,4-b]pyridine-2 - yl)propoxy}-benzyl]-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 750 mg of 2-(3-hydroxypropyl)-3 - methylimidazo[5,4-b] pyridine (obtained as described in obtaining 34) and 1.83 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium - 2,4-dione, and 0.98 ml of a tribe connection in the form of a crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in ratios from 1:1 to 0:1 by volume, which gave 550 mg specified in the title compound, melting at 76-81oC.

Getting 36. Methyl-4-nitrophenoxyacetic.

A solution of 56 g of 4-NITROPHENOL, 90 g of methylpropanoate and 100 g of potassium carbonate in 500 ml of dimethylformamide was stirred at room temperature for 2 days. At the end of this time the reaction mixture was freed from dimethylformamide by distillation under reduced pressure. The residue was diluted with water, then was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The obtained residue was led by rubbing with hexane, resulting in a 63.3 g specified in the title compound, melting at 98-99oC.

Getting 37. Methyl-4-aminophenoxyethanol.

Repeating a similar procedure to that described in example 6, except that used 30,8 g methyl-4-nitrophenoxyacetic of 25.8 g specified in the connection header, with Rf= 0,79 (thin-layer chromatography on silica gel using ethyl acetate as the developing solvent).

Getting 38. Methyl-4-(2-bromo-2-butoxycarbonylmethyl)phenoxyacetate.

To a solution of 25.8 g of methyl-4-aminophenoxyethanol (obtained as described in obtaining 37), in 263 ml of a mixture (2:5 by volume) of methanol and acetone was added dropwise (under ice cooling) 98 g of 47% (m/o) aqueous Hydrobromic acid and then 33 ml of an aqueous solution containing 12.8 g of sodium nitrite, and the resulting mixture was stirred 30 min, cooling with ice. Then to the mixture was added 18.2 g of butyl acrylate. Stirred the mixture for 30 minutes while cooling with ice, after which was added 3.2 g of copper bromide (I), and the resulting mixture was stirred overnight at room temperature. Then the reaction mixture was freed from solvent by distillation under reduced pressure. The residue was diluted aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure, resulting in at 51.7 g of the crude product containing the specified header connection and had Rf= 0,46 (thin-layer chromatography on silica gel with ptx2">

Getting 39. 5-[4-(Ethoxycarbonylmethoxy)benzyl]-thiazolidine-2,4-dione.

A solution of 100 g of methyl-4-(2-bromo-2-butoxycarbonylmethyl)-phenoxyacetate (obtained as described in obtaining 38) and 22 g of thiourea in 200 ml of ethanol was heated under reflux for 2.5 hours thereafter, to the mixture was added 2 N. aqueous solution of hydrochloric acid, and the resulting mixture was heated under reflux 5 hours At the end of this time the reaction mixture was freed from solvent by distillation under reduced pressure. The obtained residue was diluted with water, then was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The obtained residue was purified by column chromatography through silica gel, using as eluent a mixture (2: 5 by volume) of ethyl acetate and hexane, and as a result got to 19.4 g specified in the title compound, melting at 105-106oC.

Getting 40. 3,7-Dimethyl-2-hydroxymethylimidazole[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 15, except that he used to 5.00 g of 2-hydroxymethyl-2-methyl - 3H-imidazo[5,4-b] pyridine, 1,34 g Ki is the result received is listed in the title compound as crude product. This crude product was purified by column chromatography by the method of gradient elution using as eluent mixtures of ethyl acetate and methanol in ratios from 1:0 to 10:1 by volume, which resulted in 4.4 g specified in the title compound, melting at more than 300oC.

Getting 41. 5-{ 4-(3,7-Dimethylimidazo[5,4-b] pyridine-2 - ylethoxy)-benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 1.50 g of 3,7-dimethyl-2-hydroxymethylimidazole[5,4-b] pyridine (obtained as described in obtaining 40), 3,34 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 2,11 ml tributylphosphine, 2.14 g of 1,1'-(azodicarbon)piperidine and 30 ml of toluene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in the ratio from 1:1 to 1:2 by volume, which resulted in 1,11 g specified in the title compound, melting at 92-105oC (softening).

Getting 42. 6-Chloro-2,3-dia is 1 by volume) of ethyl acetate and 2-methyl-2-propanol was stirred at 60oC for one hour, after which was added to 1.32 g of sodium borohydride at 60oC, and the mixture was stirred at this temperature for 3 hours after this time the reaction mixture was freed from solvent by distillation under reduced pressure. The obtained residue was diluted with water and neutralized by addition of an aqueous potassium carbonate solution, and then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was led by rubbing with a mixture of ethyl acetate and hexane, resulting in 6.50 g specified in the title compound, melting at 120-122oC.

Getting 43. 5-Chloro-2-hydroxymethyl-3H-imidazo[5,4-b]pyridine.

To 5,00 g of 6-chloro-2,3-diaminopyridine (obtained as described in obtaining 42) was added 6.60 g of glycolic acid, and the resulting mixture was stirred at 150oC for 4 h At the end of this time the reaction mixture was treated with 3 N. aqueous solution of hydrochloric acid and then selecively the addition of an aqueous ammonia solution, suitable mixture was evaporated to dryness, and the Oia using as eluent mixtures of ethyl acetate and methanol in the ratio of from 1:0 to 10:1 by volume. The resulting product was then led by rubbing with ethyl acetate, resulting in 5,33 g specified in the title compound, melting at 224-226oC.

Getting 44. 5-Chloro-2-hydroxymethyl-3-methylimidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 15, except that he used to 3.00 g of 5-chloro-2-hydroxymethyl-3H-imidazo[5,4-b]pyridine (obtained as described in obtaining 43), 0.71 g of sodium hydride (as a 55% by weight dispersion in mineral oil, 1.1 ml under the conditions and 70 ml of dimethylformamide, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of ethyl acetate and methanol in the ratio of from 1:0 to 10:1 by volume, which gave 1,60 g specified in the title compound, melting at 204 - 210oC.

Getting 45. 5-{4-(5-Chloro-3-methylimidazo[5,4-b]pyridine - 2-ylethoxy)-benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 1.20 g of 5-chloro-2-hydroxymethyl-3-metabolizing-2,4-dione, 1,51 ml tributylphosphine, 1,53 g of 1,1'-(azodicarbon)dipiperidino and 25 ml of toluene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in the ratio from 2:1 to 1:1 by volume, which resulted in 1.29 g specified in the title compound, melting at 97-99oC (softening).

Getting 46. 5-[4-(2,2-Diethoxyethane)benzyl]thiazolidin-2,4-dione.

To a suspension of 260 mg of sodium hydride (as a 55% by weight dispersion in mineral oil, and pre-washed with toluene) in 5 ml of dimethylformamide was added under ice cooling) 530 mg of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione, and the mixture was stirred at room temperature for 30 minutes By the end of that time, to the mixture was added with ice cooling) to 0.73 ml diethylacetal of bromoacetaldehyde, and the resulting mixture was stirred at 50oC for 3 hours By distillation under reduced pressure was released, the reaction mixture from dimethylformamide. The obtained residue was diluted with water and the aqueous mixture was adjusted to pH 2 to the act was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, then solvent was removed by distillation under reduced pressure. The obtained residue was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio 2:1 by volume, receiving 600 mg specified in the header of the compounds having Rf= 0,46 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio 2:1 by volume).

Getting 47. 5-[4-(2-Oksidoksi)benzyl]thiazolidin-2,4-dione.

To a solution of 10,07 g of 5-[4-(2,2-diethoxyethane)benzyl]- thiazolidine-2,4-dione (obtained as described in obtaining 46) in 80 ml of tetrahydrofuran was added 20 ml of 6 N. aqueous solution of hydrochloric acid, and the mixture was allowed to stand overnight at room temperature. At the end of this period the reaction mixture was freed from solvent by distillation under reduced pressure. The residue was diluted with water, then was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and solvent was removed by distillation under reduced pressure. The obtained residue was purified by column chromatography through silikagelyakh in the title compound, with Rf= 0,37 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio of 1:2 by volume).

Receive 48. 2-Hydroxymethyl-3H-imidazo[5,4-b]pyrimidine.

To 2,27 g 4:5-diaminopirimidina added 8,58 g ethyl-glycolate, and the resulting mixture was stirred at 140oC for 2 hours after this time the reaction mixture was freed from ethylglycol by distillation under reduced pressure. The residue was decolorized with activated carbon and was led by rubbing with ethanol, resulting in 1,81 g specified in the header of the compounds having Rf= 0,27 (thin-layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and methanol in the ratio of 10:1 by volume).

Getting 49. 2-tert-Butyldimethylsilyloxy - 3H-imidazo[5,4-d]pyrimidine.

A mixture of 1.81 g of 2-hydroxymethyl-3H-imidazo[5,4-d]pyrimidine (obtained as described in obtaining 48), 2,71 g of tert-butyldimethylsilyloxy, of 2.45 g of imidazole and 100 ml of dimethylformamide was stirred at room temperature for 1 h, after this time the reaction messadie water, then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The obtained residue was purified by column chromatography through silica gel, using ethyl acetate as eluent, which resulted in 1,89 g specified in the title compound, melting at 104-107oC.

Getting 50. 2-Hydroxymethyl-3-methylimidazo[5,4-d]pyrimidine.

Repeating a similar procedure to that described in obtaining 15, except that used 1,89 g of 2-tert-butyldimethylsilyloxy-3H-imidazo[5,4-d] pyrimidine (obtained as described in obtaining 49), and 0.37 g of sodium hydride (as a 55% by weight dispersion in mineral oil), 490 μl under the conditions and 30 ml of dimethylformamide. After this time the reaction mixture was freed from dimethylformamide by distillation under reduced pressure. The residue was treated with 3 N. aqueous solution of hydrochloric acid and then selecively the addition of an aqueous ammonia solution. The aqueous mixture was evaporated to dryness and the resulting residue was purified by column chromatography through silica gel with whom taught 0,37 g specified in the connection header, melting at 122-125oC.

Getting 51. 5-{4-(3-Methylimidazo[5,4-d]pyrimidine-2 - ylethoxy)benzyl} -3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that the used of 0.37 g of 2-hydroxymethyl-3-methylimidazo[5,4-d] pyrimidine (obtained as described in obtaining 50), of 2.51 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, of 1.34 ml tributylphosphine, 1,36, 1,1'-(azodicarbon)piperidine and 50 ml of benzene, and as a result have learnt specified in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in the ratio 2:1 by volume) and then from 1:1 to 1:2 by volume, and then a mixture of ethyl acetate and ethanol in the ratio 6: 1 by volume. The desired fractions were collected and concentrated by evaporation under reduced pressure. Concentrate more was purified by preparative reversed-phase high-speed liquid chromatography through UMS-Pack ODS-A (product F. "UMS Inc.) using as eluent a mixture of acetonitrile, water, acetic acid and triethylamine in about>C (softening).

Getting 52. 2-(4-Chlorobenzyl)amino-3-nitropyridine.

A mixture of 10.3 g of 2-hydroxy-3-nitropyridine and 25.5 ml thionyl chloride was heated under reflux for 2.5 h, after which the mixture was quickly added to 1.1 ml of dimethylformamide and heated it under reflux for 2.5 hours, after this time the reaction mixture was freed from solvent by evaporation under reduced pressure. To the resulting residue was added 80 ml of toluene and 19.1 g of sodium carbonate, and then to the mixture was added dropwise a solution of 12.3 ml of 4-chlorobenzylamino in 20 ml of toluene, and the resulting mixture was stirred at 85oC for 4 h, after this time the reaction mixture was removed by filtration of insoluble materials. The filtrate was washed with water and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The obtained residue was led by rubbing with 2-propanol, resulting in 12.0 g specified in the title compound, melting at 95-96oC.

Getting 53. 3-Amino-2-(4-chlorbenzyl)aminopyridine.

Repeating a similar procedure to that described in obtaining 42, except hydrate of tin chloride (II), 0.36 g of sodium borohydride and 150 ml of a mixture (9:1 by volume) of ethyl acetate and 2-methyl-2 propanol, and the result was indicated in the title compound as crude product. This crude product was led by rubbing with a mixture of ethyl acetate and hexane, resulting in 3,55 g specified in the title compound, melting at 123-125oC.

Getting 54. 2-Hydroxymethyl-3-(4-phenylbenzyl)imidazo[5,4-b]pyridine.

To a suspension of 1.1 g of sodium hydride (as a 55% by weight dispersion in mineral oil, and pre-washed with hexane) in 100 ml of dimethylformamide was added 3,74 g of 2-hydroxymethyl-3H-imidazo[5,4-b]pyridine, and the resulting mixture was stirred at room temperature for 2 hours thereafter, to the mixture was added dropwise (under ice cooling)solution 5,07 g of 4-(chloromethyl)diphenyl in 20 ml of dimethylformamide, and the resulting mixture was stirred at room temperature for 2 hours Then gave it to stand overnight. Then the reaction mixture was freed from dimethylformamide by distillation under reduced pressure. The obtained residue was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:3 by volume, which gave the 4-{3-(4-Phenylbenzyl)imidazo[5,4-b]pyridine-2 - ylethoxy} -benzyl]-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 0.5 g of 2-hydroxymethyl-3-(4-phenylbenzyl)imidazo[5,4-b] pyridine (obtained as described in obtaining 54), 0,738 g of 5-(4-hydroxybenzyl)-3 - triphenyltetrazolium-2,4-dione, of 0.43 ml tributylphosphine, 0.4 g of 1,1'-(azodicarbon)piperidine and 20 ml of benzene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient chromatography using as eluent mixtures of hexane and ethyl acetate in the ratio of from 1:2 to 1:3 by volume, which gave 0.95 g specified in the header of the compounds having Rf= 0,44 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio of 1:3 by volume).

Getting 56. 2-Amino-5-bromo-3-nitropyridine.

To 25,0 g 2-amino-5-bromopyridine was added 100 ml of concentrated sulfuric acid, and then to the mixture was added dropwise at 50-60oC for 1 h, 8,9 ml of concentrated nitric acid. Upon expiration of the specified time the specified mixture was poured into ice water and neutral is tion and washed with ethanol, receiving a result of 19.1 g specified in the title compound, melting at 180-182oC.

Getting 57. 5-Bromo-2,3-diaminopyridine.

Repeating a similar procedure to that described in obtaining 42, except that he used to 12.0 g of 2-amino-5-bromo-3-nitropyridine (obtained as described in obtaining 56), to 62.1 g of dihydrate of tin chloride (II), 1.04 g of sodium borohydride and 300 ml of a mixture (9:1 by volume) of ethyl acetate and 2-methyl-2-propanol, and the result was indicated in the title compound as crude product. This crude product was led by rubbing with a mixture of ethyl acetate and hexane, which resulted in 7,46 g specified in the title compound, melting at 135-137oC.

Getting 58. 6-Bromo-2-hydroxymethyl-3H-imidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 43, except that he used to 7.00 g of 5-bromo-2,3-diaminopyridine (obtained as described in obtaining 57) and 8.50 g of glycolic acid, and the result has been specified in the header of the crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of etelaat the P>oC.

Getting 59. 6-Bromo-2-hydroxymethyl-3-methylimidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 15, except that the reaction was carried out using 3.00 g of 6-bromo-2-hydroxymethyl-3H-imidazo[5,4-b] pyridine (obtained as described in obtaining 58), of 0.58 g of sodium hydride (as a 55% by weight dispersion in mineral oil) of 0.92 ml under the conditions and 60 ml of dimethylformamide. After the reaction with methyliodide the reaction mixture was freed from dimethylformamide by distillation under reduced pressure. The residue was diluted with water, then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The obtained residue was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and ethanol in the ratio of 50:1 by volume, which resulted in 1.40 g specified in the title compound, melting at 142-144oC.

Getting 60. 5-{4-(6-Bromo-3-methylimidazo[5,4 - b]pyridine-2-ylethoxy)-benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeated the procedure similar to t is-b] pyridine (obtained, as described in obtaining 59), 2,60 g of 5-(4-hydroxybenzyl)-3 - triphenyltetrazolium-2,4-dione, 1.39 ml tributylphosphine, 1,41 g of 1,1'-(azodicarbon)dipiperidino and 35 ml of toluene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume, which resulted in 3,43 g specified in the title compound, melting at 97-100oC (softening).

Getting 61. 2-Amino-5-chloro-3-nitropyridine.

Repeating a similar procedure to that described in obtaining 56, except that he used to 25.0 g of 2-amino-5-chloropyridine, 100 ml of concentrated sulfuric acid and 12.5 ml of concentrated nitric acid, and as a result got 18,5 g specified in the title compound, melting at 138-139oC.

Getting 62. 5-Chloro-2,3-diaminopyridine.

Repeating a similar procedure to that described in obtaining 42, except that used 12.5 g of 2-amino-5-chloro-3-nitropyridine (obtained as described in obtaining 61), 82,0 g of dihydrate of tin chloride (II), 1.35 g of sodium borohydride and 300 ml of SV as the crude product. This crude product was led by rubbing with a mixture of ethyl acetate and hexane, resulting in 8,14 g specified in the title compound, melting at 164-165oC.

Getting 63. 6-Chloro-2-hydroxymethyl-3H-imidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 43, except toga that used to 7.67 g of 5-Chloro-2,3 - diaminopyridine (obtained as described in obtaining 62) and 18.6 g of glycolic acid, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the ratio of 10:1 by volume, which resulted in 8,33 g specified in the title compound, melting at 209-211oC.

Getting 64. 6-Chloro-2-hydroxymethyl-3-methylimidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 59, except that used 3.00 g of 6-chloro-2-hydroxymethyl - 3H-imidazo[5,4-b] pyridine (obtained as described in obtaining 63), 0.71 g of sodium hydride (as a 55% by weight dispersion in mineral oil) of 1.03 ml under the conditions and 50 ml timecompany product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of ethyl acetate and methanol in the ratio of from 1:0 to 50:1 by volume, that resulted in 0.87 g specified in the title compound, melting at 141-142oC.

Getting 65. 5-{ 4-(6-Chloro-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)- benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 0.52 g of 6-chloro-2-hydroxymethyl-3-methylimidazo[5,4-b] pyridine (obtained as described in obtaining 64), of 1.23 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, of 0.66 ml tributylphosphine, of 0.67 g of 1,1'-(azodicarbon)piperidine and 20 ml of toluene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume) and obtained 1.51 g specified in the title compound, melting at 82-84oC (softening).

Getting 66. 6-Chloro-2-methylamino-3-nitropyridine.

To a mixture of 29.0 g of 2,6-dichloro-3-nitropyridine, 300 ml of ethanol and 36.6 g of sodium carbonate was added dropwise (ice cooling) to 20.0 ml of 30% ethanol solution of methylamine, and the mixture was stirred at room temperature tadili water, then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was led by rubbing with ethanol, resulting in 22,3 g specified in the title compound, melting at 114oC.

Getting 67. 6-Methoxy-2-methylamino-3-nitropyridine.

To a solution of 6.00 g of 6-chloro-2-methylamino-3-nitropyridine (obtained as described in getting 66) in 120 ml of methanol at room temperature was added dropwise 19 ml of a 28% methanol solution of sodium methoxide, and the resulting mixture was stirred at room temperature for 3 hours, after this time the reaction mixture was poured into water, then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was led by rubbing with ethanol, which resulted in 5.34 g specified in the title compound, melting at 152-153oC.

Getting 68. 3-Amino-6-methoxy-2-methylaminopropane.

Repeated the procedure similar to (received, as described in getting 67), 0,70 g 10% (m/m) of palladium on coal and 50 ml of dioxane, and the result was 2.66 g specified in the header of the compounds having Rf= 0,12 (thin-layer chromatography on silica gel using as developing solvent a mixture (1:1 by volume) hexane and ethyl acetate).

Getting 69. 2-Hydroxymethyl-5-methoxy-3-methylimidazo[5,4-b]pyridine.

A solution of 2.20 g of 3-amino-6-methoxy-2-methylaminopropane (obtained as described in getting 68) and 3.30 g of glycolic acid in 40 ml of toluene was heated under reflux for 4 hours after this time the reaction mixture was poured into water, then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the ratio of 30:1 by volume and as a result got 620g specified in the title compound, melting at 138-140oC.

Getting 70. 5-{4-(5-Methoxy-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl}-3-triphenyltetrazolium-the objects of study were 0.25 g of 2-hydroxymethyl-5-methoxy-3-methylimidazo[5,4-b] pyridine (obtained, as described in getting 69), 0.66 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 0,35 ml tributylphosphine, 0.36 g of 1,1'-(azodicarbon)piperidine and 15 ml of toluene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume, resulting in 0,70 g specified in the title compound, melting at 80-85oC (softening).

Getting 71. 2-tert-Butyldimethylsilyloxy-1H-imidazo[4,5-c]-pyridine.

Repeating a similar procedure to that described in obtaining 49, except that he used to 5.00 g of 2-hydroxymethyl-1H - imidazo[4,5-c] pyridine, 6.85 g of imidazole, 7,58 g of tert-butyldimethylsilyloxy and 100 ml of dimethylformamide, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the ratio of 10:1 by volume) and got 7,40 g specified in the title compound, melting at 53-55oC.

Poluchennuyu the as described in obtaining 59, except that he used to 7.4 g of 2-tert-butyldimethylsilyloxy-1H-imidazo[5,4-C] pyridine (obtained as described in getting 71), of 1.23 g of sodium hydride (as a 55% by weight dispersion in mineral oil), 2.0 ml under the conditions and 200 ml of dimethylformamide, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the ratio of 10: 1 by volume) and got 3,30 g specified in the title compound, melting at 93-95oC.

Getting 73. 2-Hydroxymethyl-1-methylimidazo[4,5-c]pyridine.

A solution of 3.00 g of 2-tert-butyldimethylsilyloxy-1 methylimidazo [4,5-c] pyridine (obtained as described in getting 72) in 60 ml of a mixture (1:1:1 by volume) tetrahydrofuran, acetic acid and water was stirred at room temperature for 1 h and then at 60oC for 5 hours, after this time the reaction mixture was freed from solvent by distillation. The obtained residue was mixed with aqueous solution of sodium bicarbonate and then concentrated by evaporation under reduced the acetate and methanol in the ratio of 10:1 by volume, receiving a result of 1.97 g specified in the title compound, melting at 285-290oC.

Getting 74. 5-{4-(1-Methylimidazo[4,5-c]pyridine-2 - ylethoxy)benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used was 1.94 g of 2-hydroxymethyl-1-methylimidazo[4,5-c] pyridine (obtained as described in getting 73), 5,71 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, 3,1 ml tributylphosphine, to 3.09 g of 1,1'-(azodicarbon)piperidine and 50 ml of toluene, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of methyl acetate and methanol in the ratio of from 1:0 to 10:1 by volume and as a result got 3,55 g specified in the header of the compounds having Rf= 0,08 (thin-layer chromatography on silica gel using ethyl acetate as the developing solvent).

Obtaining 75. 2-Chloro-3-formylpyridine.

To a solution of 16.7 g of 2-chloro-3-lepirudin in 200 ml of tetrahydrofuran was added 200 ml of 1.02 M hexane rasnow the mixture was stirred at room temperature for 1 h After this time the reaction mixture was added at 0oC hydrochloric acid, and then the mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium carbonate and saturated aqueous sodium chloride (in that order), then was dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in the ratio of from 6: 1 to 5:1 by volume, resulting in 7.0 g specified in the header of the compounds having Rf= 0,50 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio 2:1 by volume).

Getting 76. Ethyl-2-azido-3-(2-chloropyridin-3-yl)-3-hydroxypropionate.

A mixture of 2.0 g of 2-chloro-3-formylpyridine (obtained as described in obtaining 75), 7.5 g of ethylacetoacetate and 87 ml of 65 mm ethanol solution ethoxide sodium was stirred at 0oC for 2 h then the reaction mixture was poured into water and then extracted with ethyl acetate. Extrazonal order) and was dried over anhydrous sodium sulfate, then solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 3:1 by volume and as a result got 2.83 g specified in the header of the compounds having Rf= 0,61 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio 2:1 by volume).

Getting 77. Ethyl-2-azido-3-tert-butyldimethylsilyloxy-3- (2-chloropyridin-3-yl)propionate.

Repeating a similar procedure to that described in obtaining 49, except that used 3,90 g ethyl-2-azido-3-(2-chloropyridin-3-yl)-3-hydroxypropionate (obtained as described in getting 76), 8.6 g of tert-butyldimethylsilyloxy, 10 g of imidazole and 80 ml of dimethylformamide, and the result was indicated in the title compound as crude product. This crude product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 8:1 by volume, which gave 5.6 g specified in the header of the compounds having Rf= 0,31 (thin-ATA in the ratio of 3:1 by volume).

Getting 78. Ethyl-2-amino-3-tert-butyldimethylsilyloxy-3- (2-chloropyridin-3-yl)propionate.

A mixture of 5.6 g of ethyl-2-azido-3-tert-butyldimethylsilyloxy-3- (2-chloropyridin-3-yl)propionate (obtained as described in getting 77), 7.5 g of triphenylphosphine and 18 ml of a mixture (8:1 by volume) of tetrahydrofuran and water was stirred at room temperature for 3 hours after this time the reaction mixture was freed from solvent by distillation. The residue was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 5:1 by volume, and then a mixture of methylene chloride and methanol in the ratio of 50:1 by volume, which resulted in 5.9 g specified in the header of the compounds having Rf= 0,59 (thin-layer chromatography on silica gel using as developing solvent a mixture of methylene chloride and methanol in the ratio of 15:1 by volume).

Getting 79. Ethyl-3-tert-butyldimethylsilyloxy-3-(2-chloropyridin - 3-yl)-2-methylaminopropane.

To a solution of 0.7 g of ethyl-2-amino-3-tert-butyldimethylsilyloxy-3-(2 - chloropyridin-3-yl)propionate (obtained as described in getting 78) in 4 ml of a mixture (3: 2 by volume) methylene chloride and water at 0ooC within 15 minutes after this time the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, and then was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in the ratio of from 8:1 to 1:1 by volume) and received in the 200 mg specified in the header of the compounds having Rf= 0,38 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio of 3:1 by volume).

80. Ethyl-1-methyl-7-azaindole-2-carboxylate.

The solution 994 mg ethyl-3-tert-butyldimethylsilyloxy-3-(2 - chloropyridin-3-yl)-2-methylaminopropane (obtained as described in getting 79) and 393 mg of 1,5-diazabicyclo[4.3.0]-non-5-ene in 5 ml of dimethylformamide was stirred at 150oC for 5 hours after this time the reaction mixture was poured into a saturated aqueous solution of ameriglide, then extragere, then solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in the ratio of from 9:1 to 5: 1 by volume) and received the 150 mg specified in the header of the compounds having Rf= 0,40 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio of 3:1 by volume).

Getting 81. 2-Hydroxymethyl-1-methyl-7-azaindole.

Repeating a similar procedure to that described in the getting 2, except that used 130 mg of ethyl-1-methyl-7-azaindole-2 - carboxylate (obtained as described in obtaining 80), 23 mg of sociallyengaged and 2 ml of tetrahydrofuran, and the obtained 110 mg specified in the header of the compounds having Rf= 0,47 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio of 3:1 by volume).

Getting 82. 5-[4-(1-Methyl-7-azaindole-2-ylethoxy)benzyl] -3-triphenyl-methylthiazolidine-2,4-dione.

A solution of 103 mg of 2-hydroxyazetidine-2,4-dione, 166 mg of diethylazodicarboxylate and 250 mg of triphenylphosphine in 3 ml of tetrahydrofuran was stirred at room temperature for 15 hours, after this time the reaction mixture was freed from solvent by distillation. The obtained residue was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in the ratio of from 5:1 to 4:1 by volume and as a result received 277 mg specified in the header of the compounds having Rf= 0,41 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume).

Getting 83. 3-Nitro-2-phenylaminopyrimidine.

Repeating a similar procedure to that described in getting 66, except that in the reaction used 15 g of 2-chloro-3-nitropyridine, 13,22 g of aniline and 20,07 g of sodium carbonate in 180 ml of toluene. After processing the product as described in getting 66, the crude product was purified by column chromatography through silica gel, using a mixture of ethyl acetate and hexane in a ratio of 1:5 by volume, and as a result got to 6.9 g specified in the connection header, the melt is similar to that as described in example 6, except that carried out the hydrogenation of 6.9 g of 3-nitro-2-phenylaminopyrimidine (obtained as described in getting 83) in a mixture of 150 ml of ethanol and 50 ml of dioxane in the presence of 1.38 g of 10% (m/m) of palladium on coal. After processing the product as described in example 6, received 4,2 g specified in the title compound, melting at 137-140oC.

Getting 85. 2-Hydroxymethyl-5,7-dimethyl-3H-imidazo[5,4-b]pyridine.

The mixture 13,72 g of 2,3-diamino-4,6-dimethylpyridine and 25 g of glycolic acid in 200 ml of toluene was heated under reflux for 3.5 h with azeotropic distillation of the water formed during the reaction. With the expiration of this time the reaction mixture was freed from toluene by decantation, and the oily residue was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of ethanol and ethyl acetate in the ratio from 2:3 to 1:1 by volume, which resulted in 2.7 g specified in the title compound, melting at 244-246oC.

Getting 86. 2-Hydroxymethyl-3,5,7-trimethylimidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 15, except poluchenii 85), 0.64 g of sodium hydride (as a 55% by weight dispersion in mineral oil, 2.2 g of iodomethane and 80 ml of dimethylformamide. After processing the product as described in obtaining 15, the crude product was purified by column chromatography through silica gel, using as eluent a mixture of ethanol and ethyl acetate in the ratio of 1:6 by volume, followed by recrystallization from ethyl acetate and resulted in 1.5 g specified in the title compound, melting at 178-179oC.

Getting 87. 5-{4-(3,5,7-Trimethylimidazo[5,4-b]pyridine-2-ylethoxy)-benzyl}- 3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 1.47 g of 2-hydroxymethyl-3,5,7-trimethylimidazo[5,4-b] pyridine (obtained as described in getting 86), 3.58 g of 5-(4-hydroxybenzyl)-3 - triphenyltetrazolium-2,4-dione, 1,87 g tributylphosphine, 2,33 g of 1,1'-(azodicarbon)piperidine and 50 ml of toluene. After processing the product as described in obtaining 4, the crude product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume and as a result receive the 2-Methylamino-3-nitro-6-phenylthiourea.

To a suspension of 1.54 g of sodium hydride (as a 55% by weight dispersion in mineral oil, and pre-washed with hexane) in 30 ml of dimethylformamide was added dropwise 3.6 ml of thiophenol, and the resulting mixture was stirred at room temperature for 1 h Then the mixture was added dropwise to a solution of 6.00 6-chloro-2-methylamino-3-nitropyridine (obtained as described in getting 66) in dimethylformamide (ice cooling), and the resulting mixture was stirred at 5oC for 2 h With the expiration of this time the reaction mixture was freed from dimethylformamide by distillation under reduced pressure. The residue was mixed with water, and the aqueous mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 3:1 by volume) and received as a result of 8.40 g specified in the header of the compounds having Rf= 0,67 (thin-layer chromatography on silica gel using as developing solvent a mixture of hexane">

Repeating a similar procedure to that described in example 6, except that carried out the hydrogenation of 5.40 g of 2-methylamino-3-nitro-6-phenylthiophene (obtained as described in getting 88) in 80 ml of methanol in the presence of 1,10 g 10% (m/m) of palladium on coal. After processing the product as described in example 6, received 4,00 g specified in the header of the compounds having Rf= 0,69 (thin-layer chromatography on silica gel using as a developing solvent ethyl acetate).

Getting to 90. 2-Hydroxymethyl-3-methyl-5-phenylthioureido[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 43, except that used 2,62 g 3-amino-2-methylamine-6-phenylthiophene (obtained as described in getting 89) and 2.58 g of glycolic acid and the product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of ethyl acetate and methanol in the ratio of from 50:1 to 10:1 by volume, which gave 1,80 g specified in the title compound, melting at 119-120oC.

Getting 91. 5-{4-(3-Methyl-5-phenylthioureido[5,4-b]pyridine - 2-yl-methoxy)benzyl}-3-triphenylmethane is used to 0.70 g of 2-hydroxymethyl-3-methyl-5-phenylthioureido[5,4-b] pyridine (obtained, as described in obtaining 90), 1.20 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, of 0.64 ml tributylphosphine, 0.65 g of 1,1'-(azodicarbon)dipiperidino and 25 ml of toluene and the product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume, resulting in a received 1,61 g specified in the title compound, melting at 90-95oC (softening).

Getting 92. 6-Benzyloxy-2-methylamino-3-nitropyridine.

Repeating a similar procedure to that described in getting 88, except that he used to 7.00 g of 6-chloro-2-methylamino-3-nitropyridine (obtained as described in getting 66), 1,79 g of sodium hydride (as a 55% by weight dispersion in mineral oil) in 4.3 ml of benzyl alcohol and 150 ml of dimethylformamide. After processing the product as described in getting 88, the crude product was led by rubbing with isopropanol, which gave 9,02 g specified in the title compound, melting at 149oC.

Getting 93. 3-Amino-6-benzyloxy-2-methylaminopropane.

To a solution of 8.50 g of 6-benzyloxy-2-methylamino-3-nitropyridine (obtained as described in getting 92)eat was stirred at room temperature for one hour. After the reaction mixture was filtered to remove insoluble material. The filtrate was freed from solvent by distillation under reduced pressure, and the obtained residue was dissolved in ethyl acetate. The solution was washed with an aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride (in that order). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure, resulting in 7.50 g specified in the header of the compounds having Rf= 0,63 (thin-layer chromatography on silica gel using ethyl acetate as the developing solvent).

Getting 94. 5-Benzyloxy-2-hydroxymethyl-3-methylimidazo- [5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 43, except that the reaction was carried out with the use of 7.50 g of 3-amino-6-benzyloxy-2-methylaminopropane (obtained as described in getting 93) and 7,46 g of glycolic acid. After processing the product as described in obtaining 43, the crude product was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the CSOs in the title compound, melting at 133-135oC.

Getting 95. 5-{ 4-(5-Benzyloxy-3-methyl-imidazo[5,4-b]pyridine - 2-ylethoxy)benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 3,15 g of 5-benzyloxy-2-hydroxymethyl-3-methylimidazo[5,4-b] pyridine (obtained as described in getting 94), 5.50 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, only 2.91 ml tributylphosphine, 2,95 g of 1,1'-(azodicarbon)dipiperidino and 100 ml of toluene and the product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of hexane and ethyl acetate in the ratio from 1:1 to 1:2 by volume, and as a result got 7,10 g specified in the title compound, melting at 88-90oC (softening).

Getting 96. 6 Ethoxy-2-methylamino-3-nitropyridine.

Repeating a similar procedure to that described in getting 88, except that he used to 6.00 g of 6-chloro-2-methylamino-3-nitropyridine (obtained as described in getting 66), 1.54 g of sodium hydride (as a 55% by weight dispersion in mineral oil), and 2.1 ml of ethanol and 150 ml of dimethylformamide. After processing PR is, receiving 5.10 g specified in the title compound, melting at 101oC.

Getting 97. 3-Amino-6-ethoxy-2-methylaminopropane.

Repeating a similar procedure to that described in example 6, except that carried out the hydrogenation of 4.95 g of 6-ethoxy-2-methylamino-3-nitropyridine (obtained as described in getting 96) in 100 ml of 1,4-dioxane in the presence of 1.00 10% (m/m) of palladium on coal. After processing the product as described in example 6, received 4,20 g specified in the header of the compounds having Rf= 0,57 (thin-layer chromatography on silica gel using ethyl acetate as the developing solvent).

Getting 98. 5-Ethoxy-2-hydroxymethyl-3-methylimidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 43, except that used 4.15 g of 3-amino-6-ethoxy-2-methylaminopropane (obtained as described in getting 97) and to 5.66 g of glycolic acid and the product was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the ratio of 10:1 by volume, resulting in a received 3,20 g specified in the title compound, melting ylmethyl-thiazolidin-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that he used to 1.00 g of 5-ethoxy-2-hydroxymethyl-3-methylimidazo[5,4-b] pyridine (obtained as described in getting 98), 2.25 g of 5-(4-hydroxybenzyl)-3 - triphenyltetrazolium-2,4-dione, 1,2 ml tributylphosphine, 1.22 g of 1,1'-(azodicarbon)dipiperidino and 60 ml of toluene, and the obtained product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1: 1, resulting in a received 2,81 g specified in the title compound, melting at 88-100oC (softening).

100. 6 Isopropoxy-2-methylamino-3-nitropyridine.

Repeating a similar procedure to that described in getting 88, except that he used to 6.00 g of 6-chloro-2-methylamino-3-nitropyridine (obtained as described in getting 66), 1.54 g of sodium hydride (as a 55% by weight dispersion in mineral oil), and 2.7 ml of isopropanol and 150 ml of dimethylformamide. After processing the product as described in getting 88, the crude product was led by rubbing with isopropanol, resulting in 6,10 g specified in the title compound, melting prgra, similar to that described in example 6, except that carried out the hydrogenation of 2.38 g of 6-isopropoxy-2-methylamino-3-nitropyridine (obtained as described in obtaining 100) in 50 ml of methanol in the presence of 0.50 g of 10% (m/m) of palladium on coal. After processing the product as described in example 6, was obtained from 2.00 g specified in the header of the compounds having Rf= 0,62 (thin-layer chromatography on silica gel using ethyl acetate as the developing solvent).

Getting 102. 5-Isopropoxy-2-hydroxymethyl-3-methylimidazo-[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 43, except that used 1,90 g 3-amino-6-isopropoxy-2-methylaminopropane (obtained as described in getting 101) and 2,39 g of glycolic acid and the resulting product was purified by column chromatography through silica gel, using as eluent a mixture of ethyl acetate and methanol in the ratio of 10:1 by volume, which resulted in 0,58 g specified in the title compound, melting at 125-127oC.

Getting 103. 5-{4-(5-Isopropoxy-3-methylimidazo[5,4-b]pyridine - 2-yl-methoxy)benzyl}-3-triphenyltetrazolium-2,4-dione.

P is propoxy-2-hydroxymethyl-3-methylimidazo[4,5-b] pyridine (obtained, as described in getting 102), to 0.69 g of 5-(4-hydroxybenzyl)-3-triphenyltetrazolium-2,4-dione, and 0.37 ml of tributylphosphine, 0,38 g of 1,1'-(azodicarbon)piperidine and 20 ml of toluene, and the obtained product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume, resulting in a received 0,85 g specified in the title compound, melting at 90-100oC (softening).

Getting 104. 2-Methylamino-3-nitropyridine.

Repeating a similar procedure to that described in getting 66, except that reaction was carried out 24,9 g of 2-chloro-3-nitropyridine, 41.7 sodium carbonate, an increase of 22.7 ml of 30% ethanol solution of methylamine in 250 ml of toluene. After processing the product as described in getting 66, the crude product was led by isopropanol, receiving 24,0 g specified in the title compound, melting at 52-53oC.

Getting 105. 3-Amino-2-methylaminopropane.

Repeating a similar procedure to that described in example 6, except that carried out the hydrogenation of 5.00 g of 2-methylamino-3-nitropyridine (obtained as described in getting 104) in 80 ml of 1,4-di g specified in the connection header, melting at 90-92oC.

Getting 106. 5-{4-[2-(1,3-dioxolane-2-yl)ethoxy]benzyl} thiazolidine-2,4-dione.

Repeating a similar procedure to that described in obtaining 46, except that used 15.0 g of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione, 8,80 g of sodium hydride (as a 55% by weight dispersion in mineral oil), 17 ml of 2-(2-bromacil)-1,3-dioxolane and 80 ml of dimethylformamide and the resulting product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume, the result has been to 6.67 g specified in the title compound, melting at 102-104oC.

Getting 107. 5-[4-(3-Oxopropoxy)benzyl]thiazolidin-2,4-dione.

The solution 6,30 g 5-{4-[2-(1,3-dioxolane-2-yl)ethoxy]benzyl}- thiazolidine-2,4-dione (obtained as described in getting 106) in a mixture (4:1 by volume) of acetic acid and water was stirred at 60oC for 6 hours At the end of this time the reaction mixture was freed from solvent by distillation under reduced pressure. The obtained residue was purified by column chromatography through silica gel, using as eluent a mixture of hexane and S="ptx2">

Getting 108. 2-Methylamino-3-nitro-6-phenylpyridine.

To a solution of 5.0 g of 6-chloro-2-methylamino-3-nitropyridine (obtained as described in getting 66) and 3.9 g of phenylboric in 80 ml of a mixture (1:1, by volume) of ethanol and toluene was added 50 ml of 2 N. of an aqueous solution of sodium carbonate and 0.34 g of 20% (m/m) of palladium hydroxide on charcoal, and the resulting mixture was stirred at 105oC for 4.5 hours At the end of this time the reaction mixture was filtered to remove palladium hydroxide on coal. The filtrate was concentrated by evaporation under reduced pressure, and the concentrate was diluted with water, then was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate, and then solvent was removed by distillation under reduced pressure. The residue was led by rubbing with ethanol, resulting in 4,75 g specified in the title compound, melting at 98-99oC.

Getting 109. 3-Amino-2-methylamino-6-phenylpyridine.

Repeating a similar procedure to that described in example 6, except that carried out the hydrogenation of 5.7 g of 2-methylamino-3 - nitro-6-phenylpyridine (obtained as described in getting 108) in 200 ml of a mixture (1: 1 by volume) ethanol and 1, 6, got 4.9g specified in the header of the compounds having Rf= 0,08 (thin-layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane in a ratio of 1:5 by volume).

Obtaining 110. 2-Hydroxymethyl-3-methyl-5-phenylimidazo[5,4-b]pyridine.

Repeating a similar procedure to that described in obtaining 43, except that he used to 4.9 g of 3-amino-2-methylamino-6-phenylpyridine (obtained as described in getting 109) and 5.6 g of glycolic acid and the resulting product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of ethyl acetate and ethanol in the ratio of from 1:0 to 10:1 by volume, resulting in a 0.9 g specified in the title compound, melting at 174-177oC.

Getting 111. 5-{ 4-(3-Methyl-5-phenylimidazo[5,4-b]pyridine-2 - ylethoxy)-benzyl}-3-triphenyltetrazolium-2,4-dione.

Repeating a similar procedure to that described in the getting 4, except that used 0.5 g of 2-hydroxymethyl-3-methyl-5 - phenylimidazo[5,4-b]pyridine (obtained as described in getting 110), 0.97 g of 5-(4-hydroxybenzyl)-3-triphenylamine product, as described in the getting 4, the crude product was purified by column chromatography through silica gel, using as eluent a mixture of hexane and ethyl acetate in the ratio of 1:1 by volume, resulting in 0.9 g specified in the header of the compounds having Rf= 0,26 (thin-layer chromatography on silica gel using as developing solvent a mixture of ethyl acetate and hexane in a ratio of 1:1 by volume).

Getting 112. 2-(4-Formylphenoxy)-3-methylimidazo[5.4 - b]pyridine.

Repeating a similar procedure to that described in the getting 4, except that used 500 mg 3 methylimidazo[5,4-b]]pyridine-2-ylmethanol (obtained as described in obtaining 15), 374 mg of 4-hydroxybenzaldehyde, 0,76 ml tributylphosphine, 773 mg of 1,1'-(azodicarbon)dipiperidino and 12 ml of toluene and the obtained product was purified by column chromatography through silica gel by the method of gradient elution using as eluent mixtures of ethyl acetate and methanol in the ratio of from 1:0 to 50:1 volume, resulting in a received 0,37 g specified in the title compound, melting at 124-125oC.

Recipe 1. The capsule.

Carefully move the

Magnesium stearate - 2

Total - 180

The mixture was then filtered through a sieve (60 mesh., the standard of Tilera). A mixture of 180 mg, weighed and distributed into gelatine capsules No. 3.

Recipe 2. Tablets.

The following ingredients are thoroughly mixed, mg:

Connection example 2 - 10

Lactose - 85

Corn starch - 34

Microcrystalline cellulose - 20

Magnesium stearate - 1

Total - 150

The mixture was compressed into tablets each weighing 150 mg If desired, tablets may be coated with sugar or other suitable coating.

Recipe 3. Granules.

The following ingredients are thoroughly mixed, mg:

Connection example 2 - 10

Lactose - 839

Corn starch - 150

Hydroxypropylcellulose - 1

Total - 1000

The mixture is then moistened with purified water, granularit in the granulator and dried to obtain granules.

1. Derivatives of thiazolidinedione General formula I

< / BR>
where X - indolyl, indolinyl, isoindolyl, isoindolines, imidazopyridine or imidazopyrimidines, unsubstituted or substituted by at least one Deputy, selected from alkyl groups, C1- C4, phenyl groups, triptoreline groups, akinaga a chlorine atom, the phenyl or trifluoromethyl;

Y is an oxygen atom or a sulfur atom;

The Z group of formula i or ii

< / BR>
< / BR>
R is hydrogen or C1- C4-alkyl;

m is an integer from 1 to 5,

or their pharmaceutically acceptable salts.

2. Connection on p. 1, where X is indayla, indolenine, asiandaily, imidazopyridine or imidazopyrimidines group, unsubstituted or substituted by 1 to 3 substituents defined in paragraph 1.

3. Connection on p. 1, where X is indayla, indolenine, imidazopyridine or imidazopyridine group, unsubstituted or substituted by 1 to 3 substituents defined in paragraph 1.

4. Connection on p. 1, where X is indayla, indolinyl or imidazopyridine group, unsubstituted or substituted by 1 to 3 substituents defined in paragraph 1.

5. Connection on p. 1, where X is indolenine or imidazopyridine group, unsubstituted or substituted by 1 to 3 substituents selected from the group comprising C1- C4is an alkyl group, a C1- C4-alkoxygroup, benzyloxy, halogen atom, phenylthiourea, C1- C4-allylthiourea, triptorelin group and phenyl group.

6. Connection on p. 1, where X is imidazopyridine, ethyl group, a methoxy group, ethoxypropan, isopropoxy, benzyloxy, a chlorine atom, phenylthiourea and phenyl group.

7. Connection PP.1 - 6, where R is a hydrogen atom.

8. Connection PP.1 to 7, where Z is 2,4-dioxothiazolidine-5-ylmethyl.

9. Connection on p. 1, where X is indolinyl or imidazopyridine, unsubstituted or substituted by 1 to 3 substituents selected from C1- C4-alkyl, C1- C4-alkoxy, benzyloxy, halogen atoms, phenylthio, C1- C4-alkylthio, trifloromethyl and phenyl, Y is an oxygen atom, Z - 2,4-dioxothiazolidine-5-ylmethyl, R is hydrogen and m is an integer 1 to 5.

10. Connection on p. 1, where X is imidazopyridine, unsubstituted or substituted by 1 to 3 substituents selected from methyl, ethyl, methoxy, ethoxy, isopropoxy, benzyloxy, chlorine atom, phenylthio and phenyl, Y is an oxygen atom, Z - 2,4-dioxothiazolidine-5-ylmethyl, R is hydrogen, m is an integer 1 to 5.

11. Connection on p. 1, representing 5-{4-(3-methylimidazo[5,4-b] pyridine-2-ylethoxy)benzyl}thiazolidine-2,4-dione.

12. Connection on p. 1, representing 5-{4-(5-chloro-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl}thiazolidine-2,4-dione.

13. Connection on p. 1, representing redstavlyaya a 5-{4-(5-hydroxy-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl}-thiazolidine-2,4-dione.

15. Connection on p. 1, representing 5-{4-(5-ethoxy-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl}-thiazolidine-2,4-dione.

16. Connection on p. 1, representing 5-{4-(5-isopropoxy-3-methylimidazo[5,4-b]pyridine-2-ylethoxy)benzyl}-thiazolidine-2,4-dione.

17. Pharmaceutical composition having hypoglycemic and inhibitory alsoreported activity, containing as active agent an effective amount of a derivative thiazolidinedione in a mixture with a pharmaceutically acceptable carrier or diluent, wherein as derived thiazolidinedione contains a compound of formula I or its pharmaceutically acceptable salt according to any one of paragraphs.1 - 16.

18. The method of treatment or prophylaxis of diseases which can be treated with compounds with hypoglycemic and/or inhibitory alsoreported activity, comprising the administration to a mammal an effective amount of a derivative thiazolidinedione as active compounds, characterized in that is used as a derivative thiazolidinedione compound of formula I or its pharmaceutically acceptable salt according to any one of paragraphs.1 - 16.

 

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< / BR>
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