Aminoindazole derivatives as medications, method of their obtaining and pharmaceutical compositions containing them

FIELD: chemistry, pharmaceutics.

SUBSTANCE: claimed invention relates to application of indazole derivatives of general formula (I) , in which: R stands for O; R3 stands for radical (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, said radicals being unsubstituted or substituted with one or several substitutes, given in item 1 of the formula; R4, R5, R6 and R7, independently on each other are selected from following radicals; hydrogen atom, halogen, CN, NO2, NH2, NHSO2R9, trifluoromethyl, trifluoromethoxygroup, (C1-C6)-alkyl, phenyl, phenyl-(C1-C6)-alkyl, pyridyl, possibly substituted with amino or hydroxygroup, thienyl, furanyl, morpholino, phenyl being unsubstituted or substituted with one or several substitutes, given in item 1 of the formula; R8, R9, R10, R11, independently on each other, stand for hydrogen atom, (C1-C6)-alkyl, phenyl possibly substituted with halogen; their racemates, enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts for obtaining medication, inhibiting phosphorylation of Tau-protein. Invention also relates to novel compounds of formula (I), particular indazole derivatives, their racemates, enantiomers, tautomers and pharmaceutically acceptable salts, pharmaceutical composition and based on them medication which inhibits Tau-protein phosphorylation, as well as to method of obtaining compounds of formula (I).

EFFECT: obtaining medication based on indazole derivatives, inhibiting Tau-protein phosphorylation.

9 cl, 118 ex, 3 ex

 

The present invention relates to the use of derivatives aminoindazole formula (I):

or their pharmaceutically acceptable salts as a kinase inhibitor.

The objects of the invention are the use of derivatives aminoindazole formula (I) and their pharmaceutically acceptable salts for pharmaceutical compositions intended for the prevention and treatment of diseases that may occur due to abnormal activity of kinases such as, for example, actively involved in neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontoparietal dementia, corticobasal degeneration, diseases of the Peak, cerebrovascular disorders, cranial and spinal injuries and peripheral neuropathies, obesity, metabolic diseases, type II diabetes, essential hypertension, cardiovascular atherosclerotic diseases, polycystic ovary syndrome, syndrome X, immunodeficiency and cancer; pharmaceutical compositions containing the new derivatives aminoindazole and their pharmaceutically acceptable salts; and new derivatives of aminoindazole and their pharmaceutically acceptable salts.

The present invention relates to the derivatives of aminoindazole formula (I)in which:

R means O, S or NH;

R3 means adikal (C 1-C6)-alkyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl; aryl or heteroaryl condensed with (C1-C10-cycloalkyl; heterocyclic residue, cycloalkyl, substituted, politically, alkenyl, quinil, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R4, R5, R6 and R7, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, -O-SO2R8, -SO2-O-R8, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, quinil, substituted, politically, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHS 2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

with the exception of 3-(2-nitrobenzamide)indazole, 3-(2-aminobenzamide)indazole, 3-(4-chloro-2-nitrobenzamide)indazole, 3-(5-chloro-2-nitrobenzamide)indazole, 3-(2-amino-4-chlorobenzamido)-indazole, 3-(2-amino-5-chlorobenzamido)indazole, 3-(benzamido)-indazole, 3-(4-methylbenzamide)indazole, 3-(4-chlorobenzamido)-indazole, 3-(4-nitrobenzamide)indazole, 3-acetamidophenol, N-(1H-indazol-3-yl)butanamide, N-(1H-indazol-3-yl)phenylacetamide, N-(1H-indazol-3-yl)benzhydrylamine, 5-amino-3-acetamidophenol, 3-(2-hydroxybenzamide)indazole, N-(6-chloro-1H-indazol-3-yl)-2,2,2-trifurcated, N-(6-chloro-1H-indazol-3-yl)-2-furancarboxylic, N-(6-chloro-1H-indazol-3-yl)-2-thiophencarboxylic, N-(6-chloro-1H-indazol-3-yl)-4-(hexyl-oxy)benzamide, 3-chloro-N-(6-chloro-1H-indazol-3-yl)benzamide, 4-chloro-N-(6-chloro-1H-indazol-3-yl)benzamide, N-(5-nitro-1H-indazol-3-yl)ndimethylacetamide;

their isomers and the mixtures their racemates, the enantiomers, diastereoisomers, tautomers and their pharmaceutically acceptable salts.

In particular, the present invention relates to the derivatives of aminoindazole formula (I)in which:

R means O, S or NH;

R3 means a radical (C1-C6)-alkyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, cycloalkyl, alkenyl, quinil, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R4 and R7 means a hydrogen atom;

R5, R6, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, -O-SO2R8, -SO2-O-R8, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, cycloalkyl, heterocyclic residue, alkenyl, quinil, substituted, politically, and these radicals are unsubstituted or substituted one is m or more substituents, chosen among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

with the exception of 3-(2-nitrobenzamide)indazole, 3-(2-aminobenzamide)indazole, 3-(4-chloro-2-nitrobenzamide)indazole, 3-(5-chloro-2-nitrobenzamide)indazole, 3-(2-amino-4-chlorobenzamido)-indazole, 3-(2-amino-5-chlorobenzamido)indazole, 3-(benzamido)-indazole, 3-(4-methylbenzamide)indazole, 3-(4-chlorobenzamido)-indazole, 3-(4-nitrobenzamide)indazole, 3-acetamidophenol, N-(1H-indazol-3-yl)butanamide, N-(1H-indazol-3-yl)phenylacetamide, N-(1H-indazol-3-yl)benzhydrylamine, 5-amino-3-acetamidophenol, 3-(2-hydroxybenzamide)indazole, N-(6-chloro-1H-indazol-3-yl)-2,2,2-trifurcated, N-(6-chloro-1H-indazol-3-yl)-2-furancarboxylic, N-(6-chloro-1H-indazol-3-yl)-2-thiophencarboxylic, N-(6-chloro-1H-indazol-3-yl)-4-(hexyloxy)benzamide, 3-the ers-N-(6-chloro-1H-indazol-3-yl)benzamide, 4-chloro-N-(6-chloro-1H-indazol-3-yl)benzamide, N-(5-nitro-1H-indazol-3-yl)ndimethylacetamide;

their isomers, their mixtures, their racemates, the enantiomers, diastereoisomers, tautomers and their pharmaceutically acceptable salts.

And preferably the present invention relates to the derivatives of aminoindazole formula (I)in which:

R means O;

R4 and R7 denote H;

R3 means a radical (C1-C6)-alkyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R5 and R6, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, moreover, these radicals are unsubstituted or substituted by one or more substituents, chosen among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

with the exception of 3-(2-nitrobenzamide)indazole, 3-(2-aminobenzamide)indazole, 3-(4-chloro-2-nitrobenzamide)indazole, 3-(5-chloro-2-nitrobenzamide)indazole, 3-(2-amino-4-chlorobenzamido)-indazole, 3-(2-amino-5-chlorobenzamido)indazole, 3-(benzamido)-indazole, 3-(4-methylbenzamide)indazole, 3-(4-chlorobenzamido)-indazole, 3-(4-nitrobenzamide)indazole, 3-acetamidophenol, N-(1H-indazol-3-yl)butanamide, N-(1H-indazol-3-yl)phenylacetamide, N-(1H-indazol-3-yl)benzhydrylamine, 3-acetamidophenol, 5-amino-3-acetamidophenol, 3-(2-hydroxybenzamide)indazole, N-(6-chloro-1H-indazol-3-yl)-2,2,2-trifurcated, N-(6-chloro-1H-indazol-3-yl)-2-furancarboxylic, N-(6-chloro-1H-indazol-3-yl)-2-thiophencarboxylic, N-(6-chloro-1H-indazol-3-yl)-4-(Gex is lexi)benzamide, 3-chloro-N-(6-chloro-1H-indazol-3-yl)benzamide, 4-chloro-N-(6-chloro-1H-indazol-3-yl)benzamide, N-(5-nitro-1H-indazol-3-yl)ndimethylacetamide;

their racemates, the enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts.

The present invention relates to the use of derivatives aminoindazole General formula (I):

in which:

R means O, S or NH;

R3 means a radical (C1-C6)-alkyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl; aryl or heteroaryl condensed with (C1-C10-cycloalkyl; heterocyclic residue, cycloalkyl, substituted, politically, alkenyl, quinil, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R4, R5, R6 and R7, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, -O-SO2R8, -SO2-O-R8, trifluoromethyl, tripterocarpa, (C1 6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, quinil, substituted, politically, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

their isomers, their mixtures, their racemates, enantiomers, diastereoisomers, tautomers and their pharmaceutically acceptable salts for obtaining medicines.

In particular, the present invention relates to the use of derivatives aminoindazole formula (I)in which:

R means O, S or NH;

R3 means a radical (C1-C6)-alkyl, aryl, aryl-(C1-C6 )-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, cycloalkyl, alkenyl, quinil, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R4 and R7 means a hydrogen atom;

R5, R6, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, -O-SO2R8, -SO2-O-R8, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, cycloalkyl, heterocyclic residue, alkenyl, quinil, substituted, politically, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently from each other is a, means a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

their isomers, their mixtures, their racemates, enantiomers, diastereoisomers, tautomers and their pharmaceutically acceptable salts for obtaining medicines.

And preferably the present invention relates to the use of derivatives aminoindazole formula (I)in which:

R means O;

R4 and R7 denote H;

R3 means a radical (C1-C6)-alkyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R5 and R6, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH 2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

their racemates, enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts for obtaining medicines.

In the above and the following definitions (C1-C6)-alkyl radicals contain 1 to 6 carbon atoms in inani or branched chain; alkeneamine radicals contain 2 to 6 carbon atoms and 1-3 paired or no double bond in a linear or branched chain; alkyline radicals contain 2 to 6 carbon atoms and 1-3 paired or not triple bond in a linear or branched chain; aryl radicals chosen among phenyl, naphthyl or indenyl, and they can be substituted by one or more halogen atoms; heteroaryl radicals are 3-10-membered ring may contain one or more heteroatoms selected from among oxygen, sulfur and nitrogen, such as, in particular, thiazolyl, thienyl, pyrrolyl, pyridinyl, furyl, imidazolyl, oxazolyl, pyrazinyl, tetrazolyl; halogen radical represents a chlorine, iodine, fluorine, bromine radical; polycyclohexylene radicals chosen among adamantyl, hinokitiol, borneil, norbornanyl, bornene, norbornene; heteroaryl radical, condensed with (C1-C10-cycloalkyl, choose among indanyl, isopropanyl, Romania, 1,2,3,4-tetrahydroisoquinoline, 1,2,3,4-tetrahydroquinoline; heterocyclic radicals contain 1-2 heteroatoms selected from among oxygen, sulfur, nitrogen, and represent, in particular, piperidinyl, morpholinyl, pyrrolidinyl, imidazolidinyl, pyrazolidine, isothiazolinones, diazolidinyl, isoxazolidine, oxazolidine, piperazinil.

The compounds of formula (I) content is t one or more asymmetric carbon atoms and, consequently, it can be in the form of an isomer, racemate, enantiomers and diastereoisomers; they are also part of the invention, as well as mixtures thereof.

Of the compounds of formula (I)which are suitable according to the invention include the following compounds:

(2Z)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

ethyl-(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate;

ethyl(2Z)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate;

4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butane acid;

(2Z)-4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

(2E)-4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

(2Z)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butane acid;

(2E)-N-(6-chloro-1H-indazol-3-yl)-2-butanamide;

(2Z)-N-(6-chloro-1H-indazol-3-yl)-2-butanamide;

N-(6-chloro-1H-indazol-3-yl)-3-butenonitrile;

methyl-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate;

N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)butanamide;

(2E)-N-(6-bromo-1H-indazol-3-yl)-2-butanamide;

(2E)-N-(5-methyl-1H-indazol-3-yl)-2-butanamide;

(2Z)-N-(6-bromo-1H-indazol-3-yl)-2-butanamide;

(2Z)-N-(5-methyl-1H-indazol-3-yl)-2-butanamide;

N-(6-chloro-1 is-indazol-3-yl)-2-propenamide;

(2E)-N-[6-(trifluoromethyl)-1H-indazol-3-yl]-2-butanamide;

(2Z)-N-[6-(trifluoromethyl)-1H-indazol-3-yl]-2-butanamide;

ethyl-4-[[6-(trifluoromethyl)-1H-indazol-3-yl]amino]-4-oxobutanoate;

(2E)-N-[5-(trifluoromethyl)-1H-indazol-3-yl]-2-butanamide;

(2Z)-N-[5-(trifluoromethyl)-1H-indazol-3-yl]-2-butanamide;

N-[5-chloro-1H-indazol-3-yl]-2-butanamide;

N-[4-chloro-1H-indazol-3-yl]butanamide;

N-[6-(trifluoromethyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]propanamide;

N-[5-(trifluoromethyl)-1H-indazol-3-yl]butanamide;

N-[5-nitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-1H-indazol-3-yl]butanamide;

N-[6-(3-pyridyl)-1H-indazol-3-yl]butanamide;

N-[4-iodine-1H-indazol-3-yl]butanamide;

N-[6-phenyl-1H-indazol-3-yl]butanamide;

N-[6-bromo-5,7-dinitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-7-nitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-5-nitro-1H-indazol-3-yl]butanamide;

N-[6-(furan-3-yl)-1H-indazol-3-yl]butanamide;

N-[6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]benzolamide;

N-[6-(3,5-differenl)-1H-indazol-3-yl]butanamide;

N-[6-(3-thiophenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2-thiopheneacetic;

N-[5-[[3-(forfinal)sulfonyl]amino]-1H-indazol-3-yl]benzamide;

N-[6-(2-chlorophenyl)-1H-indazol-3-yl]butanamide;

N-[6-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-ethylphenyl)-1H-shall indazol-3-yl]butanamide;

N-[6-(4-ethenylene)-1H-indazol-3-yl]butanamide;

N-[6-(4-pyridyl)-1H-indazol-3-yl]butanamide;

N-[6-(phenylmethyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-AMINOPHENYL)-1H-indazol-3-yl]butanamide;

N-[6-(1-morpholino)-1H-indazol-3-yl]butanamide;

N-[6-[(4-phenylethynyl)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-(2-propenyl)-1H-indazol-3-yl]butanamide;

N-[5-amino-1H-indazol-3-yl]butanamide;

N-[6-bromo-5-chloro-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-bromo-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-nitro-1H-indazol-3-yl]butanamide;

N-[6-(4-hydroxyphenyl)-5-bromo-1H-indazol-3-yl]butanamide;

N-[6-(4-hydroxyphenyl)-5-(phenylamino)-1H-indazol-3-yl]butanamide;

N-[6-(4-hydroxyphenyl)-5-(2-phenylethenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-hydroxyphenyl)-5-phenylcarbamoyl-1H-indazol-3-yl]butanamide;

N-[6-(4-hydroxyphenyl)-5-[3-(dimethylamino)PROPYNYL]-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-3-thiophencarboxylic;

N-[6-chloro-1H-indazol-3-yl]-2-pyridineacetic;

N-[6-chloro-1H-indazol-3-yl]-3-pyridinecarboxamide;

N-[6-chloro-1H-indazol-3-yl]benzoylacetone;

N-[6-chloro-1H-indazol-3-yl]benzoylpropionic;

N-[6-chloro-1H-indazol-3-yl]-3-pyridineacetic;

N-[6-chloro-1H-indazol-3-yl]-2-chloracetamide;

N-[6-chloro-1H-indazol-3-yl]-4-morpholinoethyl;

N-[6-chloro-1H-indazol-3-yl]-1-piperazineethanol;

N-[6-chloro-1H-indazol-3-yl]-4-[(2-methoxyethyl)amino]cyclohexanecarboxylic;

4-amino--[6-chloro-1H-indazol-3-yl]-1-piperazinecarboxamide;

N-[6-chloro-1H-indazol-3-yl]-4-morpholinylcarbonyl;

their isomers, their mixtures, their racemates, the enantiomers, diastereoisomers, tautomers and their pharmaceutically acceptable salts;

and, in particular, the following connections:

(2Z)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

ethyl-(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate;

4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butane acid;

(2Z)-4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid;

4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butane acid;

(2E)-N-(6-chloro-1H-indazol-3-yl)-2-butanamide;

N-(6-chloro-1H-indazol-3-yl)-3-butenonitrile;

methyl-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate;

N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)butanamide;

(2E)-N-(6-bromo-1H-indazol-3-yl)-2-butanamide;

(2E)-N-(5-methyl-1H-indazol-3-yl)-2-butanamide;

N-(6-chloro-1H-indazol-3-yl)-2-propenamide;

(2E)-N-(6-(trifluoromethyl)-1H-indazol-3-yl)-2-butanamide;

ethyl-4-[[6-(trifluoromethyl)-1H-indazol-3-yl]amino]-4-oxobutanoate;

(2E)-N-(5-(trifluoromethyl)-1H-indazol-3-yl)-2-butanamide;

N-[5-chloro-1H-indazol-3-yl]-2-butanamide;

N-[4-chloro-1H-indazol-3-yl]-2-butanamide;

N-[6-(trifluoromethyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]propanamide;

N-[5-(trifluoromethyl)-1H-indazol-3-yl]butanamide;

N-[5-nitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-1H-indazol-3-yl]butanamide;

N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide;

N-[6-(3-pyridinyl)-1H-indazol-3-yl]butanamide;

N-[4-iodine-1H-indazol-3-yl]butanamide;

N-[6-phenyl-1H-indazol-3-yl]butanamide;

N-[6-bromo-5,7-dinitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-7-nitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-5-nitro-1H-indazol-3-yl]butanamide;

N-[(6-furan-3-yl)-1H-indazol-3-yl]butanamide;

N-[6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]benzolamide;

N-[6-(3,5-differenl)-1H-indazol-3-yl]butanamide;

N-[6-(3-thienyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2-thiopheneacetic;

N-[5-[[(3-forfinal)sulfonyl]amino]-1H-indazol-3-yl]benzamide;

N-[6-(2-phenylethyl)-1H-indazol-3-yl]butanamide;

N-(6,7-debtor-1H-indazol-3-yl)butanamide;

N-[6-(4-methoxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-methylthiophenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-trifloromethyl)-1H-indazol-3-yl]butanamide;

N-[6-(1-propenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2-pyridinecarboxamide;

N-[6-(4-forfinal)-1H-indazol-3-yl]butanamide;

N-[6-[4-(1,1-dimethylethyl)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-bromo-7-amino-1H-indazol-3-yl]butanamide;

N-[6-[4-(trifluoromethyl)phenyl]-1H-indazol-3-yl]butanamide;

-[6-(4-were)-1H-indazol-3-yl]butanamide;

N-[6-(3,5-dichlorophenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl] - for 3,5-dichlorobenzamide;

N-[6-(4-chlorophenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]benzoyltrifluoroacetone;

N-[6-chloro-1H-indazol-3-yl]benzoylpropionic;

N-[6-(4-ethylphenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-pyridinyl)-1H-indazol-3-yl]butanamide;

N-[5-amino-1H-indazol-3-yl]butanamide;

N-[5-bromo-6-chloro-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2-thiophencarboxylic;

N-[6-chloro-1H-indazol-3-yl]-2-methylpropanamide;

4-chloro-N-[6-chloro-1H-indazol-3-yl]butanamide;

N-[5-phenyl-6-chloro-1H-indazol-3-yl]butanamide;

N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide;

N-[5-bromo-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-nitrophenyl)-1H-indazol-3-yl]butanamide;

N-[6-(2-chlorophenyl)-1H-indazol-3-yl]butanamide;

N-[6-[3-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-(3-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-pyridinyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(3-furanyl)-1H-indazol-3-yl]butanamide;

N-[6-[2-chloro-4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5,6-dibromo-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2,2,3,3,4,4,4-getattributename;

N-[6-chloro-5-(4-forfinal)-1H-indazol-3-yl]butanamide;

N-[6-(4-AMINOPHENYL)-1H-indazol-3-yl]butanamide;/p>

N-[6-[4-(dimethylamino)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-4-methyl-1-piperazineethanol;

N-[6-chloro-1H-indazol-3-yl]-1-piperidineacetate;

N-(6-chloro-1H-indazol-3-yl)-4-morpholinoethyl;

N-(6-chloro-1H-indazol-3-yl)-1H-1,2,4-triazole-1-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-2-(cyclohexylamino)ndimethylacetamide;

2-[(phenylmethyl)amino]-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-1H-azepin-1-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-1-piperazineethanol;

N-(6-chloro-1H-indazol-3-yl)-2-[[3-(dimethylamino)propyl]amino]-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)thiomorpholine-4-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-1-pyrrolidineethanol;

N-(6-chloro-1H-indazol-3-yl)-2-[[2-(dimethylamino)ethyl]amino]-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-1-cyclopropanecarbonitrile-acetate;

N-(6-chloro-1H-indazol-3-yl)-1-cyclopropylbenzene;

N-(6-chloro-1H-indazol-3-yl)-2-(2-diethylaminoethylamine)-acetamidocinnamate;

N-(6-chloro-1H-indazol-3-yl)-2-(2-diethylaminoethylamine)ndimethylacetamide;

N-[5,6-diphenyl-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-were)-1H-indazol-3-yl]butanamide;

N-[5-phenyl-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide;

N-[5-phenyl-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-pyridinyl)-1H-indazol-3-yl]butanamide;

N-[5-(4-AMINOPHENYL)-6-chloro-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-ethylphenyl)-1H-indazol-3-and the]butanamide;

N-[6-chloro-5-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5,6-bis[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide;

N-[5,6-bis(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5-(3-furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide;

N-[5-(3-furanyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5-(4-ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide;

N-[5-(4-ethylphenyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]-butanamide;

N-[5-(3-pyridinyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide;

N-[5-(3-pyridinyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]-butanamide;

N-[5-(2-furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide;

N-[5-(2-furanyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-(5-bromo-6-chloro-7-nitro-1H-indazol-3-yl)butanamide;

N-(5-bromo-6,7-debtor-1H-indazol-3-yl)butanamide;

N-[6-(4-cyanophenyl)-1H-indazol-3-yl]butanamide;

N-(6,7-debtor-5-nitro-1H-indazol-3-yl)butanamide;

N-(6,7-debtor-5-phenyl-1H-indazol-3-yl)butanamide;

N-[6-(6-hydroxypyridine-3-yl)-1H-indazol-3-yl]butanamide;

N-[6-(3,4-dihydroxyphenyl)-1H-indazol-3-yl]butanamide-acetate;

N-[6-(3,4-dihydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[7-fluoro-5-nitro-6-[2-(phenylethyl)amino]-1H-indazol-3-yl]-butanamide;

N-(7-fluoro-5-nitro-6-morpholino-1H-indazol-3-yl)butanamide;

N-(7-fluoro-5-amino-6-morpholino-indazol-3-yl)butanamide;

N-(5-bromo-7-fluoro-6-morpholino-1H-indazol-3-yl)butanamide;

N-[7-fluoro-6-(trifluoromethyl)-1H-indazol-3-yl]butanamide;

N-(6-bromo-4,5,7-Cryptor-1H-indazol-3-yl)butanamide;

N-[6-(6-aminopyridine-3-yl)-1H-indazol-3-yl]butanamide-acetate;

N-[6-(6-aminopyridine-3-yl)-1H-indazol-3-yl]butanamide;

2-chloro-N-(6,7-debtor-1H-indazol-3-yl)ndimethylacetamide;

N-(6,7-debtor-1H-indazol-3-yl)-1-piperidineacetate;

their isomers, their mixtures, their racemates, the enantiomers, diastereoisomers, tautomers and their pharmaceutically acceptable salts.

The invention relates also to pharmaceutical compositions containing as an active beginning derivative of the formula (I)in which:

R means O, S or NH;

R3 means a radical (C1-C6)-alkyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl; aryl or heteroaryl condensed with (C1-C10-cycloalkyl; heterocyclic residue, cycloalkyl, substituted, politically, alkenyl, quinil, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R4, R5, R6 and R7, which ezavisimo from each other, choose among the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, -O-SO2R8, -SO2-O-R8, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, quinil, substituted, politically, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

its isomers, mixtures, racemates, the enantiomers, diastereoisomers, tautomers and their pharmaceutically acceptable salts.

In particular, the present invention relates to the use of derivatives aminoindazole formula (I), in which:

R means O, S or NH;

R3 means a radical (C1-C6)-alkyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, cycloalkyl, alkenyl, quinil, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R4 and R7 means a hydrogen atom;

R5, R6, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, -O-SO2R8, -SO2-O-R8, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, cycloalkyl, heterocyclic residue, alkenyl, quinil, substituted, politically, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2 -O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

their isomers, their mixtures, their racemates, enantiomers, diastereoisomers, tautomers and their pharmaceutically acceptable salts.

And preferably, the present invention relates to the use of derivatives aminoindazole formula (I)in which:

R means O;

R4 and R7 denote H;

R3 means a radical (C1-C6)-alkyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR8, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, C(S)NR8R9, NHC(S)R8, -O-SO2R8, -SO2-O-R8, aryl, heteroaryl, formyl, trifloromethyl, cryptomelane, cryptometer;

R5 and R6, independently from each other, you who eraut among the following radicals: hydrogen atom, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, trifloromethyl, cryptometer;

their racemates, enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts.

In the above and the following definitions and alkyl (C1-C6)-alkyl radicals contain 1 to 6 carbon atoms in whether anoy or branched chain; alkeneamine radicals contain 1 to 6 carbon atoms and 1-3 paired or no double bond in a linear or branched chain; alkyline radicals contain 1 to 6 carbon atoms and 1-3 paired or not triple bond in a linear or branched chain; aryl radicals chosen among phenyl, naphthyl or indenyl, and they can be substituted by one or more halogen atoms; heteroaryl radicals are 3-10 membered ring may contain one or more heteroatoms selected from among oxygen, sulfur and nitrogen, such as, in particular, thiazolyl, thienyl, pyrrolyl, pyridinyl, furyl, imidazolyl, oxazolyl, pyrazinyl, tetrazolyl; halogen radical represents a chlorine, iodine, fluorine, bromine radical; polycyclohexylene radicals chosen among adamantyl, hinokitiol, borneil, norbornanyl, bornene, norbornene; heteroaryl radical, condensed with (C1-C10-cycloalkyl, choose among indanyl, isopropanyl, Romania, 1,2,3,4-tetrahydroisoquinoline, 1,2,3,4-tetrahydroquinoline; heterocyclic radicals contain 1-2 heteroatoms selected from among oxygen, sulfur, nitrogen, and represent, in particular, piperidinyl, morpholinyl, pyrrolidinyl, imidazolidinyl, pyrazolidine, isothiazolinones, diazolidinyl, isoxazolidine, oxazolidine, piperazinil.

Derivatives of the formula (), in which R=O, can be obtained by acylation of the corresponding 3-amino or by a carboxylic acid, acid anhydride, or by reacting with an acid in the presence of activator.

According to route (a), the reaction is carried out in the presence of a base, such as pyridine, triethylamine, diisopropylethylamine; the reaction may start at a temperature of 0aboutFrom and after adding the carboxylic acid, osushestvlya stirring at room temperature (G. DAIDONE, Heterocycles,43(11), 2385-2396 (1996)) or heated, if necessary.

According to path (b), the reaction may be carried out at the boiling point under reflux inert solvent, such as xylene, or tetrahydrofuran (F. ALBERICIO, Synth. Commun.,31(2), 225-32 (2001)), or dichloromethane (G. PROCTER, Tetrahedron,51(47), 12837-842 (1995)), or at the very anhydride.

According to path (C), the reaction is carried out in the presence of an activator such as one carbodiimide (N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide) (M.C. DESAI, Tetrahedron Lett.,34, 7685 (1993)), or in the presence of hydroxybenzotriazole and dimethylaminopyridine (J.P. GAMET, Tetrahedron,40, 1995 (1984); K. BARLOS, J. Org. Chem.,50, 696 (1985)), or according to well known methods of bonding in the chemistry of peptides (M. BODANSZKY, Principles of Peptide Synthesis, ed. Springer, new York, NY, S. 9-58 (198)) or formation of amide linkages.

When in the compound of formula (I) R3 at the end carbon atom include an acid residue, the latter can be obtained by the condensation reaction of a cyclic anhydride, such as maleic anhydride, succinic anhydride, phthalic anhydride, or by the condensation reaction of an ester of a carboxylic acid, then saponification of the latter according to the following scheme:

Ester group can be recovered by methods known to the person skilled in the art, for example, using tetrahydroborate sodium in methanol or sociallyengaged in dioxane or tetrahydrofuran, upon receipt of the corresponding alcohol according to the following scheme:

In the case of derivatives of formula (I) in which R=S, this latter is obtained by acarnania corresponding oxo derivatives using reagent Lawesson (R. OLSSON, Tetrahedron Lett.,41(41), 7947-50 (2000)) or by treatment with pentasulfide phosphorus in pyridine or toluene (J. VOSS, Justus Liebig Ann. Chem.,716, 209 (1968); O. TSUGE, Chem. Lett., 1369 (1980)).

Derivatives of formula (I)in which R=NH can be obtained by reaction of 3-amino-1H-indazols with nitrile or salt Merweein (S. PATAI, "The Chemistry of amidines and imidates", J. Wiley and Sons, (1975), S. 283).

3-Amino-1H-indazols formula (II) can be obtained by p the action of 2-perbenzoate with hydrazinehydrate or hydrazinecarboxamide boiling under reflux for 2-18 hours in alcohol type ethanol or n-butanol according to (R.F. KALTENBACH, Bioorg. Med. Chem. Lett.,9(15), 2259-62 (1999)):

Compounds in which R4, R5, R6 and R7, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, -O-SO2R8, -SO2-O-R8, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, cycloalkyl, alkenyl, quinil, substituted, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer; can be obtained by reactions carried out in the chemistry of palladium according to Suzuki (A. SUZUKI, Pure Appl. Chem.,63, 419-422 (1991), Stille (J. STILLE, Angew. Chem. Int. Ed.,25, 508-524 (1986), Heck (R.F. HECK, Org. React.,27, 345-390 (1982), Sonogashira (K. SONOGASHIRA, Synthesis, 777 (1977), Buckwald (S.L. BUCKWALD, Acc. Chem. Re.,31, 805 (1998)), on the basis of the corresponding halogen derivatives.

For this purpose it is necessary to protect reactive functional groups. Thus, functional groups, HE, SH, COOH, NH2should be protected the us before carrying out binding assays. Protective groups introduced by any means known to the person skilled in the art, and, in particular, the methods described in the manual T.W.GREENE "Protective groups in Organic Synthesis", J. Wiley-Interscience Publication (1991). Preferred is the protection of the nitrogen atom in position 1 groups, such as tert-butoxycarbonyl, or by using the silicon-containing derivatives. Preferably choose Siciliano group, such as tert-butyldimethylsilyl, triisopropylsilyl, which can be removed using fluoride anions or with acetic acid, and in particular trimethylsilylamodimethicone group, tsepliaeva using tetrabutylammonium at the boiling point under reflux in a solvent such as tetrahydrofuran, dioxane (J.P. WHITTEN, J. Org. Chem.,51, 1891 (1986); B.H. LIPSHUTZ, Tetrahedron Lett., 4095 (1986)).

Derivatives, secured in position 1 trimethylsilylamodimethicone, produced by entering into interaction source connection trimethylsilylamodimethicone in the presence of sodium hydride in a solvent such as dimethylformamide, at room temperature (J.P. WHITTEN, J. Org. Chem.,51, 1891 (1986); M.P. EDWARDS, Tetrahedron,42, 3723 (1986)).

Similarly, the nitrogen-containing NH group at position 1 of indazole protecting groups, such as tosyl, carbamate, benzyl or siciliane derivatives. For example, in the case where you want to make Holy is the help support with palladium halogen derivatives in position 6, need to protect the nitrogen atom in position 1, as indicated below (X = Cl, Br, I):

The removal of the protective group is carried out by methods known to the person skilled in the art and described in the manual T.W. GREENE, "Protective groups in Organic Synthesis", J. Wiley-Interscience Publication (1991). For example, if the protective group at position 1 is trimethylsilylethynyl, you can remove it by entering into interaction with tetrabutylammonium, as shown below:

When one of the groups R4, R5, R6 and R7 involved in the binding used in the chemistry of palladium, itself contains a reactive group such as hydroxyl, amino, Tolna group, carboxyl, or, in General, includes a heteroatom, these latter also must be protected prior to making binding with palladium. For example, the phenolic group is introduced into a protected form (for example, O-benzyl), based on chlorinated, and the nitrogen atom in position 1 protect, as explained earlier:

The benzyl group is then removed, for example, by treatment with trimethylsilylimidazole at the boiling point under reflux in acetonitrile. Protection can also be implemented using trimethylsilylamodimethicone group, tsepliaeva using tetrabutylammonium the ri boiling point under reflux in a solvent, such as tetrahydrofuran, dioxane (J.P. WHITTEN, J. Org. Chem.,51, 1891 (1986); B.H. LIPSHUTZ, Tetrahedron Lett., 4095 (1986)).

Some derivatives can be subjected to reactions of electrophilic substitution, nitration, halogenation, acylation according to the Friedel-Crafts.

For example, nitration of substituted at position 6 derivatives (such as described above) can be implemented in well-known ways, such as with nitric acid in acetic acid or detroitmetroairport in solvents such as acetonitrile (J. L. DUFFY, J. Org. Chem.,56, 3006-3009 (1991)). Of course, the nitro-group can be recovered by using hydrogen in the presence of palladium (B. BARAGATTI, Eur. J. Med.,35(10), 949-955 (2000)) or by using chloride of divalent tin in the presence of hydrochloric acid (R.P. DIXON, Org. Prep. Proced. Int.,32(6), 573-577 (2000)), using sulfate ferrous iron in the presence of ammonium hydroxide (S. CASTELLANO, J. Heterocycl. Chem.,37(6), 1539-1542 (2000)). Thus the released amino group can be allerban or may be subjected to diazotization to implement the response Sandmeyer-Gatterman (substitution on Cl, Br, I, CN, RS, OH) (H.H. HODGSON, Chem. Rev.,40, 251-277 (1947); T. SUGAYA, Synthesis, 73-76 (1994)), and the obtained diazonium derivatives (N. SUZUKI, J. Chem. Soc. Perkin Tr., 645 (1987)) or halogen derivatives again, as in the previous case, can takes the diamonds in the reaction, carried out in the chemistry of palladium.

Derivatives of 3-aminoindazole formula (II):

in which:

R4, R5, R6 and R7, independently of one another, chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, OH, COOH, C(O)OR8, -O-C(O)R8, NR8R9, NHC(O)R8, C(O)NR8R9, NHC(S)R8, C(S)NR8R9, SR8, S(O)R8, SO2R8, NHSO2R8, SO2NR8R9, -O-SO2R8, -SO2-O-R8, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, (C1-C6-alkoxyl, aryl, aryl-(C1-C6)-alkyl, heteroaryl, heteroaryl-(C1-C6)-alkyl, heterocyclic residue, cycloalkyl, alkenyl, quinil, substituted, politically, and these radicals are unsubstituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2, OH, OR10, COOH, C(O)OR10, -O-C(O)R10, NR10R11, NHC(O)R10, C(O)NR10R11, NHC(S)R10, C(S)NR10R11, SR10, S(O)R10, SO2R10, NHSO2R10, SO2NR10R11, -O-SO2R10, -SO2-O-R10, aryl, heteroaryl, formyl, trifloromethyl, cryptometer;

R8, R9, R10, R11, independently of one another, mean a hydrogen atom, (C1-C6)-alkyl, aryl, alkenyl, quinil, heteroaryl, which themselves are unsubstituted or substituted by one or more substituents selected among halogen, (C1-C6)-alkyl, (C1-C6)-alkoxyl, CN, NO2, NH2, OH, COOH, COO-alkyl, CONH2, formyl, triforma the sludge, cryptometer;

their isomers, their mixtures, their racemates, the enantiomers, diastereoisomers, tautomers suitable as intermediates for obtaining derivatives of General formula (I).

Compounds of General formula (II) or its pharmaceutically acceptable salt can also be used to produce medicines and pharmaceutical compositions for the same testimony that is given to compounds of the formula (I).

Of the compounds of the formula (II) include the following products:

3-amino-5-bromo-1H-indazol;

3-amino-6-bromo-1H-indazol;

3-amino-5-methyl-1H-indazol;

3-amino-6-(trifluoromethyl)-1H-indazol;

3-amino-5-(trifluoromethyl)-1H-indazol;

3-amino-4-chloro-1H-indazol;

3-amino-5-nitro-1H-indazol;

3-amino-6-(3-pyridinyl)-1H-indazol;

3-amino-4-iodine-1H-indazol;

3-amino-6-phenyl-1H-indazol;

3-amino-6-bromo-5,7-dinitro-1H-indazol;

3-amino-6-bromo-7-nitro-1H-indazol;

3-amino-6-bromo-5-nitro-1H-indazol;

3-amino-6-(furan-3-yl)-1H-indazol;

3-amino-6-[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-6-(4-hydroxyphenyl)-1H-indazol;

3-amino-6-(3,5-differenl)-1H-indazol;

3-amino-6-(3-thienyl)-1H-indazol;

3-amino-5-[[(3-forfinal)sulfonyl]amino]-1H-indazol;

3-amino-6-(2-phenylethyl)-1H-indazol;

3-amino-6,7-debtor-1H-indazol;

3-amino-6-(4-methoxyphenyl)-1H-indazol;

3-amino-6-(4-methylthiophenyl)-1H-indazol;

<> 3-amino-6-(4-trifloromethyl)-1H-indazol;

3-amino-6-(1-propenyl)-1H-indazol;

3-amino-6-(4-forfinal)-1H-indazol;

3-amino-6-[4-(1,1-dimethylethyl)phenyl]-1H-indazol;

3-amino-6-bromo-7-amino-1H-indazol;

3-amino-6-(4-were)-1H-indazol;

3-amino-6-(3,5-dichlorophenyl)-1H-indazol;

3-amino-6-(4-chlorophenyl)-1H-indazol;

3-amino-6-(4-ethylphenyl)-1H-indazol;

3-amino-6-(4-pyridinyl)-1H-indazol;

3-amino-5-amino-1H-indazol;

3-amino-5-bromo-6-chloro-1H-indazol;

3-amino-5-phenyl-6-chloro-1H-indazol;

3-amino-5-bromo-6-[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-5-bromo-6-(4-hydroxyphenyl)-1H-indazol;

3-amino-6-(4-nitrophenyl)-1H-indazol;

3-amino-6-(2-chlorophenyl)-1H-indazol;

3-amino-6-[3-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-6-(3-hydroxyphenyl)-1H-indazol;

3-amino-6-chloro-5-(4-pyridinyl)-1H-indazol;

3-amino-6-chloro-5-(3-furanyl)-1H-indazol;

3-amino-6-[2-chloro-4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-6-(2-chloro-4-hydroxyphenyl)-1H-indazol;

3-amino-5,6-dibromo-1H-indazol;

3-amino-6-chloro-5-(4-forfinal)-1H-indazol;

3-amino-6-(4-AMINOPHENYL)-1H-indazol;

3-amino-6-[4-(dimethylamino)phenyl]-1H-indazol;

3-amino-6-chloro-1H-indazol;

3-amino-5,6-diphenyl-1H-indazol;

3-amino-6-chloro-5-(4-were)-1H-indazol;

3-amino-5-phenyl-6-[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-5-phenyl-6-(4-hydroxyphenyl)-1H-indazol;

3-amino-5-(4-AMINOPHENYL)-6-chlorine is-1H-indazol;

3-amino-6-chloro-5-(4-ethylphenyl)-1H-indazol;

3-amino-6-chloro-5-[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-6-chloro-5-(4-hydroxyphenyl)-1H-indazol;

3-amino-5,6-bis[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-5,6-bis(4-hydroxyphenyl)-1H-indazol;

3-amino-5-(3-furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-5-(3-furanyl)-6-(4-hydroxyphenyl)-1H-indazol;

3-amino-5-(4-ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-5-(4-ethylphenyl)-6-(4-hydroxyphenyl)-1H-indazol;

3-amino-5-(3-pyridinyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-5-(3-pyridinyl)-6-(4-hydroxyphenyl)-1H-indazol;

3-amino-5-(2-furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol;

3-amino-5-(2-furanyl)-6-(4-hydroxyphenyl)-1H-indazol;

3-amino-5-bromo-6-chloro-7-nitro-1H-indazol;

3-amino-5-bromo-6,7-debtor-1H-indazol;

3-amino-6-(4-cyanophenyl)-1H-indazol;

3-amino-6,7-debtor-5-nitro-1H-indazol;

3-amino-6,7-debtor-5-phenyl-1H-indazol;

3-amino-6-(6-hydroxypyridine-3-yl)-1H-indazol;

3-amino-6-(3,4-dihydroxyphenyl)-1H-indazol;

3-amino-7-fluoro-5-nitro-6-[2-(phenylethyl)amino]-1H-indazol;

3-amino-7-fluoro-5-nitro-6-morpholino-1H-indazol;

3-amino-7-fluoro-5-amino-6-morpholino-1H-indazol;

3-amino-5-bromo-7-fluoro-6-morpholino-1H-indazol;

3-amino-7-fluoro-6-(trifluoromethyl)-1H-indazol;

3-amino-6-bromo-4,5,7-Cryptor-1H-indazol;

3-amino-6-(6-aminopyridine-3-yl)-1H-indazol.

Compounds of formulas is (I) allocate, and they can be cleaned by the usual known methods, for example by crystallization, chromatography or extraction.

The compounds of formula (I), if necessary, can be transformed into additive salts of inorganic or organic acids by exposure to this acid in an organic solvent, such as alcohol, ketone, simple ether or a chlorinated solvent. These salts also form part of the invention.

As examples of pharmaceutically acceptable salts include salts: bansilalpet, hydrobromide, hydrochloride, citrate, aconsultant, fumarate, gluconate, Iodate, maleate, isetionate, methanesulfonate, methylene-bis-b-xinafoate, nitrate, oxalate, pamoate, phosphate, salicylate, succinate, sulfate, tartrate, theophyllinate and p-toluensulfonate.

The compounds of formula (I) are inhibitors of kinases, and thus suitable for the prevention and treatment of neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontoparietal dementia, corticobasal degeneration, diseases of the Peak, cerebrovascular disorders, cranial and spinal injuries and peripheral neuropathies, obesity, essential hypertension, cardiovascular atherosclerotic diseases, polycystic ovary syndrome, syndrome X, immunodeficiency and cancer.

Their activity, the mouth is Owlery by determining the inhibition of phosphorylation of tau-protein in slices of cerebral cortex of adult rats.

Slices of the cerebral cortex thickness of 300 μm get from male OFA rats (Iffa-Credo) at the age of 8-10 weeks, murdered by decapitation. They incubated in 5 ml of modified according to the method of Dulbecco eagle medium containing pyruvate and glucose 4.5 g/l, at a temperature of 37aboutC for 40 minutes. The slices are then washed 2 times with medium, distributed in a microtube (50 ál 500 ál medium with the test compounds or without them) and incubated at temperature 37aboutWith shaking. Two hours later, the experiment is stopped by centrifugation. The slices are lysed irradiated with ultrasound and centrifuged at acceleration 18300g for 15 minutes at a temperature of 4aboutC. the Concentration of protein in the supernatant is determined using the standard test for the quantitative determination (ICA Protein Assay, Pierce)based on the Lowry method.

The samples, previously denatured for 10 minutes at a temperature of 70aboutWith share on vertical gel 4-12 % Bis-Tris, in the presence of buffer 4-morpholinepropanesulfonic-sodium dodecyl sulphate and concentrated electroblotting on the nitrocellulose. Monomachine carried out using monoclonal antibody AD2, which specifically recognize phosphorylated epitopes Ser396/404 tau-protein. Immunoreactive proteins visualize by adding Vtorov the antibodies, directed against mouse IgG and conjugated to peroxidase and chemiluminescent substrate. Received autoradiogram finally quantificare using the software package "Gene Tools Syngene (GeneGnome, Ozyme) to determine the concentration that causes 50 %inhibition (CI50).

The compounds of formula (I) have a very useful activity and, in particular, some compounds have CI50below 100 µmol.

The following examples explain the invention without limiting its scope.

Example 1

(2Z)-4-[(6-Chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid

To 1 g of 6-chloro-1H-indazol-3-amine in 30 cm3o-xylene add 585 mg pre-crushed maleic anhydride. The reaction medium is refluxed at a temperature of 145aboutC for 10 minutes, then cooled using a water bath. The insoluble part is filtered off and washed successively with 2 times 25 cm3ethyl acetate, then 2 times to 25 cm3diisopropyl ether. The solid is then dried under reduced pressure (90 PA; 50aboutC)receiving 1 g of 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid (Z-form) in the form of yellow crystals, melting at 230aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 6,38 (d, J=12 Hz, 1H), 6,60 (d, J=12 is C, 1H), 7,13 (DD, J= 9 and 1.5 Hz, 1H), 7,55 (d, J=1.5 Hz, 1H), 7,94 (d, J=9 Hz, 1H), 10,99 (USS, 1H), 12,60-13,40 (array ush., 1H), 12,92 (array, 1H).

Example 2

Ethyl-(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate

To 1 g of 6-chloro-1H-indazol-3-amine in 50 cm3dichloromethane add 865 mg of monoethylfumarate. Then give 1.4 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and stirred for 30 minutes at a temperature of 20aboutC. Washed with 50 cm3distilled water, then with 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered, then evaporated under reduced pressure (2 kPa; 40aboutC). Receive 2 g of resinous mass brick color, which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume) and collecting fractions of 40 cm3. The fractions containing the desired product are pooled and then evaporated under reduced pressure (2 kPa) at a temperature of approximately 40aboutC. After drying (90 PA; 45aboutC) get 900 mg of ethyl-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate (form E), melting at 220aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,50-2,75 (m, 4H), 7,07 (DD, J=8.5 and 1.5 Hz, 1H), 7,52(d, J=1.5 Hz, 1H), 7,83 (d, J=8.5 Hz, 1H), 11,50 (ush., 1H), 12,19 (array ush., 1H), was 12.75 (array, 1H).

Example 3

4-[(6-Chloro-1H-indazol-3-yl)amino]-4-oxo-2-butane acid

To 500 mg of 6-chloro-1H-indazol-3-amine in 30 cm3o-xylene add 300 mg of succinic anhydride. The reaction medium is refluxed at a temperature of 145aboutC for 16 hours, then heating stopped and allowed to cool to room temperature, 20aboutC. the Reaction medium is then filtered through a porous glass filter (= a porous glass filter); solid handles with 20 cm3ethyl acetate and 30 cm310 %-aqueous solution of sodium bicarbonate. The organic phase is dried over magnesium sulfate, filtered, then evaporated in already described conditions. The thus obtained crystals white mixed with 30 cm310 %-aqueous solution of sodium bicarbonate for 20 minutes. Small insoluble portion removed by filtration and the filtrate is acidified with 12 N. hydrochloric acid; the precipitated precipitate is washed with 2 times 10 cm3distilled water, once with 5 cm3acetone and 2 x 10 cm3diisopropyl ether. The solid is then dried under reduced pressure at a temperature of approximately 40aboutWith, and then purified by chromatography under a pressure of argon to 0 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 99:1 by volume) and collecting fractions of 20 cm3. The fractions containing the desired product are pooled and then evaporated under these conditions. The resulting product is treated with 10 cm3ethyl acetate, filtered off on a glass Frit and washed with 2 times 5 cm3ethyl acetate, then with 20 cm3diethyl ether. Dried under reduced pressure overnight (90 PA; 40aboutC) and thus receive the 110 mg of 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butane acid in a solid white color, melting at 200aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,50-2,75 (m, 4H), 7,07 (DD, J=8.5 and 1.5 Hz, 1H), 7,52 (d, J=1.5 Hz, 1H), 7,83 (d, J=8.5 Hz, 1H), 11,50 (ush., 1H), 12,19 (array ush., 1H), was 12.75 (array, 1H).

Example 4

(2Z)-4-[(5-Bromo-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid

To 500 mg of 5-bromo-1H-indazol-3-amine, obtained as described in U.S. patent 3133081, 20 cm3toluene added 350 mg of maleic anhydride. The medium is refluxed at a temperature of 110aboutC for 1 hour. Then the heating is stopped and stirred at a temperature of 19aboutWith in 12 hours. The precipitation is filtered off on a glass Frit and washed with 20 the m 3diisopropyl ether, 2 cm3ethyl acetate and 2 cm3dichloromethane. After drying (90 PA; 45about(C) receive 448 mg of 4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid, form Z, in the form of a solid yellow color, melting at 172aboutC.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6), d in ppm: 6,38 (d, J=12 Hz, 1H), 6,62 (d, J= 12 Hz, 1H), 7,49 (m, 2H), 8,15 (ush., 1H), 10,95 (ush., 1H), 12,70-13,30 (array ush., 1H), 12,98 (array, 1H).

Example 5

(2E)-4-[(6-Chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid

To 280 mg of ethyl-(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate described in example 2, 25 cm3ethanol add 0.95 cm31 n sodium hydroxide solution. The reaction medium is then heated at a temperature of 50aboutC for 2 hours, then add another 1 equivalent of 1 n sodium hydroxide solution. Temperature 50aboutWith support for 30 minutes and the heating is stopped. At a temperature of 20aboutWith the medium is neutralized with 1N hydrochloric acid, then concentrated under reduced pressure (2 kPa; 40aboutC). The thus obtained solid residue is treated with 25 cm3tetrahydrofuran (THF, 50 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is washed with 30 cm3saturated aqueous solution of chloride of soda is I, then dried over magnesium sulfate. Filtered and evaporated under these conditions. The residue is treated with 10 cm3ethyl acetate, the insoluble part is filtered off, then washed with 5 cm3ethyl acetate and 10 cm3diethyl ether and dried under reduced pressure (90 PA; 50aboutC). Obtain 155 mg of 4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acid (form E) form solid of light yellow color, melting at 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 6.75 (d, J=15,5 Hz, 1H), 7,11 (DD, J=9 and 2 Hz, 1H), 7,27 (d, J= 15,5 Hz, 1H), 7,55 (d, J= 2 Hz, 1H), of 7.96 (d, J= 9 Hz, 1H), 11,13 (ush., 1H), 12,40-13,10 (array ush., 1H), 12,94 (array, 1H).

Example 6

4-[(5-Bromo-1H-indazol-3-yl)amino]-4-oxo-2-butane acid

To 500 mg of 5-bromo-1H-indazol-3-amine, obtained as described in U.S. patent 3133081, 20 cm3toluene add 354 mg of succinic anhydride. The reaction medium is refluxed at a temperature of 110aboutWith over 13 hours. The precipitate is filtered off, then washed with 10 cm3diisopropyl ether and 10 cm3dichloromethane. The product is treated with 20 cm3saturated aqueous sodium hydrogen carbonate solution and acidified with 5 N. hydrochloric acid until pH = 9/10. The precipitation is filtered off and washed with 20 cm 3distilled water, then the solid is treated with 20 cm3of acetone. Is evaporated to dryness under reduced pressure (2 kPa; 40aboutC) and after drying (90 PA; 45about(C) obtain 270 mg of 4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butane acid in a solid white color, melting at 173aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,50-2,75 (m, 4H), 7,45 (ush., 2H), 8,02 (ush., 1H), 10,55 (array, 1H), 12,83 (array, 1H).

Example 7

(2E)-N-(6-Chloro-1H-indazol-3-yl)-2-butanamide

To a solution of 50 mg of 6-chloro-1H-indazol-3-amine in 5 cm3pyridine, cooled to a temperature of 6aboutTo add to 0.67 cm3the relocated crotolaria. Stirred for 10 minutes, then incubated with increasing temperature again until 19aboutWith over 22 hours. Reaction medium was then concentrated to dryness under reduced pressure (2 kPa; 40aboutC), then the residue is treated with 50 cm3of tetrahydrofuran and 25 cm3ethyl acetate. The organic phase is washed with 2 times 50 cm3distilled water, then with 50 cm3saturated aqueous solution of sodium chloride. Dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under these conditions. The resulting residue is purified by chromatography the od pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume) and collecting fractions of 20 cm3. The fractions containing the desired product are pooled and then evaporated in already described conditions. After drying (90 PA; 45about(C) receive 100 mg of N-(6-chloro-1H-indazol-3-yl)-2-butanamide, form E, in the form of a solid white color, melting at 226aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1,90 (l ush., J= 7 Hz, 3H), 6,27 (DD, J= 15 and 1.5 Hz, 1H), 6,88 (l kV, J=15 and 7 Hz, 1H), was 7.08 (DD, J= 9 and 2 Hz, 1H), 7,52 (d, J= 2 Hz, 1H), 7,92 (d, J= 9 Hz, 1H), 10,53 (array, 1H), 12,80 (array, 1H).

Example 8

6-Chloro-1-[(1,1-dimethylmethoxy)carbonyl]-1H-indazol-3-amine

To 1 g of 6-chloro-1H-indazol-3-amine in 30 cm3dichloromethane add 1.3 g of di-tert-BUTYLCARBAMATE and 10 mg dimethylaminopyridine. Stirred for 17 hours at a temperature of 19aboutC. the Reaction medium is evaporated to dryness in already described conditions, then the resulting residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) obtain 1.2 g of 6-chloro-1-[(1,1-dimethylmethoxy)carbonyl]-1H-ind is evil-3-amine in the form of a solid white color.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6), d in ppm: 1,61 (s, N), to 6.43 (ush., 2N), was 7.36 (DD, J= 9 and 1.5 Hz, 1H), 7,89 (d, J= 9 Hz, 1H), 7,97 (ush., 1H).

N-(6-Chloro-1-[(1,1-dimethylmethoxy)carbonyl]-1H-indazol-3-yl)-3-butanamide

To 1 g of 6-chloro-1-[(1,1-dimethylmethoxy)carbonyl]-1H-indazol-3-amine described above, in 40 cm3dichloromethane and 1.05 cm3triethylamine add 0,45 cm3pre-relocated crotolaria. Stirred for 16 hours at a temperature of 19aboutC. the Medium is then concentrated under reduced pressure (20 kPa; 40aboutC). The residue is treated with 100 cm3ethyl acetate and 50 cm3of distilled water. Then the organic phase is washed with 50 cm3saturated aqueous solution of sodium chloride. Dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated in the above-described conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume) and collecting fractions 15 cm3. The fractions containing the desired product are pooled and then evaporated under reduced pressure (2 kPa; 40aboutC). After drying (90 PA; 45about(C) receive 120 mg of N-(6-chloro-1-[(1,1-dimethylmethoxy)carbonyl]-1H-indazol-3-yl)-3-butanamide in view of the solid yellow color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 1.66 (s, N), 3,28 (l ush., J= 7.5 Hz, 2H), 5,20 (DD, J= 10.5 and 1.5 Hz, 1H), 5,26 (DD, J= 17 and 1.5 Hz, 1H), 6,02 (m, 1H), 7,43 (DD, J= 9 and 2 Hz, 1H), with 8.05 (d, J= 9 Hz, 1H), 8,12 (d, J= 2 Hz, 1H), 11,09 (array, 1H).

N-(6-Chloro-1H-indazol-3-yl)-3-butenonitrile

To 240 mg of N-(6-chloro-1-[(1,1-dimethylmethoxy)carbonyl]-1H-indazol-3-yl)-3-butanamide described above, add 10 cm34 n solution of hydrogen chloride in dioxane. Stirred for 17 hours at a temperature of 19aboutC. Vegascasinoonline the product is filtered on a glass Frit, washed with 2 times 5 cm3ethyl acetate and 2 times 5 cm3diethyl ether, then dried under reduced pressure (90 PA; 40aboutC). Thus receive 125 mg of N-(6-chloro-1H-indazol-3-yl)-3-butanamide as hydrochloride and melting at 150aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 3,22 (d, J= 7 Hz, 2H), 5,17 (l ush., J= 10.5 Hz, 1H), 5,23 (e ush., J= 18 Hz, 1H), 5,30-6,80 (array ush., 2N), of 6.02 (m, 1H), 7,07 (DD, J= 9 and 2 Hz, 1H), 7,52 (d, J= 2 Hz, 1H), 7,82 (d, J= 9 Hz, 1H), 10,50 (ush., 1H).

Example 9

Methyl-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate

To 3.5 g of methyl 4-chloro-4-oxobutanoate in 10 cm3dichloromethane at a temperature of 5aboutTo add 4 g of 6-chloro-1H-indazol-3-amine in 40 cm3pyridine. Stand upon reaching again the temperatures of the 19 aboutC for 19 hours. The reaction medium is evaporated under these conditions. The residue is treated with 75 cm3of tetrahydrofuran and 75 cm3ethyl acetate. Washed 3 times in 50 cm3of distilled water. Dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 40aboutC). The product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 6 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume) and collecting fractions of 50 cm3. The fractions containing the desired product are pooled and then evaporated under reduced pressure (2 kPa; 40aboutC). After drying (90 PA; 45about(C) receive 3 g methyl-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate in a solid white color, melting at 170aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,60 is 2.80 (m, 4H), 3,63 (s, 3H), was 7.08 (DD, J= 9 and 2 Hz, 1H), 7,52 (d, J= 2 Hz, 1H), 7,82 (d, J= 9 Hz, 1H), 10,52 (array, 1H), 12,77 (array ush., 1H).

Example 10

N-(6-Chloro-1H-indazol-3-yl)ndimethylacetamide

To 750 mg of 6-chloro-1H-indazol-3-amine in 10 cm3pyridine, after cooling the reaction medium to a temperature of 3aboutTo add 0,32 cm3previously surpassed acetylchloride. Then the environment is maintained at the actiuni again the temperature of the 19 aboutWith in 48 hours. The reaction medium is evaporated to dryness under reduced pressure (2 kPa; 40aboutC). The residue is treated with 75 cm3ethyl acetate and 50 cm3of distilled water. The organic phase is again washed with 50 cm3distilled water, then dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure. The resulting residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume) and collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 40aboutC). After drying (90 PA; 45aboutC) get 700 mg of N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, melting at 240aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2.13 in (s, 3H), was 7.08 (DD, J= 9 and 2 Hz, 1H), 7,52 (d, J= 2 Hz, 1H), 7,86 (d, J= 9 Hz, 1H), 10,45 (array, 1H), 12,50-13,10 (array ush., 1H).

Example 11

N-(6-Chloro-1H-indazol-3-yl)butanamide

To 750 mg of 6-chloro-1H-indazol-3-amine in 10 cm3pyridine, after cooling the reaction medium to a temperature of 3aboutTo add to 0.47 cm3butyrylcholine. Then the environment is maintained at achieving again the temperature of the 19aboutis within 14 hours. The reaction medium is evaporated to dryness under reduced pressure (2 kPa; 40aboutC). The residue is treated with 50 cm3ethyl acetate, 50 cm3of tetrahydrofuran and 50 cm3of distilled water. The organic phase is again washed with 50 cm3distilled water and 50 cm3saturated aqueous solution of sodium chloride, then dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure. The resulting residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume) and collecting fractions of 25 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 40aboutC). After drying (90 PA; 45about(C) receive 200 mg of N-(6-chloro-1H-indazol-3-yl)butanamide in a solid white color, melting at 230aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7 Hz, 3H), 1,67 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), was 7.08 (DD, J= 9 and 2 Hz, 1H), 7,52 (d, J= 2 Hz, 1H), to 7.84 (d, J= 9 Hz, 1H), accounted for 10.39 (array, 1H), 12,50-13,00 (array ush., 1H).

Example 12

6-Bromo-1H-indazol-3-amine

To 10 g of 4-bromo-2-perbenzoate 100 cm3ethanol is added to 7.3 cm3hydrazinoacetate. When food is refluxed at a temperature of 78 aboutWith in 12 hours. After that, the precipitation is filtered off on a glass Frit. After drying (90 PA; 45about(C) obtain 9.7 g of 6-bromo-1H-indazol-3-amine in the form of a solid white color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 5,45 (ush., 2H), 7,03 (DD, J= 9 and 2 Hz, 1H), 7,43 (d, J= 2 Hz, 1H), 7,65 (d, J= 9 Hz, 1H), 11,50 (array, 1H).

(2E)-N-(6-Bromo-1H-indazol-3-yl)-2-butanamide

To 2 g of 6-bromo-1H-indazol-3-amine obtained above in 30 cm3pyridine while cooling to a temperature of 3aboutTo add 1,07 cm3crotolaria. The environment is maintained at achieving again the temperature of the 19aboutWith in 12 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC) and the residue is treated with 20 cm3ethyl acetate and 20 cm3of distilled water. The aqueous phase is re-extracted with 20 cm3ethyl acetate. The organic phases are combined and then evaporated under these conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume) and collecting fractions 15 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45o (C) obtain 130 mg of N-(6-bromo-1H-indazol-3-yl)-2-butanamide (form E) solid beige color, melting at 232aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1,91 (DD, J= 7 and 1.5 Hz, 3H), 6,27 (DD, J= 15 and 1.5 Hz, 1H), 6.89 in (d kV, J=15 and 7 Hz, 1H), 7,20 (DD, J= 9 and 2 Hz, 1H), 7,68 (d, J= 2 Hz, 1H), 7,87 (d, J= 9 Hz, 1H), 10,54 (array, 1H), 12,80 (array ush., 1H).

Example 13

(2E)-N-(5-Methyl-1H-indazol-3-yl)-2-butanamide

To 560 mg of 5-methyl-1H-indazol-3-amine, obtained as described in European patent 909720, 30 cm3pyridine add 0,33 cm3crotolaria. The reaction medium is maintained at achieving again the temperature of the 19aboutWith in 12 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC) and the residue is treated with 25 cm3tetrahydrofuran (THF, 25 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is washed with 2 times 25 cm3of distilled water. Dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume) and collecting fractions of 20 cm3. Faction, the soda is containing the target product, combined and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) receive 50 mg of N-(5-methyl-1H-indazol-3-yl)-2-butanamide (form E) in a solid white color, melting at 218aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1,90 (l ush., J= 7 Hz, 3H), of 2.38 (s, 3H), and 6.25 (DD, J= 15 and 1.5 Hz, 1H), 6,86 (l kV, J= 15 and 7 Hz, 1H), 7,17 (DD, J= 9 and 2 Hz, 1H), 7,34 (d, J= 9 Hz, 1H), 7,56 (ush., 1H), 10,31 (array, 1H), to 12.52 (array, 1H).

Example 14

N-(6-Chloro-1H-indazol-3-yl)-2-propenamide

To 750 mg of 6-chloro-1H-indazol-3-amine in 10 cm3pyridine while cooling to a temperature of 3aboutTo add to 0.39 cm3propionitrile. The environment is maintained at achieving again the temperature of the 19aboutWith in 12 hours and the reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 40 cm3tetrahydrofuran (THF, 40 cm3ethyl acetate and 40 cm3of distilled water. The organic phase is washed with 40 cm3distilled water and 40 cm3saturated aqueous solution of sodium chloride. Dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter, the ETP 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume) and collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The resulting product is treated with 50 cm3diethyl ether, filtered off on a glass Frit and then washed with 2 times 10 cm3diethyl ether. Filtered off under vacuum and after drying (90 PA; 45about(C) obtain 440 mg of N-(6-chloro-1H-indazol-3-yl)-2-propenamide in a solid white color, melting at 210aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 5.66 (s, 2H), 7,42 (d, J= 9 Hz, 1H), 7,50 (d ush., J= 9 Hz, 1H), they were 8.22 (ush., 1H), 10,86 (array, 1H).

Example 15

(2E)-N-[6-(Trifluoromethyl)-1H-indazol-3-yl]-2-butanamide

To 500 mg of 6-trifluoromethyl-1H-indazol-3-amine, obtained as described in U.S. patent 3133081, 10 cm3pyridine while cooling to a temperature of 10aboutTo add to 0.23 cm3crotolaria. The environment is maintained at achieving again the temperature of the 19aboutC for 17 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC) and the residue is treated with 25 cm3tetrahydrofuran (THF, 25 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is washed through the th 25 cm 3of distilled water. The combined organic phases are dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume) and collecting fractions at 30 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 30 cm3di-isopropyl ether, then filtered off on a glass Frit. After drying (90 PA; 45about(C) obtain 41 mg of N-[6-(trifluoromethyl)-1H-indazol-3-yl]-2-butanamide (form E) in a solid white color, melting at 208aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1,91 (DD, J= 7 and 1.5 Hz, 3H), of 6.29 (DD, J= 15 and 1.5 Hz, 1H), 6,91 (l kV, J= 15 and 7 Hz, 1H), 7,35 (l ush., J= 9 Hz, 1H), 7,83 (ush., 1H), 8,11 (d, J= 9 Hz, 1H), 10,65 (array, 1H), 12,60-13,50 (array ush., 1H).

Example 16

Ethyl-4-[[6-(trifluoromethyl)-1H-indazol-3-yl]amino]-4-oxobutanoate

To 249 mg 6-(trifluoromethyl)-1H-indazol-3-amine, obtained as described in U.S. patent 3133081, 10 cm3pyridine while cooling to a temperature of 10aboutTo add to 0.23 cm3crotonyl lorida. The environment is maintained at achieving again the temperature of the 19aboutC for 17 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 25 cm3tetrahydrofuran (THF, 25 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is washed with 2 times 25 cm3of distilled water. The combined organic phases are dried over magnesium sulfate and filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 98:2 by volume) and collecting fractions at 30 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) obtain 210 mg of ethyl-4-[[6-(trifluoromethyl)-1H-indazol-3-yl]amino]-4-oxobutanoate in a solid white color, melting at 248aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 1.21 (t, J= 7 Hz, 3H), 2,60 is 2.80 (m, 4H), 4,10 (kV, J= 7 Hz, 2H), 7,35 (l ush, J= 9 Hz, 1H), 7,84 (ush., 1H), 8,02 (d, J= 9 Hz, 1H), 10,61 (array, 1H), 12,60-13,60 (array ush., 1H).

Example 17

(2E)-N-[5-(trifluoromethyl)-1H-indazol-3-yl]-2-butanamide

To 500 mg of 5-(t is iformity)-1H-indazol-3-amine, obtained according to the U.S. patent 3133081, 15 cm3pyridine add 0,24 cm3crotolaria. Stirred at a temperature of 19aboutWith in 12 hours and the reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 25 cm3tetrahydrofuran (THF, 25 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is again washed with 25 cm3of distilled water. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume) and collecting fractions of 25 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) obtain 63 mg of N-[5-(trifluoromethyl)-1H-indazol-3-yl]-2-butanamide (form E) in a solid white color, melting at 242aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1,91 (DD, J= 7 and 1.5 Hz, 3H), 6.30-in (DD, J= 15 and 1.5 Hz, 1H), 6,93 (l kV, J= 15 and 7 Hz, 1H), 7,60 (DD, J= 9 and 2 Hz, 1H), 7,66 (d, J= 9 Hz, 1H), 8,42 (ush., 1H), of 10.73 (array, 1H), 12,90-13,40 (the array is sh. 1H).

Example 18

N-[5-Chloro-1H-indazol-3-yl]-2-butanamide

To 500 mg of 5-chloro-1H-indazol-3-amine obtained according to European patent 90972, 25 cm3pyridine while cooling to a temperature of 5aboutTo add 0,31 cm3butyrylcholine. The environment is maintained at achieving again the temperature of the 19aboutC for 17 hours and the reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 25 cm3tetrahydrofuran (THF, 25 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume) and collecting fractions at 30 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) receive 100 mg of N-[5-chloro-1H-indazol-3-yl]-2-butanamide in a solid white color, melting at 216aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7.5 Hz, 2H), 7,35 (DD, J= 9 and 2 Hz, 1H), 7,49 (DD,J= 9 and 0.5 Hz, 1H), 7,86 (DD, J= 2 and 0.5 Hz, 1H), 10,41 (array, 1H), 12,82 (array, 1H).

Example 19

N-[4-Chloro-1H-indazol-3-yl]butanamide

To 1 g of 4-chloro-1H-indazol-3-amine, obtained as described in European patent 90972, 10 cm3pyridine while cooling to a temperature of 10aboutTo add to 0.23 cm3butyrylcholine. Stand upon reaching again the temperature of the 19aboutC for 17 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 25 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is washed with 2 times 25 cm3distilled water and 25 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 99:1 by volume) and collecting fractions at 30 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Thus receive 80 mg of N-[4-chloro-1H-indazol-3-yl]butanamide in a solid white color, melting at 198aboutC.

<> 1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7 Hz, 3H), of 1.66 (m, 2H), 2,35 (t ush., J= 7 Hz, 2H), 7,15 (l ush., J= 8 Hz, 1H), 7,34 (t, J= 8 Hz, 1H), 7,49 (d, J= 8 Hz, 1H), 9,80 (array, 1H).

Example 20

N-[6-(Trifluoromethyl)-1H-indazol-3-yl]butanamide

To 500 mg of 6-(trifluoromethyl)-1H-indazol-3-amine, obtained as described in U.S. patent 3133081, 5 cm3pyridine while cooling to a temperature of 10aboutTo add 0,26 cm3butyrylcholine. Stand upon reaching again the temperature of the 19aboutC for 19 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 15 cm3ethyl acetate and 15 cm3of distilled water. The organic phase is washed with 15 cm3distilled water and 15 cm3saturated aqueous solution of magnesium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume) and collecting fractions of 20 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After wyszukiwanie is (90 PA; 45about(C) obtain 49 mg of N-[6-(trifluoromethyl)-1H-indazol-3-yl]butanamide in a solid white color, melting at 200aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7.5 Hz, 2H), 7,34 (l ush., J= 9 Hz, 1H), 7,82 (ush., 1H), 8,04 (d, J= 9 Hz, 1H), 10,49 (array, 1H), 13,10 (array ush., 1H).

Example 21

6-Chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-amine

478 mg of sodium hydride in 50 cm3anhydrous DMF (dimethylformamide) add a solution of 2 g of 6-chloro-1H-indazol-3-amine in 20 cm3of dimethylformamide. Then cooled to a temperature of 3aboutWith and add 2,12 cm3[2-(trimethylsilyl)ethoxy]methyl chloride in 10 cm3of dimethylformamide. Withstand before reaching again the temperature of the 19aboutC for 45 minutes, then treated with 250 cm3ethyl acetate. Washed 3 times in 100 cm3distilled water and 100 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 40aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume) and collecting fra is of 100 cm 3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Receive 2 g of 6-chloro-1-[[(2-trimethylsilyl)ethoxy]methyl]-1H-indazol-3-amine in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: -0,09 (s, N), to 0.80 (t, J= 8 Hz, 2H), 3,48 (t, J= 8 Hz, 2H), 5,43 (s, 2H), 5,68 (C, ush., 2H), 7,01 (DD, J= 9 and 2 Hz, 1H), to 7.61 (d, J= 2 Hz, 1H), 7,74 (d, J= 9 Hz, 1H).

N-[6-Chloro-1-[(2-trimethylsilyloxy)methyl]-1H-indazol-3-yl]-propanamide

To 1 g of 6-chloro-1-[[(2-trimethylsilyl)ethoxy]methyl]-1H-indazol-3-amine described above, in 25 cm3dichloromethane and 0.57 cm3triethylamine add 0,33 cm3akriloilkhlorida. The reaction medium is stirred for 30 minutes, then evaporated under reduced pressure (2 kPa; 40aboutC). The residue is treated with 100 cm3ethyl acetate and washed with 2 times 50 cm3distilled water and 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 40aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume) and collecting fractions of 35 cm3. Faction is, containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) receive 160 mg of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]propanamide in a solid white color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: -0,08 (s, N), or 0.83 (t, J= 8 Hz, 2H), 3,54 (t, J= 8 Hz, 2H), of 5.68 (s, 2H), of 5.84 (DD, J= 10.5 and 2 Hz, 1H), 6.35mm (DD, J= 16.5 and 2 Hz, 1H), 6,60 (DD, J= 16.5 and 10.5 Hz, 1H), 7,18 (DD, J= 9 and 2 Hz, 1H), 7,88 (d, J= 2 Hz, 1H), 8,00 (d, J= 9 Hz, 1H), the 10.40 (array, 1H).

N-[6-Chloro-1H-indazol-3-yl]propanamide

To 160 mg of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]propanamide described above, in 10 cm3ethanol add 5 cm35 N. hydrochloric acid. The medium is heated at a temperature of 78aboutC for 30 minutes. Then held until it reaches again the temperature of the 19aboutWith and add 6 cm35 n sodium hydroxide solution. The reaction medium is evaporated under reduced pressure (2 kPa; 40aboutC) and the residue is treated with 50 cm3ethyl acetate, 25 cm3of tetrahydrofuran and 20 cm3of distilled water. The organic phase is washed with 50 cm3saturated aqueous solution of sodium chloride. After this dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 40aboutC). the STATCOM purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; 1.5 cm in diameter), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume) and collecting fractions by 7 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3dichloromethane, filtered off the insoluble portion on a glass Frit and washed with 2 times 5 cm3dichloromethane. After drying (90 PA; 45about(C) receiving 10 mg of N-[6-chloro-1H-indazol-3-yl]propanamide in a solid white color, melting at 205aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 5.82 (DD, J= 10.5 and 2 Hz, 1H), 6,34 (DD, J= 17 and 2 Hz, 1H), 6,60 (DD, J= 17 and 10.5 Hz, 1H), 7,10 (DD, J= 9 and 2 Hz, 1H), 7,54 (d, J= 2 Hz, 1H), 7,95 (d, J= 9 Hz, 1H), 10,78 (array ush., 1H), 12,86 (array ush., 1H).

Example 22

N-[5-(Trifluoromethyl)-1H-indazol-3-yl]butanamide

To 500 mg of 5-(trifluoromethyl)-1H-indazol-3-amine obtained according to the U.S. patent 3133081, 15 cm3pyridine while cooling to a temperature of 5aboutTo add 0,26 cm3butyrylcholine. The reaction medium is maintained at achieving again the temperature of the 19aboutWith in 12 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 15 cm3ethyl acetate and 15 cm3of distilled water. The organic phase from the shat over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 15 cm3dichloromethane, filtered and dried under reduced pressure (90 PA; 50aboutC)receiving 390 mg of N-[5-(trifluoromethyl)-1H-indazol-3-yl]butanamide in a solid off-white color, melting at 230aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,43 (t, J= 7 Hz, 2H), 7,60 (DD, J= 9 and 1.5 Hz, 1H), 7,65 (t, J= 9 Hz, 1H), 8.34 per (ush., 1H), or 10.60 (ush., 1H), 13,06 (ush., 1H).

Example 23

N-[5-Nitro-1H-indazol-3-yl]butanamide

To 1 g of 5-nitro-1H-indazol-3-amine, obtained as described in the patent of the USSR 742430, 25 cm3pyridine while cooling to a temperature of 5aboutWith the add of 0.58 cm3butyrylcholine. The reaction medium is maintained at achieving again the temperature of the 19aboutWith in 12 hours. Filter available insoluble part, then the filtrate is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 15 cm3ethyl acetate and 15 cm3of distilled water. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under pressure arg is 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume) and collecting fractions of 20 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) obtain 480 mg of N-[5-nitro-1H-indazol-3-yl]butanamide in a solid white color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), of 1.70 (m, 2H), 2,46 (t, J= 7 Hz, 2H), 7,63 (d, J= 9 Hz, 1H), 8,18 (DD, J= 9 and 2 Hz, 1H), 9,05 (t, J= 2 Hz, 1H), 10,77 (array, 1H), 13,00-13,70 (array ush., 1H).

Example 24

N-[6-Bromo-1H-indazol-3-yl]butanamide

To 500 mg of 6-bromo-1H-indazol-3-amine described above in example 12, in 15 cm3pyridine while cooling to a temperature of 5aboutTo add to 0.24 cm3butyrylcholine. The reaction medium is maintained at achieving again the temperature of the 19aboutWith over 50 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 15 cm3ethyl acetate and 15 cm3of distilled water. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 15 cm3dichloromethane, filtered, receiving, after drying under reduced pressure (90 PA; 0 aboutC), 356 mg of N-[6-bromo-1H-indazol-3-yl]butanamide in a solid off-white color, melting at 202aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J=7.5 Hz, 3H), 1,67 (m, 2H), 2,39 (t ush., J= 7 Hz, 2H), 7,20 (l ush., J= 9 Hz, 1H), 7,68 (ush., 1H), 7,78 (l ush., J= 9 Hz, 1H), the 10.40 (array, 1H), was 12.75 (array, 1H).

Example 25

N-[6-Chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide

To 606 mg of 60 %sodium hydride in 20 cm3of dimethylformamide, add 3 g of N-(6-chloro-1H-indazol-3-yl)butanamide described above in example 11, in the form of a solution in 40 cm3of dimethylformamide. After cooling to a temperature of 5aboutTo add 2,68 cm3[[2-(trimethylsilyl)ethoxy]methyl]chloride in 10 cm3of dimethylformamide. Withstand before reaching again the temperature of the 21aboutC and stirred for 2 hours. Reaction medium was then evaporated under reduced pressure (2 kPa; 45aboutC). The residue is treated with 200 cm3ethyl acetate and 100 cm3of distilled water. The organic phase is again washed with 2 times 100 cm3distilled water and 100 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). OS is atok purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume) and collecting fractions of 100 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) receiving 3 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), or 0.83 (t ush., J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2.40 a (t, J= 7.5 Hz, 2H), 3,53 (t, J= 8 Hz, 2H), to 5.66 (s, 2H), 7,16 (DD, J= 9 and 2 Hz, 1H), 7,86 (d, J= 2 Hz, 1H), 7,88 (d, J= 9 Hz, 1H), 10,53 (array, 1H).

N-[6-(3-Pyridinyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1.5 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 40 cm3dioxane is added 900 mg diethyl-3-pyridylamine, 1.86 g of cesium fluoride, an 18.4 mg of palladium acetate and finally, 48 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)diphenyl. Then heated at a temperature of about 100aboutC for 17 hours, and then filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 75 cm3ethyl acetate and 50 cm3of distilled water. The organic phase is again washed with 50 cm3distilled water and 50 cm3rich is on an aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure under these conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume) and collecting fractions of 25 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50aboutC) get 900 mg of N-[6-(3-pyridinyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), from 0.84 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), of 1.70 (m, 2H), 2,43 (t, J= 7.5 Hz, 2H)and 3.59 (t, J= 8 Hz, 2H), USD 5.76 (s, 2H), 7,52 (DD, J= 9 and 2 Hz, 1H), 7,55 (DD ush., J= 8.5 and 4.5 Hz, 1H), of 7.97 (d, J= 9 Hz, 1H), 8,09 (ush., 1H), to 8.20 (DDD, J= 8,5 - 2.5 and 2 Hz, 1H), 8,63 (DD, J= 4.5 and 2 Hz, 1H), 9,02 (l ush., J= 2.5 Hz, 1H), 10,51 (array, 1H).

N-[6-(3-Pyridinyl)-1H-indazol-3-yl]butanamide

To 900 mg of N-[6-(3-pyridinyl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 20 cm3tetrahydrofuran (THF) add 13,3 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 21 hours. Then the pre heated remaut and add 100 cm 3ethyl acetate. Washed with 50 cm3saturated aqueous sodium hydrogen carbonate solution, then with 2 times 50 cm3distilled water and 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira with ethyl acetate and collecting fractions of 25 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) obtain 380 mg of N-[6-(3-pyridinyl)-1H-indazol-3-yl]butanamide in the form of a white product melting at 205aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), of 1.70 (m, 2H), 2,41 (t, J= 7 Hz, 2H), 7,42 (DD, J= 9 and 1.5 Hz, 1H), 7,53 (DDD, J= 8 and 5 and 0.5 Hz, 1H), 7,73 (ush., 1H), 7,92 (l ush., J= 9 Hz, 1H), 8,18 (DDD, J= 8 - 2 and 1.5 Hz, 1H), to 8.62 (DD, J= 5 and 2 Hz, 1H), 8,98 (l ush., J= 1.5 Hz, 1H), 10,37 (array, 1H), 12,80 (array, 1H).

Example 26

4-Iodine-1H-indazol-3-amine

To 2 g of 2-fluoro-6-iodobenzonitrile 25 cm3ethanol add 1.2 cm3hydrazinoacetate. Then the reaction medium is refluxed at a temperature of 78aboutaboutWith, then add 20 cm3distilled water to precipitate the product. The insoluble part is filtered off on a glass filter, then washed with 20 cm3distilled water, then treated with 20 cm3dichloromethane. The organic phase is then dried over magnesium sulfate and evaporated under reduced pressure (2 kPa; 45aboutC). After drying (90 PA; 50about(C) gain of 1.65 g of 4-iodine-1H-indazol-3-amine in the form of a solid yellow color, melting at 157aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 5.05 (ush., 2H), 6,95 (DD, J= 7.5 and 8.5 Hz, 1H), 7,30 (DD, J= 8.5 and 1 Hz, 1H), 7,37 (l ush., J= 7.5 Hz, 1H), 11,80 (array, 1H).

N-[4-Iodine-1H-indazol-3-yl]butanamide

To 500 mg of 4-iodine-1H-indazol-3-amine described above, in 15 cm3pyridine while cooling to a temperature of 5aboutTo add to 0.20 cm3butyrylcholine. The reaction medium is maintained at achieving again the temperature of the 19aboutWith over 50 hours. The reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 15 cm3ethyl acetate, 15 cm3of tetrahydrofuran and 15 cm3of distilled water. The organic phase is dried over magnesium sulfate, and then filtered through glass policyfilter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 15 cm3dichloromethane and filtered. The insoluble part is treated using a 10 cm3methanol, the insoluble part is filtered off and the filtrate is evaporated under reduced pressure, obtaining, after drying (90 PA; 50aboutC), 70 mg of N-[4-iodine-1H-indazol-3-yl]butanamide in the form of a solid substance of indeterminate color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,39 (t ush., J= 7 Hz, 2H), to 7.09 (t, J= 8 Hz, 1H), 7,54 (d, J= 8 Hz, 1H), 7,58 (l ush., J= 8 Hz, 1H), 9,68 (ush., 1H), 13,08 (array, 1H).

Example 27

N-[6-Phenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide

To 1.5 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]1H-indazol-3-yl]butanamide described above in example 25, in 30 cm3dioxane add 497 mg of phenylboronic acid, 1.24 g of cesium fluoride, 12,35 mg of palladium acetate and finally, 48 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 100aboutC for 18 hours, then filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is washed with 50 cm3of tetrahydrofuran and 50 cm3of distilled water. Treated with 75 cm3ethyl acetate and 50 cm3of distilled water. The organic phase is dried over su is hatom magnesium, filtered through a porous glass filter, and then evaporated under reduced pressure under these conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 75:25 by volume) and collecting fractions of 25 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) receive 1 g of N-[6-phenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), from 0.84 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7 Hz, 2H)and 3.59 (t, J= 8 Hz, 2H), 5,74 (s, 2H), 7,42 (t ush., J= 7.5 Hz, 1H), 7,47 (DD, J= 9 and 1.5 Hz, 1H), 7,53 (t ush., J= 7.5 Hz, 2H), 7,79 (l ush., J= 7.5 Hz, 2H), to 7.93 (d, J= 9 Hz, 1H), of 7.96 (ush., 1H), 10,48 (array, 1H).

N-[6-Phenyl-1H-indazol-3-yl]butanamide

To 900 mg of N-[6-phenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) add 14,65 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 16 hours. Then the heat stops and add 75 cm3ethyl acetate. Washed with 75 cm3saturated vodno the solution of sodium bicarbonate, then 2 times in 75 cm3distilled water and 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with ethyl acetate and collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3ethyl acetate, then filtered on a glass Frit, washed with 2 times 5 cm3ethyl acetate and 20 cm3diisopropyl ether. After drying (90 PA; 50about(C) obtain 420 mg of N-[6-phenyl-1H-indazol-3-yl]butanamide in the form of a white product melting at 220aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,99 (t ush., J= 7 Hz, 3H), of 1.70 (m, 2H), 2,41 (t, J= 7 Hz, 2H), 7,37 (DD, J= 9 and 1.5 Hz, 1H), 7,40 (t ush., J= 7.5 Hz, 1H), 7,51 (t ush., J= 7.5 Hz, 2H), 7,63 (ush., 1H), 7,74 (l ush., J= 7.5 Hz, 2H), 7,98 (d, J= 9 Hz, 1H), 10,34 (array, 1H), 12,70(array, 1H).

Example 28

N-[6-Bromo-5,7-dinitro-1H-indazol-3-yl]butanamide

To 500 mg of N-[6-bromo-1H-indazol-3-yl]butanamide described above in example 24, 20 cm3acetone the Rila, when cooled to a temperature of 3aboutWith add at once 470 mg detroitmetroairport. Stand upon reaching again the temperature of the 19aboutC for 14 hours. In the reaction medium was added 15 cm3ethyl acetate and 15 cm3of distilled water. Wednesday then evaporated under reduced pressure (2 kPa; 40aboutC) and the residue is treated with 20 cm3dichloromethane. The insoluble part is filtered off and washed it with 20 cm3diisopropyl ether. After drying (90 PA; 45about(C) receive 200 mg of N-[6-bromo-5,7-dinitro-1H-indazol-3-yl]butanamide in the form of solids ochre color, melting at 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,45 (t, J= 7.5 Hz, 2H), 9,05 (s, 1H), 11,06 (array, 1H), 14,04 (array, 1H).

Example 29

N-[6-Bromo-7-nitro-1H-indazol-3-yl]butanamide

To 500 mg of N-[6-bromo-1H-indazol-3-yl]butanamide described above in example 24, 25 cm3acetonitrile, while cooling to a temperature of 3aboutWith add at a time 235 mg detroitmetroairport. Maintained at a temperature of 3aboutC for 1 hour, then upon reaching again the temperature of the 19aboutC for 14 hours. In the reaction medium was added 15 cm3ethyl acetate and 15 cm3of distilled water. Wednesday then evaporated the ri reduced pressure (2 kPa; 40aboutC) and the residue is treated with 20 cm3dichloromethane. The insoluble part is filtered off and washed it with 20 cm3diisopropyl ether. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira a mixture of ethyl acetate and cyclohexane (in the ratio of 30:70 by volume) and collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) receive 30 mg of N-[6-bromo-7-nitro-1H-indazol-3-yl]butanamide in the form of a white product melting at 248aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,43 (t, J= 7.5 Hz, 2H), 7,54 (d ush., J= 9 Hz, 1H), 8,13 (d, J= 9 Hz, 1H), is 10.68 (array, 1H), 13,44 (array ush., 1H).

Example 30

N-[6-Bromo-5-nitro-1H-indazol-3-yl]butanamide

During purification by chromatography according to example 29 under the pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira a mixture of ethyl acetate and cyclohexane (in the ratio of 30:70 by volume), collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) receiving 10 mg of N-[6-b is ω-5-nitro-1H-indazol-3-yl]butanamide in the form of a white product melting at 259aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm as 0.96 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,43 (t, J= 7.5 Hz, 2H), 7,95 (s, 1H), 8,81 (s, 1H), 10,80 (array, 1H), 12,70-13,70 (array ush., 1H).

Example 31

N-[6-(Furan-3-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 25, in 30 cm3dioxane add 457 mg furan-3-Bronevoy acid, 1.24 g of cesium fluoride, 13 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 100aboutC for 23 hours. Add another 457 mg furan-3-Bronevoy acid, 1.24 g of cesium fluoride, 13 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl and continue boiling under reflux for 7 hours. Then stand upon reaching again the temperature of the 19aboutC for 16 hours, then filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is washed with 50 cm3of tetrahydrofuran and 50 cm3of distilled water. Treated with 75 cm3ethyl acetate and 50 cm3of distilled water. The organic phase is dried over magnesium sulfate, filtered through a porous glass is iltr, then evaporated under reduced pressure under these conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume) and collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 130 mg of N-[6-(furan-3-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of an orange oil.

The mass spectrum obtained by electron impact ionization (EI)(70 eV): m/z = 399 M+; m/z = 282 C16H13N3O2+; m/z = 271 (C15H13N3O2+; m/z = 212 (C12H10N3O+; m/z = 73 C3H9Si+.

N-[6-(Furan-3-yl)-1H-indazol-3-yl]butanamide

To 120 mg of N-[6-(furan-3-yl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 5 cm3tetrahydrofuran (THF) add 1,95 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 17 hours. Then the heat stops and add 50 cm3ethyl acetate. Washed with 50 cm3saturated aqueous sodium hydrogen carbonate solution, then 50 cm3the saturated water is astora sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira a mixture of ethyl acetate and cyclohexane (in the ratio of 30:70 by volume) and collecting fractions 15 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3diisopropyl ether. Filtered off on a glass Frit, receiving, after drying (90 PA; 50aboutC), 35 mg of N-[6-(furan-3-yl)-1H-indazol-3-yl]butanamide in a solid white color, melting at 195aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 7,06 (ush., 1H), 7,34 (l ush., J= 9 Hz, 1H), 7,60 (ush., 1H), 7,70-a 7.85 (m, 2H), 8,27 (ush., 1H), 10,29 (array, 1H), br12.62 (array, 1H).

Example 32

N-[6-[4-(Phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 25, in 30 cm3dioxane add 930 mg 4-benzyloxyaniline acid, 1.24 g of cesium fluoride, 13 mg of palladium acetate and finally 31 m is 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 100aboutC for 5 hours. Then held until it reaches again the temperature of the 19aboutC, then filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is washed with 50 cm3of tetrahydrofuran and 50 cm3of distilled water. Treated with 150 cm3ethyl acetate, 50 cm3distilled water and 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure under these conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume) and collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 1.2 g of N-[6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of an orange oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), or 0.83 (t ush., J= 8 Hz, 2H), 0,99 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,42 (t ush., J= 7 Hz, 2H), 3,57 (t ush., J= 8 Hz, 2H), total of 5.21 (s, 2H), 5,73 (s, 2H), 7,16 (d, J= 8.5 Hz, 2H), 7,30-to 7.50 (m, 4H), 7,51 (l ush., J= 7.5 Hz, 2 Is), 7,73 (d, J= 8.5 Hz, 2H), a 7.85-to 7.95 (m, 2H), 10,46 (array, 1H).

N-[6-[4-(Phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

To 1.2 g of N-[6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) added 14 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 17 hours. Then the heat stops and add 75 cm3ethyl acetate. Washed with 50 cm3saturated aqueous sodium hydrogen carbonate solution, then 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume) and collecting fractions at 30 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated 2 times 2 cm3diisopropyl ether. Filtered off on a glass Frit, receiving, after drying (90 PA; 50aboutC), 220 mg of N-[6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butane is IDA in the form of a solid white color, melting at 220aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1.00 m (t ush., J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,41 (t, J= 7 Hz, 2H), 5,20 (s, 2H), 7,15 (d, J= 8.5 Hz, 2H), 7,30-to 7.50 (m, 3H), 7,33 (l ush., J= 9 Hz, 1H), 7,51 (l ush., J= 7.5 Hz, 2H), EUR 7.57 (ush., 1H), 7,68 (d, J= 8.5 Hz, 2H), 7,83 (d, J= 9 Hz, 1H), 10,31 (array, 1H), 12,64 (array, 1H).

Example 33

N-[6-(4-Hydroxyphenyl)-1H-indazol-3-yl]butanamide

To 200 mg of N-[6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide described above 7.5 cm3acetonitrile, add 0.15 cm3attributively, then 5 cm3tetrahydrofuran (THF) and the medium is heated at a temperature of 82aboutC for 2 hours. Add 0.15 cm3attributively and continue heating for 17 hours. Reaction medium was then evaporated to dryness under reduced pressure (2 kPa; 40aboutC). The residue is treated with 75 cm3ethyl acetate, then washed with 2 times 50 cm3saturated aqueous solution of sodium sulfate and with 50 cm3a saturated solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered, then evaporated under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 1.5 cm), elwira with ethyl acetate and collecting fractions at 30 cm3. The fractions containing relevo the product, combined and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is washed 3 times for 5 cm3diisopropyl ether. It is filtered off on a glass Frit and, after drying (90 PA; 40about(C)receive 100 mg of N-[6-(4-(hydroxyphenyl)-1H-indazol-3-yl]-butanamide in a solid white color, melting at 235aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7.5 Hz, 2H), to 6.88 (d, J= 8.5 Hz, 2H), 7,29 (l ush., J= 9 Hz, 1H), 7,51 (ush., 1H), 7,55 (d, J= 8.5 Hz, 2H), 7,80 (d, J= 9 Hz, 1H), 9,56 (ush., 1H), 12,29 (array, 1H).

Example 34

N-[6-Chloro-1H-indazol-3-yl]benzolamide

To 1 g of 6-chloro-1H-indazol-3-amine in 15 cm3pyridine while cooling to a temperature of 3aboutTo add to 0.69 cm3of benzoyl chloride. The environment is maintained at achieving again the temperature of the 19aboutWith in 12 hours and the reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 25 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is washed with 25 cm3distilled water and 25 cm3saturated aqueous solution of sodium chloride. Dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified chromium is ografia under pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 99:1 by volume) and collecting fractions 15 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) receive 990 mg of N-[6-chloro-1H-indazol-3-yl]benzolamide in a solid white color, melting at 188aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 7,13 (DD, J= 9 and 1.5 Hz, 1H), 7,50-of 7.70 (m, 3H), to 7.59 (ush., 1H), 7,82 (d, J= 9 Hz, 1H), 8,10 (l ush., J= 7.5 Hz, 2H), 10,88 (array, 1H), 12,95 (array, 1H).

Example 35

N-[6-(3,5-Differenl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 25, in 30 cm3dioxane add 645 mg of 3,4-diftorhinolonom acid, 1.24 g of cesium fluoride, 13 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 100aboutC for 17 hours. Then held until it reaches again the temperature of the 19aboutC, then filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 75 cm3ethyl acetate and 50 cm3of distilled water. The insoluble part is filtered off n the glass Frit. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure under these conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume) and collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 1.1 g of N-[6-(3,5-differenl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of an orange oil.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N)to 0.85 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), of 1.70 (m, 2H), 2,43 (t, J= 7.5 Hz, 2H)and 3.59 (t, J= 8 Hz, 2H), 5,77 (s, 2H), 7,28 (TT, J= 9 and 2 Hz, 1H), 7,55 (DD, J= 9 and 2 Hz, 1H), to 7.59 (m, 2H), 7,95 (d, J= 9 Hz, 1H), 8,12 (ush., 1H), 10,53 (array, 1H).

N-[6-(3,5-Differenl)-1H-indazol-3-yl]butanamide

To 1.1 g of N-[6-(3,5-differenl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) added 14 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 18 hours. Then the heat stops and add 100 cm3ethyl acetate. Washed with 2 times 50 cm3full of the CSOs aqueous solution of sodium bicarbonate, then using a 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume) and collecting fractions of 35 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated 2 times in 5 cm3diisopropyl ether. Filtered off on a glass Frit and dried (90 PA; 50aboutC)receiving 340 mg of N-[6-(3,5-differenl)-1H-indazol-3-yl]butanamide in a solid white color, melting at 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1.00 and (t, J= 7 Hz, 3H), of 1.70 (m, 2H), 2,42 (t, J= 7 Hz, 2H), 7,27 (TT, J= 9 and 2 Hz, 1H), 7,43 (DD, J= 9 and 2 Hz, 1H), 7,52 (m, 2H), 7,76 (ush., 1H), of 7.90 (d, J= 9 Hz, 1H), 10,37 (array, 1H), 12,83 (array ush., 1H).

Example 36

N-[6-(3-Thiophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 25, in 30 cm3dioxane add 522 mg 3-thienylboronic acids is, 1.24 g of cesium fluoride, 13 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 100aboutC for 2 hours. Added 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl and 13 mg of palladium acetate and refluxed for 17 hours. Then held until it reaches again the temperature of the 19aboutWith, and then filtered through a porous glass filter and add 75 cm3ethyl acetate and 50 cm3of distilled water. The insoluble part is filtered off on a glass Frit. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter, and then evaporated under reduced pressure under these conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume) and collecting fractions of 50 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 570 mg of N-[6-(3-thiophenyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N)to 0.85 (t, J= 8 Hz, 2H), 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7.5 Hz, 2H), to 3.58 t, J= 8 Hz, 2H), 5,72 (s, 2H), 7,55 (DD, J= 8.5 and 1.5 Hz, 1H), 7,71 (d, J= 2 Hz, 2H), 7,88 (d, J= 8.5 Hz, 1H), 8,00 (t, J= 2 Hz, 1H), 8,02 (ush., 1H), 10,45 (array, 1H).

N-[6-(3-Thiophenyl)-1H-indazol-3-yl]butanamide

To 570 mg of N-[6-(3-thiophenyl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 20 cm3tetrahydrofuran (THF) add 8.2 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 18 hours. Then the heat stops and add 75 cm3ethyl acetate. Washed with 2 times 50 cm3saturated aqueous sodium hydrogen carbonate solution, then with 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume) and collecting fractions of 20 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated 2 times in 5 cm3diisopropyl ether. Filtered off on a glass Frit and evaporated under reduced pressure (kPa; 40about(C)receiving, after drying (90 PA; 50aboutC), 260 mg of N-[6-(3-thiophenyl)-1H-indazol-3-yl]butanamide in a solid white color, melting at 198aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 7,45 (l ush., J= 9 Hz, 1H), 7,60 to 7.75 (m, 2H), 7,70 (ush., 1H), 7,82 (d, J= 9 Hz, 1H), 7,95 (DD, J= 3 and 1.5 Hz, 1H), 10,32 (array, 1H), 12,66 (array ush., 1H).

Example 37

N-[6-Chloro-1H-indazol-3-yl]-2-thiopheneacetic

To 1 g of 6-chloro-1H-indazol-3-amine in 15 cm3pyridine while cooling to a temperature of 3aboutTo add to 0.73 cm32-thiophenated. The environment is maintained at achieving again the temperature of the 19aboutWith over 21 hours and the reaction medium is evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 25 cm3ethyl acetate, 10 cm3of tetrahydrofuran and 25 cm3of distilled water. The organic phase is washed with 25 cm3distilled water and 25 cm3saturated aqueous solution of sodium chloride. Dried over magnesium sulfate, filtered through a porous glass filter, washed with 5 cm3of dimethylformamide, and then evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; d is amatr 4 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 99:1 by volume) and collecting fractions 15 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) obtain 210 mg of N-[6-chloro-1H-indazol-3-yl]-2-thiopheneacetic in a solid white color, melting at 210aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 3,99 (s, 2H), 6,95-7,10 (m, 2H), to 7.09 (DD, J= 9 and 2 Hz, 1H), 7,43 (DD, J= 5 and 1.5 Hz, 1H), 7,53 (d, J= 2 Hz, 1H), 7,82 (d, J= 9 Hz, 1H), 10,76 (array, 1H), 12,50-13,20 (array ush., 1H).

Example 38

N-[5-[[(3-Forfinal)sulfonyl]amino]-1H-indazol-3-yl]benzamide

N-[5-[[(3-Forfinal)sulfonyl]amino]-1H-indazol-3-yl]benzamide can be obtained from 0.45 g of N-(5-amino-1H-indazol-3-yl)benzamide, 10 cm3pyridine and 0.35 g of (3-forfinal)sulphonylchloride. Thus obtained 0.6 g of N-[5-[[(3-forfinal)-sulfonyl]amino]-1H-indazol-3-yl]benzamide in the form of a solid white color, melting at 225about(Analysis for C20H15FN4O3S: calculated, %: C: 58,53; N: 3,68; F: 4,63; N: 13,65;: Of 11.69; S: 7,81; found, %: C: 58,38; N: 3,42; N: 13.56MHz; S: 7,44).

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 7,10 (DD, J= 9 and 2 Hz, 1H), 7,39 (d, J= 9 Hz, 1H), 7,40-of 7.70 (m, 7H), 7,42 (ush., 1H), 8,07 (l ush., J= 7.5 Hz, 2H), 10,20 (array ush., 1H), of 10.72 (ush., 1H), 12,77 (ush., 1H).

N-(5-Amino-1H-indazol-3-yl)benzamide can be obtained from 0.6 g of N-(5-nitro-1H-indazol-3-yl)benzamide, 21 cm3ethanol and 4.2 g of sulfate ferrous iron, 6.6 cm3water and 5.1 cm332 %ammonium hydroxide solution. Thus obtained 0.4 g of N-(5-amino-1H-indazol-3-yl)benzamide in the form of a yellow powder, melting at 116aboutC.

N-(5-Nitro-1H-indazol-3-yl)benzamide can be obtained as follows: to a solution of 0.6 g of 5-nitro-1H-indazol-3-amine and 5 cm3pyridine, cooled to a temperature of 0aboutC, is added dropwise to 0.39 cm3of benzoyl chloride. Wednesday is brought to a temperature of about 20aboutC and maintained under stirring for 18 hours. After adding 20 cm3distilled water medium is extracted with 20 cm3and 10 cm3ethyl acetate. The combined organic phases, dried over magnesium sulfate, filtered and concentrated by evaporation under reduced pressure. Thus obtained residue is purified by chromatography on a column of silica gel using a mixture of dichloromethane and methanol (in a ratio of 99:1 by volume) as the eluting means. Thus obtain 0.9 g of N-(5-nitro-1H-indazol-3-yl)benzamide in the form of a solid orange color, melting at 231aboutC.

Example 39

N-[6-(2-Phenylethyl)-1-[[2-(trim Telcell)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To a solution of 0.8 cm3styrene 35 cm3dioxane syringe add 27,2 cm39-borabicyclo[3,3,1]nonane and heated at a temperature of 75aboutC for 1 hour. To the cooled solution was added 5.5 cm35 n sodium hydroxide solution, and then 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to example 25, 1.2 g of cesium fluoride, 32,2 mg 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl, 12,3 mg of palladium acetate and refluxed in techine 3 hours. After cooling, add 50 cm3water and 75 cm3ethyl acetate; the organic phase is decanted, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 40aboutC)receiving 4.5 g of crude product, which chromatographic under pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 75:25 by volume). The fractions containing the desired product are pooled and then evaporated under reduced pressure (2 kPa; 40aboutC)receiving 1.4 g of N-[6-(2-phenylethyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,06 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 3,00 (m, 4H), 3,53 (t, J= 8gts, 2H), 5,62 (s, 2H),? 7.04 baby mortality (l ush., J= 8.5 Hz, 1H), 7,15-7,40 (m, 5H), 7,50 (ush., 1H), 7,74 (d, J= 8.5 Hz, 1H), 10,38 (array, 1H).

Mass spectrum (EI): m/z = 437 M+;

m/z = 320 [M-OCH2CH2Si(CH3)3]+;

m/z = 309 [M-C6H12OSi]+.

N-[6-(2-Phenylethyl)-1H-indazol-3-yl]butanamide

To a solution of 1.4 g of N-[6-(2-phenylethyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 40 cm3tetrahydrofuran (THF) add 19,2 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours. To the reaction medium, add 100 cm3ethyl acetate and the organic phase is washed successively with 100 cm3a saturated solution of sodium bicarbonate, 100 cm3water and 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC)receiving 1.4 g of crude product as orange oil, which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 30:70 by volume). The fraction containing the target product, concentrated to dryness, obtaining of 0.43 g of yellow oil, from which, after powdering 20 cm3isopropylalcohol ether and filtering off, obtain 0.34 g of a solid substance of white color 70 %purity. After purification by high-performance liquid chromatography with mass spectrometry obtain 0.11 g of product, which proscout 10 cm3diisopropyl ether, filtered and washed with 5 cm3diisopropyl ether; the product is dried under reduced pressure (90 PA; 40aboutC)receiving 0.10 g of N-[6-(2-phenylethyl)-1H-indazol-3-yl]butanamide in a solid white color, melting at 175aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), of 2.38 (t, J= 7 Hz, 2H), 2,99 (m, 4H), 6,97 (l ush., J= 9 Hz, 1H), 7,15-to 7.35 (m, 5H), 7,20 (ush., 1H), to 7.77 (d, J= 9 Hz, 1H), 10,22 (ush., 1H), to 12.44 (ush., 1H).

Example 40

6,7-Debtor-1H-indazol-3-amine

To 0,46 cm32,3,4-tripersonal 10 cm3absolute ethanol add 0,32 cm3hydrazinoacetate. The medium is heated at a temperature of 75aboutC for 17 hours, then add 10 cm3ethyl acetate, 5 cm3of tetrahydrofuran and 5 cm3of distilled water. The organic phase is decanted and washed again with 10 cm3distilled water, then 10 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced giving the situation (2 kPa; 50aboutC). The resulting residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 1.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled and then evaporated under reduced pressure (2 kPa; 40aboutC). After drying (90 PA; 40about(C) receive 100 mg of 6,7-debtor-1H-indazol-3-amine in the form of a solid white color, melting at 183aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 5,57 (array, 2H), 6,93 (m, 1H), 7,52 (DDD, J= 8,5 - 4.5 and 1 Hz, 1H), 12,01 (array, 1H).

N-(6,7-Debtor-1H-indazol-3-yl)butanamide

To 1 g of 6,7-debtor-1H-indazol-3-amine described above, in 15 cm3pyridine, after cooling to a temperature of 3aboutTo add to 0.61 cm3butyrylcholine, then incubated at achieving again at room temperature for 76 hours. Reaction medium was concentrated under reduced pressure (2 kPa; 40aboutC) and the residue is treated with 25 cm3ethyl acetate and 25 cm3water. The organic phase is washed with 25 cm3distilled water, then 25 cm3saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, filtration and concentration under reduced pressure (2 kPa; 40about(C) received the initial residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 98:2 by volume). The fractions containing the desired product are pooled and then evaporated under reduced pressure (2 kPa; 40aboutC). After drying (90 PA; 40about(C) receive 596 mg of N-(6,7-debtor-1H-indazol-3-yl)butanamide in a solid white color, melting at 191aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 7,10 (m, 1H), 7,63 (DD ush., J= 9 and 4.5 Hz, 1H), 10,47 (array ush., 1H), 13,35 (array ush., 1H).

Example 41

N-[6-(4-Methoxyphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 25, in 30 cm3dioxane is added 900 mg 4-methoxyphenylacetic acid, 1.24 g of cesium fluoride, 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 100aboutWith over 20 hours and maintained at achieving again the temperature of the 19aboutC for 72 hours, after which the reaction medium is filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 50 cm3ethyl acetate and 50 cm3of distilled water. The organic phase is again about the see through 50 cm 3distilled water and 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered, then evaporated under reduced pressure under these conditions. The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) receive 1 g of N-[6-(4-methoxyphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,41 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), 3,83 (s, 3H), 5,72 (ush., 2H), 7,08 (l ush., J= 8.5 Hz, 2H), 7,42 (l ush., J= 8.5 Hz, 1H), 7,72 (d, J= 8.5 Hz, 2H), a 7.85-to 7.95 (m, 2H), 10,45 (array, 1H).

Mass spectrum (EI): m/z = 437 M+;

m/z = 320 [M-OCH2CH2Si(CH3)3]+;

m/z = 309 [M-C6H12OSi]+.

N-[6-(4-Methoxyphenyl)-1H-indazol-3-yl]butanamide

To 1 g of N-[6-(4-methoxyphenyl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) add 13,6 cm3tetrabutylammonium in the form of a 1 M solution of tetrahydro the uranium, then the reaction medium is heated at a temperature of 66aboutC for 19 hours. After that, the heating stops and add 75 cm3ethyl acetate. Washed with 2 times 50 cm3saturated aqueous sodium hydrogen carbonate solution, then with 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of ethyl acetate and cyclohexane (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3diisopropyl ether, filtered off and washed with 2 times 5 cm3diisopropyl ether, and then 2 times in 5 cm3ethyl acetate; after drying (90 PA; 50about(C) receive 500 mg of N-[6-(4-methoxyphenyl)-1H-indazol-3-yl]butanamide in the form of a white product melting at 210aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,41 (t, J= 7 Hz, 2H), 3,83 (s, 3H), 7,06 (d m, J= 8.5 Hz, 2H), 7,33 (DD, J= 9 and 1.5 Hz, 1H), 7,56 (ush., 1H), 7,78 (d m, J= 8.5 Hz, 2H), 7,83 (d, J= 9 Hz, 1H), 10,31 (array, 1H), br12.62 (array, 1H).

Example 42

N-[6-[4-(Methylthio)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 25, in 30 cm3dioxane add 0,81 g 86 %4-methyldiphenylamine acid, 1.24 g of cesium fluoride, 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 100aboutWith over 20 hours and maintained at achieving again at room temperature for 72 hours, after which the reaction medium is filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 50aboutC). Processing and purification carried out by analogy with the above example 41; thus receive of 0.60 g of N-[6-(4-methylthiophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,41 (t, J= 7 Hz, 2H), by 2.55 (s, 3H), of 3.57 (t, J= 8 Hz, 2H), 5,73 (s, 2H), 7,40 (l ush., J= 8.5 Hz, 2H), 7,45 (DD, J= 8.5 and 1.5 Hz, 1H), of 7.75 (d, J= 8.5 Hz, 2H), to $ 7.91 (d, J= 8.5 Hz, 1H), 7,94 (s, 1H), 10,47 (array, 1H).

Mass spectrum (EI): m/z = 455 M+;

m/z = 338 [M-OCH2CH2Si(CH3)3]+;

m/z = 327 [M-C6H12OSi]+.

N-[6-(4-Methylthiophenyl)-1H-indazol-3-yl]butanamide

To 600 mg of N-[6-[4(methylthio)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide, as described above, in 30 cm3tetrahydrofuran (THF) add 7.9 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 18 hours, then heated to stop and add 75 cm3ethyl acetate. Washed with 2 times 50 cm3saturated aqueous sodium hydrogen carbonate solution, then with 50 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of ethyl acetate and cyclohexane (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3diisopropyl ether, filtered off and washed with 2 times 5 cm3diisopropyl ether, then 2 times 3 cm3ethyl acetate; after drying (90 PA; 50about(C) obtain 320 mg of N-[6-[4-(methylthio)phenyl]-1H-indazol-3-yl]butanamide in the form of a white product melting at 225aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2.40 a (t, J= Hz, 2N), of 2.54 (s, 3H), of 7.36 (DD, J= 9 and 1.5 Hz, 1H), 7,39 (d, J= 8.5 Hz, 2H), 7.62mm (ush., 1H), of 7.70 (d, J= 8.5 Hz, 2H), 7,86 (d, J= 9 Hz, 1H), 10,33 (array, 1H), 12,69 (array, 1H).

Example 43

N-[6-[4-(Triptoreline)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 25, in 30 cm3dioxane add 840 mg of 4-triftormetilfullerenov acid, 1.24 g of cesium fluoride, 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 102aboutWith over 20 hours, and then held until it reaches again the room temperature and the reaction medium is diluted with 75 cm3ethyl acetate, filtered through a porous glass filter with telicom and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). Processing and purification carried out by analogy with the above example 41. Thus get 1 g of N-[6-[4-(triptoreline)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,42 (t, J= 7 Hz, 2H), only 3.57 (t, J= 8 Hz, 2H), 5,74 (ush., 2H), 7,46 (DD, J= 8.5 and 1.5 Hz, 1H), 7,50 (d ush., J= 8.5 Hz, 2H), of 7.90 (d, J= 8.5 Hz, 2H), 7,94 (d, J= 8.5 Hz, 1H), 7,99 (ush., 1H), 10,49 (array, 1H).

<> Mass spectrum (EI): m/z = 493 M+;

m/z = 376 [M-OCH2CH2Si(CH3)3]+;

m/z = 365 [M-C6H12OSi]+.

N-[6-(4-Trifloromethyl)-1H-indazol-3-yl]butanamide

To 1 g of N-[6-[4-(triptoreline)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) add 12,1 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 18 hours. Then the heat stops and add 75 cm3ethyl acetate. Washed with 2 times 50 cm3saturated aqueous sodium hydrogen carbonate solution, then with 50 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of ethyl acetate and cyclohexane (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3diisopropyl ether, filtered off on a glass Frit and washed sequentially with 10 cm 3diisopropyl ether, then 2 times 2 cm3ethyl acetate. After drying (90 PA; 50about(C) obtain 520 mg of N-[6-[4-(triptoreline)phenyl]-1H-indazol-3-yl]butanamide in the form of a white product melting at 234aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,41 (t, J= 7 Hz, 2H), 7,38 (d ush., J= 9 Hz, 1H), 7,52 (d, J= 8.5 Hz, 2H), to 7.67 (ush., 1H), 7,86 (d, J= 8.5 Hz, 2H), 7,89 (d, J= 9 Hz, 1H), 10,36 (array, 1H), was 12.75 (array, 1H).

Example 44

N-[6-(2-Propenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to example 25, in 30 cm3dioxane successively added 1.24 g of cesium fluoride, 0,77 cm32-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 31,5 mg 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl, 13.5 mg of palladium acetate and refluxed for 18 hours. The reaction medium is filtered, treated with 2 times 50 cm3ethyl acetate and the organic phase is washed successively with 50 cm3water and 50 cm3a saturated solution of sodium chloride. After decanting, the organic phase, drying over sodium sulfate, filtering and concentrating to dryness under reduced pressure (2 kPa; 50about(C) obtain 1.3 g of a brown oil, which which purify by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume). After concentration and drying (90 PA; 45aboutC) get to 0.72 g of N-[6-(2-propenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil 75 %purity.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), of 0.82 (t, J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 3.45 points-of 3.60 (m, 4H), of 5.05-5,20 (m, 2H), 5,62 (s, 2H), 6,02 (m, 1H), 6,98 (l ush., J= 8.5 Hz, 1H), 7,45 (ush., 1H), of 7.75 (d, J= 8.5 Hz, 1H), 10,38 (array, 1H).

Mass spectrum (EI): m/z = 373 M+;

m/z = 256 [M-OCH2CH2Si(CH3)3]+;

m/z = 245 [M-C6H12OSi]+.

N-[6-(1-Propenyl)-1H-indazol-3-yl]butanamide

To a solution 0,70 g of N-[6-(1-propenyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide 25 cm3tetrahydrofuran (THF) add 11.2 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours. In the reaction medium was added 75 cm3ethyl acetate and the organic phase is washed successively with 2 times 50 cm3a saturated solution of sodium bicarbonate and 2 times 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50about), getting 0,70 g solid brown color. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). After concentration of the fractions gain of 0.30 g of a mixture containing 50 % of the target product. By the last high-performance liquid chromatography (column Hypurity; C18, 5 μm; length 100 mm, diameter 30 mm; eluting agent: a mixture of methanol, acetonitrile and water (in the ratio of 38:38:24 by volume)containing 0.05 % triperoxonane acid; flow 20 cm3/min) and concentration to dryness of fractions, treatment with 5 cm3ethyl acetate, filtration and drying (90 PA; 45about(C) obtain 12 mg of N-[6-(1-propenyl)-1H-indazol-3-yl]butanamide in the form of white crystals, melting at 195aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t ush., J= 7.5 Hz, 3H), of 1.66 (m, 2H), 1,89 (l ush., J= 6 Hz, 3H), is 2.37 (t, J= 7 Hz, 2H), 6,38 (m, 1H), 6,55 (l ush., J= 16 Hz, 1H), 7,17 (l ush., J= 8.5 Hz, 1H), 7,29 (ush., 1H), 7,69 (d, J= 9 Hz, 1H), 10,24 (array, 1H), to 12.52 (array, 1H).

Example 45

N-[6-Chloro-1H-indazol-3-yl]-2-pyridinecarboxamide

To 1 g of 6-chloro-1H-indazol-3-amine in 15 cm3pyridine type 4.2 cm3diisopropylethylamine. The reaction medium is cooled to a temperature of 8 With and add 1,08 g pikolinoilhydrazones and incubated at achieving again at room temperature for 18 hours. Reaction medium was concentrated to dryness under reduced pressure (2 kPa; 40aboutC), then the residue is treated with 25 cm3ethyl acetate and 25 cm3of distilled water. The organic phase is washed with 25 cm3water, then 25 cm3saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, filtration and concentration under reduced pressure (2 kPa; 40about(C) the residue purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 99:1 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC) and the residue is treated 2 x 15 cm3diisopropyl ether. After filtration over a glass Frit and dried under reduced pressure (90 PA; 50about(C) receive 572 mg of N-[6-chloro-1H-indazol-3-yl]-2-pyridinecarboxamide in a solid white color, melting at 177aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 7,14 (DD, J= 9 and 2 Hz, 1H), 7,60 (d, J= 2 Hz, 1H), 7,73 (DDD, J= 6,5 - 5 and 1.5 Hz, 1H), 7,95 (d, J= 9 Hz, 1H), 8,12 (t DD, J= 7.5 and 2 Hz, 1H), 8,21 (l ush., J= 7.5 Hz, 1H), 8,79 (l ush., J= 5 Hz, 1H), 10,50-11,40 (array ush., 1H), 12,30-13,40 (array t ush., 1H).

Example 46

N-[6-(4-Forfinal)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 25, in 30 cm3dioxane add 840 mg of 4-ftorhinolonovy acid, 1.24 g of cesium fluoride, 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 102aboutWith over 22 hours, and then held until it reaches again the room temperature. The reaction medium is treated with 75 cm3ethyl acetate, filtered through a porous glass filter with telicom and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). Processing and purification carried out by analogy with example 41. Thus obtain 580 mg of N-[6-(4-forfinal)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,41 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), 5,73 (s, 2H), 7,35 (t, J= 9 Hz, 2H), 7,44 (DD ush., J= 9 and 1.5 Hz, 1H), 7,82 (DD, J= 9 and 5.5 Hz, 2H), 7,92 (d, J= 9 Hz, 1H), 7,94 (ush., 1H), 10,48 (array, 1H).

Mass spectrum (EI): m/z = 427 M+;

m/z = 310 [M-OCH2CH2Si(CH3)3]+;

m/z= 299 [M-C 6H12OSi]+.

N-[6-(4-Forfinal)-1H-indazol-3-yl]butanamide

To 580 mg of N-[6-(4-forfinal)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) add 8,1 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and the reaction medium is heated at a temperature of 66aboutWith over 22 hours. Then the heat stops and add 75 cm3ethyl acetate, washed with 50 cm3saturated aqueous sodium hydrogen carbonate solution, then 50 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio of 40:60 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3diisopropyl ether, filtered and washed sequentially with 5 cm3diisopropyl ether and 2 times 3 cm3ethyl acetate; after drying (90 PA; 50about(C) receive 250 mg of N-[6-(4-forfinal)-1H-indazol-3-yl]butanamide the form of a white product melting at 232aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,39 (t, J= 7 Hz, 2H), 7,30 (d, J= 9 Hz, 1H), 7,32 (t, J= 9 Hz, 2H), to 7.61 (ush., 1H), 7,78 (DD, J= 9 and 6 Hz, 2H), 7,87 (d, J= 9 Hz, 1H), 10,33 (array, 1H), 12,70 (array, 1H).

Example 47

N-[6-[4-(1,1-Dimethylethyl))phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 25, in 30 cm3dioxane add 840 mg of 4-tert-butylaniline acid, 1.24 g of cesium fluoride, 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 102aboutC for 21 hours, then held until it reaches again the room temperature and the reaction medium is diluted with 75 cm3ethyl acetate, filtered through a porous glass filter with telicom and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). Processing and purification carried out by analogy with example 41. Thus obtain 1.13 g of N-[6-[4-(1,1-dimethylethyl)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), or 0.83 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), of 1.35 (s, N), by 1.68 (m, 2H), 2,41 (t, J= 7 Hz, 2H), only 3.57 (t, J= 8 Hz, 2H),5,72 (ush., 2H), 7,44 (l ush., J= 9 Hz, 1H), 7,53 (l ush., J= 8 Hz, 2H), 7,70 (l ush., J= 8 Hz, 2H), 7,89 (d, J= 9 Hz, 1H), to $ 7.91 (ush., 1H), 10,46 (array, 1H).

Mass spectrum (EI): m/z = 465 M+;

m/z = 348 [M-OCH2CH2Si(CH3)3]+;

m/z = 337 [M-C6H12OSi]+.

N-[6-[4-(1,1-Dimethylethyl)phenyl]-1H-indazol-3-yl]butanamide

To 1.13 g of N-[6-[4-(1,1-dimethylethyl)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) add 14.6 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 22 hours, then heating stopped and add 75 cm3ethyl acetate, the organic phase is washed with 75 cm3saturated aqueous sodium hydrogen carbonate solution, then with 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3diisopropyl the new ether, filtered off on a glass Frit and washed sequentially with 10 cm3diisopropyl ether, and then 2 times in 5 cm3ethyl acetate. After drying (90 PA; 50about(C) obtain 320 mg of N-[6-[4-(1,1-dimethylethyl)phenyl]-1H-indazol-3-yl]butanamide in the form of a white product melting at 246aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,99 (t, J= 7.5 Hz, 3H), of 1.36 (s, N), to 1.70 (m, 2H), 2,41 (t, J= 7 Hz, 2H), was 7.36 (d ush., J= 9 Hz, 1H), 7,52 (d, J= 8.5 Hz, 2H), to 7.61 (ush., 1H), 7,66 (l ush., J= 8.5 Hz, 2H), a 7.85 (d, J= 9 Hz, 1H), 10,32 (array, 1H), 12,66 (array, 1H).

Example 48

N-[6-Bromo-7-amino-1H-indazol-3-yl]butanamide

To 510 mg of N-[6-bromo-7-nitro-1H-indazol-3-yl]butanamide described in example 29, 20 cm3ethanol, while cooling to a temperature of 5aboutWith add dropwise a solution of 4.25 g of sulfate heptahydrate ferrous iron in 25 cm3water. The temperature is again increased until 28aboutC, stirred for 30 minutes, then add 5.2 cm328%ammonium hydroxide solution and refluxed for 2 hours, then add 2 more times to 1.5 cm328%ammonium hydroxide solution and stirred for 10 minutes, filtered in hot state when using a porous glass filter with telicom. The precipitate is washed with 20 cm3methanol filtrate concentrated to dryness under reduced pressure (2 kPa; 40aboutC). The residue is treated with 50 cm3ethyl acetate, washed with 25 cm3a saturated solution of sodium bicarbonate, then 25 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate and concentrate under reduced pressure (2 kPa; 40aboutC). After drying (90 PA; 50about(C) obtain 55 mg of N-[6-bromo-7-amino-1H-indazol-3-yl]-butanamide in a solid purple color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), 2,35 (t, J= 7 Hz, 2H), 5,47 (ush., 2H), 6,901 (d, J= 8.5 Hz, 1H), 7,00 (d, J= 8.5 Hz, 1H), 10,18 (ush., 1H), 12,38 (array, 1H).

Mass spectrum (EI): m/z = 296 M+;

m/z = 226 [M-C4H6O]+.

Example 49

N-[6-[4-(Trifluoromethyl)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 25, in 30 cm3dioxane add 775 mg 4-triftormetilfullerenov acid, 1.24 g of cesium fluoride, 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then refluxed for 18 hours, and then held until it reaches again the room temperature and the reaction medium is diluted with 75 cm3ethyl acetate, filtered through Stekla the hydrated porous filter telicom and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). Processing and purification carried out by analogy with example 41. Thus get 1 g of N-[6-[4-(trifluoromethyl)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil 95%purity.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), of 5.75 (s, 2H), 7,52 (d ush., J= 8.5 Hz, 1H), 7,88 (l ush., J= 8.5 Hz, 2H), of 7.97 (d, J= 8.5 Hz, 1H), 8,01 (l ush., J= 8.5 Hz, 2H), 8,07 (ush., 1H), 10,51 (array, 1H).

Mass spectrum (EI): m/z = 477 M+;

m/z = 360 [M-OCH2CH2Si(CH3)3]+;

m/z = 349 [M-C6H12OSi]+.

N-[6-[4-(Trifluoromethyl)phenyl]-1H-indazol-3-yl]butanamide

To a solution of 1 g of N-[6-[4-(trifluoromethyl)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide 30 cm3tetrahydrofuran (THF) add 12.6 cm3tetrabutylammonium-fluoride in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours. The reaction medium is diluted with 75 cm3ethyl acetate and the organic phase is washed successively with 2 times 50 cm3a saturated solution of sodium bicarbonate and 2 times 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50about C)receiving 0.95 g solid brown color. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving of 0.60 g of cream-colored crystals, which is treated with 10 cm3diisopropyl ether, filtered off and dried under reduced pressure (90 PA; 50aboutC)receiving of 0.47 g of N-[6-[4-(trifluoromethyl)phenyl]-1H-indazol-3-yl]butanamide in the form of white crystals, melting at a temperature above 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,41 (t, J= 7 Hz, 2H), 7,42 (DD, J= 9 and 1.5 Hz, 1H), 7,73 (ush., 1H), a 7.85 (d, J= 8.5 Hz, 2H), 7,92 (d, J= 9 Hz, 1H), of 7.97 (d, J= 8.5 Hz, 2H), 10,37 (array, 1H).

Example 50

N-[6-(4-Were)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 25, in 30 cm3dioxane add 555 mg 4-methylphenylacetic acid, 1.24 g of cesium fluoride, 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl, and then heated at a temperature of 104aboutC for 5 h the owls of 30 minutes and maintained at achieving again at room temperature for 16 hours. The reaction medium is diluted with 75 cm3ethyl acetate, filtered through a porous glass filter with telicom and the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC). Processing and purification carried out by analogy with example 41. Obtain 1.1 g of N-[6-(4-were)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), of 2.38 (s, 3H), 2,41 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), 5,73 (s, 2H), 7,32 (l ush., J= 8 Hz, 2H), 7,44 (l ush., J= 9 Hz, 1H), 7,68 (l ush., J= 8 Hz, 2H), of 7.90 (d, J= 9 Hz, 1H), 7,92 (ush., 1H), 10,46 (array, 1H).

Mass spectrum (EI): m/z = 423 M+;

m/z = 306 [M-OCH2CH2Si(CH3)3]+;

m/z = 295 [M-C6H12OSi]+.

N-[6-(4-Were)-1H-indazol-3-yl]butanamide

To a solution of 1.1 g of N-[6-(4-were)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) add 14.6 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The reaction medium is heated at a temperature of 66aboutC for 18 hours, then heating is stopped. In the reaction medium was added 75 cm3ethyl acetate and the organic phase is washed with 2 times 50 cm3saturated aqueous sodium hydrogen carbonate solution, then the use of 50 cm 3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of ethyl acetate and cyclohexane (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3diisopropyl ether, filtered and washed sequentially with 10 cm3diisopropyl ether, and then 3 times at 3 cm3ethyl acetate. After drying (90 PA; 50about(C)receive 500 mg of N-[6-(4-were)-1H-indazol-3-yl]butanamide in the form of a white product melting at 210aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (d, J= 7.5 Hz, 3H), 1.69 in (m, 2H), is 2.37 (s, 3H), 2.40 a (t, J= 7 Hz, 2H), 7,31 (d, J= 8 Hz, 2H), 7,35 (m, 1H), to 7.59 (ush., 1H), 7,63 (d, J= 8 Hz, 2H), a 7.85 (d, J= 9 Hz, 1H), 10,32 (ush., 1H), 12,65 (array, 1H).

Example 51

N-[6-Bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide

To a suspension of 1.1 g of sodium hydride (60 %in oil) in 20 cm3of dimethylformamide, cooled to a temperature of 0aboutWith add dropwise a solution of 6 g of N-(6-bromo-1H-indazol-3-yl)is butanamide, obtained according to example 24, 50 cm3of dimethylformamide, and then, at a temperature of 10aboutWith 4.5 cm3solution of 2-(trimethylsilyl)-ethoxymethylene 10 cm3of dimethylformamide and the reaction medium was held until it reaches room temperature. To the reaction medium, add 100 cm3ethyl acetate, then washed with 2 times 50 cm3water; the organic phase is decanted, dried over magnesium sulfate and concentrated to dryness under reduced pressure (2 kPa; 45aboutC)receiving of 6.9 g of solid substance. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira gradient of mixtures of cyclohexane and ethyl acetate (in a ratio of from 100:0 to 90:10 by volume). The fraction containing the target product, concentrated to dryness, obtaining 2.9 g of N-[6-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in a solid off-white color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,07 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 3,53 (t, J= 8 Hz, 2H), 5,67 (s, 2H), 7,29 (DD, J= 9 and 1.5 Hz, 1H), 7,82 (d, J= 9 Hz, 1H), 8,01 (d, J= 1.5 Hz, 1H), 10,54 (array, 1H).

Mass spectrum (EI): m/z = 411 M+;

m/z = 294 [M-OCH2CH2Si(CH3)3]+;

m/z = 283 [M-C6H12OSi]+.

N-[6-(3,5-Dichlorophenyl)-1-[[2-(trimethylsily is)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3dioxane type of 0.44 g of 3,5-dichlorophenylamino acid, 0.64 g of sodium carbonate in the form of a solution in 18 cm3water and 0,186 g of tetrakis-triphenylphosphine and refluxed for 18 hours. The reaction medium is diluted with 75 cm3ethyl acetate and 50 cm3water, then the medium is filtered through a porous glass filter with telicom and the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC). Processing and purification carried out by analogy with example 41. So get of 0.90 g of N-[6-(3,5-dichlorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow wax.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N)to 0.85 (t, J= 8 Hz, 2H), 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7 Hz, 2H), to 3.58 (t, J= 8 Hz, 2H), 5,77 (s, 2H), 7,53 (DD, J= 8.5 and 1.5 Hz, 1H), 7,66 (t, J= 2 Hz, 1H), 7,87 (d, J= 2 Hz, 2H), 7,95 (d, J= 8.5 Hz, 1H), 8,14 (ush., 1H), 10,51 (array, 1H).

Mass spectrum (EI): m/z = 477 M+;

m/z = 360 [M-OCH2CH2Si(CH3)3]+;

m/z = 349 [M-C6H12OSi]+.

N-[6-(3,5-Dichlorophenyl)-1H-indazol-3-yl]butanamide

To 1 g of N-[6-(3,5-dichlorophenyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 20 cm3tetrahydrofuran (THF) add 11,2 sup> 3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran, then the reaction medium is heated at a temperature of 65aboutC for 18 hours, then heated to stop and add 75 cm3ethyl acetate. The organic phase is washed with 2 times 50 cm3saturated aqueous sodium hydrogen carbonate solution, then with 50 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) obtain 290 mg of N-[6-(3,5-dichlorophenyl)-1H-indazol-3-yl]butanamide in the form of a white product.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 7,40 (l ush., J= 8.5 Hz, 1H), 7,63 (t, J= 2 Hz, 1H), 7,75 (ush., 1H), 7,81 (d, J= 2 Hz, 2H), 7,89 (d, J= 8.5 Hz, 1H), 10,37 (array, 1H), 12,70-12,95 (array ush., 1H).

Mass spectrum (EI): m/z = 347 M+; m/z = 277 [M-C4H6O]+.

Example 52

N-[6-Chloro-1H-indazol-3-yl] - for 3,5-dichlorobenzamide

To 1 g of 6-chloro-1H-indazol-3-amine in 15 cm3pyridine, after cooling in a bath with ice to a temperature of 3aboutTo add 0,83 cm33.5-dichlorobenzotrifluoride, then stirred for 10 minutes at this temperature and maintained at achieving again at room temperature for 18 hours. Reaction medium was then close tryout to dryness under reduced pressure (2 kPa; 50aboutC) and the residue is treated with 25 cm3ethyl acetate and 25 cm3water. The precipitation is filtered off and, after drying (90 PA; 50aboutTo obtain 700 mg of N-[6-chloro-1H-indazol-3-yl] - for 3,5-dichlorobenzamide in a solid white color, melting at 240aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 7,15 (DD, J= 8.5 and 2 Hz, 1H), 7,50-the 7.65 (m, 2H), 7,72 (d, J= 8.5 Hz, 1H), 7,79 (ush., 1H), of 7.90 (d, J= 8.5 Hz, 1H), 11,06 (ush., 1H).

Example 53

N-[6-(4-Chlorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 900 mg of N-[6-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 51, 40 cm3dioxane add 512 mg 4-Chlorfenvinphos acid, 578 mg of potassium carbonate and 167 mg tetranitroaniline. Then heated at a temperature of 104aboutWith over 2 hours and maintained at achieving again the temperature of the 19aboutC for 16 hours. The reaction medium is diluted with 75 cm3ethyl acetate, filtered through a porous glass filter with telicom and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 100 cm3ethyl acetate and 50 cm3water. The organic phase is again washed with 25 cm3saturated aqueous solution of sodium chloride, then decanted, dried over su is hatom magnesium, filtered and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under ponistena pressure (2 kPa; 50aboutC); receive 600 mg of N-[6-(4-chlorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow wax.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,41 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), 5,73 (s, 2H), 7,46 (l ush,, J= 9 Hz, 1H), 7,58 (d, J= 8.5 Hz, 2H), 7,81 (d, J= 8.5 Hz, 2H), to 7.93 (d, J= 9 Hz, 1H), 7,98 (ush., 1H), 10,49 (array, 1H).

Mass spectrum (EI): m/z = 443 M+;

m/z = 326 [M-OCH2CH2Si(CH3)3]+;

m/z = 315 [M-C6H12OSi]+.

N-[6-(4-Chlorophenyl)-1H-indazol-3-yl]butanamide

To a solution of 600 mg of N-[6-(4-chlorophenyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained above, 20 cm3tetrahydrofuran (THF) add 9.5 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran, then the reaction medium is heated at a temperature of 65aboutC for 18 hours, then heated to stop and add 40 cm3ethyl acetate. The organic phase is washed with 2 the Aza 30 cm 3saturated aqueous solution of sodium bicarbonate, then with 30 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) receive 238 mg of N-[6-(4-chlorophenyl)-1H-indazol-3-yl]butanamide in the form of a powder beige color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 7,35 (l ush., J= 8.5 Hz, 1H), 7,55 (d, J= 8.5 Hz, 2H), to 7.64 (ush., 1H), to 7.77 (d, J= 8.5 Hz, 2H), 7,88 (d, J= 8.5 Hz, 1H), 10,34 (array, 1H).

Mass spectrum (EI): m/z = 313 M+;

m/z = 243 [M-C4H6O]+.

Example 54

N-[6-Chloro-1H-indazol-3-yl]benzoyltrifluoroacetone

To 1 g of 6-chloro-1H-indazol-3-amine in 15 cm3pyridine, after cooling to a temperature of 5aboutTo add to 0.88 cm3hydrocinnamaldehyde, then incubated at achieving again at room temperature for 18 hours. Reaction medium was then concentrated to dryness under reduced pressure (2 kPa; 45aboutC), then treated with 25 cm3ethyl acetate, 25 cm3water and 10 cm3tetrahydrofuran (THF). Desantirovaniya the organic phase is washed with 25 cm3water, then 25 cm3saturated aqueous solution of sodium chloride; after drying over with what LifeCam magnesium, filtration and concentration to dryness under reduced pressure (2 kPa; 50about(C) the residue purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution 15-40 μm; diameter 4 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 97:3 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Received the contaminated product is again purified by high-performance liquid chromatography (column Hypurity; C18, 5 μm; length 50 mm, diameter 21 mm; eluting agent: gradient mixture of acetonitrile and water (in a ratio of from 5:95 to 95:5 by volume)containing 0.05 % triperoxonane acid; flow rate 10 cm3/min). After concentration of the fractions containing the desired product, get, after drying (90 PA; 50aboutC), 200 mg of N-[6-chloro-1H-indazol-3-yl]benzoyltrifluoroacetone in a solid white color, melting at 224aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,73 (t, J= 7.5 Hz, 2H), 2,97 (t, J= 7.5 Hz, 2H), 7,06 (DD, J= 9 and 1.5 Hz, 1H), 7,15-7,40 (m, 5H), 7,51 (d, J= 1.5 Hz, 1H), to 7.77 (d, J= 9 Hz, 1H), 10,44 (ush., 1H).

Example 55

N-[6-(4-Ethylphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 25, in 30 cm dioxane add 612 mg 4-ethylvinylbenzene acid, 1.24 g of cesium fluoride, 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl, and then refluxed for 16 hours. The reaction medium is diluted with 50 cm3ethyl acetate and 50 cm3water, filtered through a porous glass filter with telicom and the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC). Processing and purification carried out by analogy with example 41. Even the contaminated product is again purified by high-performance liquid chromatography (column Hypurity; C18, 5 μm; length 50 mm, diameter 21 mm; eluting agent: a mixture of acetonitrile and water containing 0.05 % triperoxonane acid; flow rate 10 cm3/min). After concentration of fractions containing the target product, and drying (90 PA; 45about(C) obtain 240 mg of N-[6-(4-ethylphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil. The product is injected directly to the next stage.

N-[6-(4-Ethylphenyl)-1H-indazol-3-yl]butanamide

To a solution of 240 mg of N-[6-(4-ethylphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 20 cm3tetrahydrofuran (THF) added 3.3 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The medium is then heated at a temperature which round 67 aboutC for 17 hours, then held until it reaches again the room temperature and add 50 cm3ethyl acetate. The organic phase is washed with 2 times 50 cm3saturated aqueous sodium hydrogen carbonate solution, 2 times 50 cm3water, decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3diisopropyl ether, filtered off on a glass Frit and washed sequentially with 2 cm3ethyl acetate, then 10 cm3diisopropyl ether. After drying (90 PA; 50about(C) receive 80 mg of N-[6-(4-ethylphenyl)-1H-indazol-3-yl]butanamide in a solid white color, melting at 210aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), 1,24 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,39 (t, J= 7 Hz, 2H), to 2.67 (d, J= 7.5 Hz, 2H), 7,30-7,40 (m, 3H), to 7.59 (ush., 1H), 7,65 (l ush., J= 8 Hz, 2H), to 7.84 (d, J= 9 Hz, 1H), 10,31 (array, 1H), 12,65 (array, 1H).

Example 56

N-[6-(4,4,5,5-Tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 740 mg of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 25, 25 cm3dioxane add 766 mg bis(pinacolato)DIBORANE, 917 mg of cesium fluoride, and then to 9.9 mg of palladium acetate and finally, to 23.6 mg 2-dicyclohexylphosphino-2-(N,N-dimethylamino)diphenyl. The medium is refluxed for 20 hours, then held until it reaches again the room temperature and add 50 cm3ethyl acetate and 50 cm3water. After filtration of the reaction medium through a porous glass filter with telicom washed with 2 times 50 cm3water. The organic phase is dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 630 mg of N-[6-(4,4,5,5-tetramethyl[1,3,2]-dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, 9 is), of 0.82 (t, J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), of 1.34 (s, N), to 1.67 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 3,50 (t, J= 8 Hz, 2H), 5,71 (s, 2H), 7,39 (d, J= 8.5 Hz, 1H), 7,83 (d, J= 8.5 Hz, 1H), of 7.97 (s, 1H), 10,45 (array, 1H).

Mass spectrum (EI): m/z = 459 M+;

m/z = 342 [M-OCH2CH2Si(CH3)3]+;

m/z = 331 [M-C6H12OSi]+;

m/z = 272 [342-C4H6O]+.

N-[6-(4-Pyridinyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 320 mg of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide described above, in 20 cm3dioxane is added 246 mg of 4-iodopyridine, 10 cm3water, 201 mg sodium carbonate and 69 mg tetranitroaniline. The medium is then refluxed for 20 hours, and then held until it reaches again the room temperature and add 50 cm3ethyl acetate and 50 cm3water. The combined organic phases are washed with 50 cm3distilled water, then 50 cm3saturated aqueous solution of sodium chloride, then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fraction that contains Asia target product, combined and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 280 mg of N-[6-(4-pyridinyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: one - 0.10 (s, N), or 0.83 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7 Hz, 2H), only 3.57 (t, J= 8 Hz, 2H), USD 5.76 (s, 2H), EUR 7.57 (DD ush., J= 8.5 and 1 Hz, 1H), 7,82 (l ush., J= 6 Hz, 2H), 7,98 (d, J= 8.5 Hz, 1H), 8,16 (ush., 1H), 8,70 (d ush., J= 6 Hz, 2H), 10,52 (array, 1H).

Mass spectrum (EI): m/z = 410 M+;

m/z = 293 [M-OCH2CH2Si(CH3)3]+;

m/z = 282 [M-C6H12OSi]+.

N-[6-(4-Pyridinyl)-1H-indazol-3-yl]butanamide

To 280 mg of N-[6-(4-pyridinyl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 20 cm3tetrahydrofuran (THF) add 4.1 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran, then the medium is heated at a temperature of 67aboutC for 17 hours, then held until it reaches again the room temperature and add 50 cm3ethyl acetate and 50 cm3saturated aqueous solution of sodium bicarbonate. The organic phase is washed with 50 cm3saturated aqueous solution of sodium chloride, then 50 cm3water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The mod is to purify by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira with ethyl acetate. The fractions containing the desired product are pooled and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3diisopropyl ether, filtered off on a glass Frit and then washed sequentially with 5 cm3ethyl acetate and 10 cm3diisopropyl ether. After drying (90 PA; 50about(C) receive 60 mg of N-[6-(4-pyridinyl)-1H-indazol-3-yl]butanamide in a solid white color, melting at 200aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,41 (t, J= 7 Hz, 2H), 7,47 (DD ush., J= 9 and 1 Hz, 1H), 7,78 (l ush., J= 6 Hz, 2H), 7,81 (ush., 1H), to 7.93 (d, J= 9 Hz, 1H), 8,67 (l ush., J= 6 Hz, 2H), 10,38 (array, 1H), 12,84 (ush., 1H).

Example 57

N-(5-Amino-1H-indazol-3-yl)butanamide

To a solution of 2.05 g of N-[5-nitro-1H-indazol-3-yl]butanamide described in example 23, 80 cm3ethanol is added 20 g of iron sulfate heptahydrate dissolved in 50 cm3hot water, stirred for 30 minutes at room temperature and add 24 cm328%ammonium hydroxide solution, and then refluxed for 2 hours, add another 10 cm328%ammonium hydroxide solution and stirred for 10 minutes. The precipitate is filtered off in the city is hot condition on a glass Frit with telicom, washed with methanol until then, until the filtrate becomes colorless, and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 100 cm3ethyl acetate and washed with 50 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. After drying (90 PA; 50about(C) obtain 870 mg of N-(5-amino-1H-indazol-3-yl)butanamide in the form of a powder purple color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,34 (t ush., J= 7 Hz, 2H), 4,82 (array, 2H), 6,70 (ush., 1H), 6,77 (DD, J= 9 and 2 Hz, 1H), 7,15 (d, J= 9 Hz, 1H), 9,92 (array, 1H), 12,13 (array, 1H).

Mass spectrum (EI): m/z = 218 M+;

m/z = 148 [M-C4H6O]+;

m/z = 43 [C3H7]+.

Example 58

N-[5-Bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 25, 15 cm3chloroform add to 0.22 cm3pyridine, then add to 0.14 cm3bromine. Stirred for 24 hours at a temperature of 20aboutWith, then add 50 cm3dichloromethane and 50 cm3saturated aqueous solution of sodium sulfate. After stirring for 10 minutes nearest oriau part is removed by filtration on a glass Frit and the organic phase is washed with 50 cm 3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) receive 940 mg of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in a solid white color, melting at 130aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), of 0.82 (t, J= 8 Hz, 2H), of 0.95 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2.40 a (t, J= 7.5 Hz, 2H), 3,52 (t, J= 8 Hz, 2H), to 5.66 (s, 2H), 8,13 (s, 1H), 8.34 per (s, 1H), 10,67 (ush., 1H).

N-(5-Bromo-6-chloro-1H-indazol-3-yl)butanamide

To 940 mg of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) add 12.6 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. Then the medium is heated at a temperature of 67aboutC for 19 hours, then held until it reaches again the room temperature and add 50 cm3etelaat the and. The organic phase is washed with 2 times 50 cm3saturated aqueous sodium hydrogen carbonate solution, then with 50 cm3saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 15 cm3di-isopropyl ether, filtered off on a glass Frit, washed sequentially with 5 cm3ethyl acetate, then 2 x 10 cm3diisopropyl ether. After drying (90 PA; 50aboutC) get 460 mg of N-(5-bromo-6-chloro-1H-indazol-3-yl]butanamide in a solid white color, melting at 250aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm as 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), to 7.77 (s, 1H), 8,29 (s, 1H), 10,53 (array, 1H), 12,50-13,20 (array ush., 1H).

Example 59

N-[6-Chloro-1H-indazol-3-yl]-2-thiophencarboxylic

To 1 g of 6-chloro-1H-indazol-3-amine in 15 cm3pyridine, after cooling to a temperature of 6aboutWith n the bath with ice, add 0,64 cm32-thiophenecarbonitrile, then incubated at achieving again at room temperature for 17 hours and the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 45aboutC), then the residue is treated with 20 cm3ethyl acetate, 20 cm3water and 20 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC), after which the residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution 15-40 μm; diameter 3 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 99:1 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); after drying (90 PA; 50about(C) obtain 660 mg of N-(6-chloro-1H-indazol-3-yl]-2-thiophenecarboxylate in the form of solids blignault color, melting at 215aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 7,11 (DD, J= 9 and 2 Hz, 1H), 7,25 (DD, J= 5 and 3.5 Hz, 1H), 7,58 (DD, J= 2 and 0.5 Hz, 1H), 7,81 (DD, J= 9 and 0.5 Hz, 1H), of 7.90 (DD, J= 5 and 1.5 Hz, 1H), 8,14 (DD, J= 3.5 and 1.5 Hz, 1H), 10,98 (array, 1H), 12,96 (array, 1H).

Example 60

N-(6-Chloro-1H-indazol-3-yl)-2-methylpropanamide

To 1 g of 6-chloro-1H-indazol-3-amine in 15 cm3pyridine is, after cooling the medium to a temperature of 6aboutTo add 0,63 cm3isobutyramide, then incubated at achieving again at room temperature for 19 hours and evaporated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is treated with 25 cm3ethyl acetate and 25 cm3water; the precipitation is filtered off on a glass Frit and then washed with ethyl acetate. After drying (90 PA; 50about(C) obtain 384 mg of N-(6-chloro-1H-indazol-3-yl)-2-methylpropylamine in the form of a white product melting at 238aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1,17 (d, J= 7 Hz, 6N), a 2.75 (m, 1H), was 7.08 (DD, J= 9 and 1.5 Hz, 1H), 7,52 (ush., 1H), 7,82 (d, J= 9 Hz, 1H), 10,35 (ush., 1H), 12,76 (ush., 1H).

Example 61

4-Chloro-N-(6-chloro-1H-indazol-3-yl)butanamide

To 1 g of 6-chloro-1H-indazol-3-amine in 15 cm3pyridine, after cooling to a temperature of 6aboutWith in a bath with ice, add to 0.67 cm34-chlorobutyronitrile, then incubated at achieving again at room temperature for 19 hours and the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is treated with 25 cm3ethyl acetate and 25 cm3water. The precipitate is filtered off, washed with 15 cm3ethyl acetate and 5 cm3dichloromethane. Organic f the zu dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2 kPa; 45aboutC); after drying (90 PA; 50about(C) obtain 343 mg of 4-chloro-N-(6-chloro-1H-indazol-3-yl)butanamide in the form of a solid pale yellow color, melting at 220aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,09 (m, 2H), 2,58 (t, J= 7 Hz, 2H), 3,74 (t, J= 7 Hz, 2H), was 7.08 (DD ush., J= 9 and 1.5 Hz, 1H), 7,52 (d ush., J= 1.5 Hz, 1H), to 7.84 (d, J= 9 Hz, 1H), 10,51 (ush., 1H), 12,60-13,10 (array ush., 1H).

Example 62

N-[5-Phenyl-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 2 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 58, 180 cm3dioxane add 821 mg of phenylboronic acid, 1,14 g of sodium carbonate in 30 cm3distilled water and, finally, 347 mg tetranitroaniline. Refluxed for 90 minutes, then held until it reaches again the temperature of 20aboutC and add 100 cm3ethyl acetate and 100 cm3of distilled water. The organic phase is washed with 100 cm3saturated aqueous solution of sodium chloride, then decanted and dried over magnesium sulfate. After filtration, the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC) and the residue is purified by chromatography under a pressure of argon 5 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) receive 2 g of N-[5-phenyl-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N)to 0.85 (t, J= 8 Hz, 2H), to 0.92 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), of 2.38 (t, J= 7.5 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), 5,70 (s, 2H), 7,30-of 7.55 (m, 5H), to $ 7.91 (s, 1H), to 7.99 (s, 1H), 10,59 (ush., 1H).

Mass spectrum (EI): m/z = 443 M+;

m/z = 326 [M-OCH2CH2Si(CH3)3]+;

m/z = 315 [M-C6H12OSi]+.

N-(5-Phenyl-6-chloro-1H-indazol-3-yl)butanamide

To 650 mg of N-[5-phenyl-6-chloro-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 25 cm3tetrahydrofuran (THF) add 8,8 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. Then the medium is heated at a temperature of 67aboutC for 20 hours, then held until it reaches again the room temperature and add 75 cm3ethyl acetate; the organic phase is washed with 75 cm3saturated aqueous sodium hydrogen carbonate solution, and then 2 times in 75 cm3saturated aqueous solution of sodium chloride. The organic phase sushi is t over magnesium sulfate, filtered and evaporated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 15 cm3diisopropyl ether, filtered off on a glass Frit and washed sequentially with 10 cm3diisopropyl ether and 5 cm3ethyl acetate. After drying under reduced pressure (90 PA; 50about(C) obtain 240 mg of N-(5-phenyl-6-chloro-1H-indazol-3-yl]butanamide in a solid white color, melting at 235aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.92 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), 2,37 (t, J= 7 Hz, 2H), 7,35-of 7.55 (m, 5H), 7,66 (s, 1H), a 7.85 (s, 1H), 10,47 (ush., 1H), 12,80 (array, 1H).

Example 63

N-[5-Bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 2.64 g of N-[6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to example 32, 50 cm3chloroform add 0,84 cm3pyridine, then added dropwise to the value of 0.52 cm3bromine, then again 0,42 cm3PI is Idina and 0.26 cm 3bromine. To the reaction medium add 50 cm3dichloromethane and 100 cm310%sodium thiosulfate solution; the organic phase is decanted, washed sequentially with 50 cm310%sodium thiosulfate solution and 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC)obtaining 3.4 g of an oil which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)obtaining 2.1 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a white powder, melting at 140aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), 0,81 (t, J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2,42 (t ush., J= 7 Hz, 2H), 3,53 (t, J= 8 Hz, 2H), 5,19 (s, 2H), 5,67 (s, 2H), 7,13 (d, J= 8.5 Hz, 2H), 7,37 (d, J= 8.5 Hz, 2H), 7,37 (m, 1H), 7,43 (t ush., J= 7.5 Hz, 2H), 7,51 (l ush., J= 7.5 Hz, 2H), of 7.70 (s, 1H), compared to 8.26 (s, 1H), 10,61 (array, 1H).

N-[5-Bromo-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

To 2 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide is, as described above, in 60 cm3tetrahydrofuran (THF) add 20 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 75 cm3ethyl acetate and the organic phase is washed successively with 75 cm3a saturated solution of sodium bicarbonate and 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa; 50aboutC)receiving 2 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 50 cm3di-isopropyl ether, filtered off, washed with 2 times 10 cm3diisopropyl ether and dried (90 PA; 50aboutC)receiving 500 mg of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide in the form of a solid, melting at 200aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7 Hz, 2H), 5,19 (s, 2H), 7,12 (d, J= 8.5 Hz, 2H) 7,30-to 7.50 (m, 6N), 7,53 (l ush., J= 7.5 Hz, 2H), by 8.22 (s, 1H), 10,50 (array, 1H), 12,83 (array, 1H).

N-[5-Bromo-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide

To 500 mg of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide obtained above, add 10 cm3trimethylsilylmethyl and refluxed for 4 hours. In medium was added to 25 cm3methanol and again refluxed for 15 minutes, then the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 50 cm3ethyl acetate and washed with 2 times 50 cm310%sodium thiosulfate solution, then with 50 cm3water and 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure, obtaining 1 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3ethyl acetate, filtered off, washed with 2 times 5 cm3ethyl acetate and dried (90 PA; 45aboutC)receiving 10 mg of N-[5-bromo-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide, melting at a temperature above 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 6,85 (d, J= 8.5 Hz, 2H), 7,25 (d, J= 8.5 Hz, 2H), 7,34 (s, 1H), to 8.20 (s, 1H), being 9.61 (array, 1H), 10,48 (ush., 1H), 12,79 (array, 1H).

Example 64

N-[6-(4-Nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, obtained as described in example 56, 50 cm3dioxane is added 790 mg of 4-bromonitromethane, 10 cm3water, 646 mg of sodium carbonate and 190 mg tetranitroaniline. The reaction medium is then refluxed for 18 hours and held until it reaches again at room temperature, then add 75 cm3ethyl acetate and the organic phase is washed with 2 times 50 cm3distilled water, then with 50 cm3saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, filtering and concentrating to dryness under reduced pressure (2 kPa; 45about(C) the residue purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fraction containing the target product, which are United by and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 650 mg of N-[6-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: one - 0.10 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,42 (t, J= 7 Hz, 2H), only 3.57 (t, J= 8 Hz, 2H), 5,77 (s, 2H), 7,56 (DD ush., J= 9 and 1.5 Hz, 1H), to 7.99 (d, J= 9 Hz, 1H), of 8.09 (d, J= 9 Hz, 2H), 8,15 (ush., 1H), of 8.37 (d, J= 9 Hz, 2H), 10,56 (array, 1H).

Mass spectrum (EI): m/z = 454 M+;

m/z = 337 [M-OCH2CH2Si(CH3)3]+;

m/z = 326 [M-C6H12OSi]+;

m/z = 73 [Si(CH3)3]+.

N-[6-(4-Nitrophenyl)-1H-indazol-3-yl]butanamide

To 650 mg of N-[6-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) add 8.6 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran, then the medium is heated at a temperature of 67aboutC for 18 hours, and then held until it reaches again the room temperature and add 75 cm3ethyl acetate and 75 cm3saturated aqueous solution of sodium bicarbonate. The organic phase is washed with 50 cm3saturated aqueous solution of sodium chloride, then 50 cm3water, decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified is by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled and concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3ethyl acetate, filtered off on a glass Frit and then washed sequentially with 5 cm3ethyl acetate and 10 cm3diisopropyl ether. After drying (90 PA; 50about(C) obtain 280 mg of N-[6-(4-nitrophenyl)-1H-indazol-3-yl]butanamide in the form of yellow crystals, melting at 250aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,41 (t, J= 7 Hz, 2H), 7,46 (DD, J= 8.5 and 1.5 Hz, 1H), 7,79 (ush., 1H), 7,94 (d, J= 8.5 Hz, 1H), 8,05 (l ush., J= 9 Hz, 2H), 8.34 per (l ush., J= 9 Hz, 2H), 10,42 (array, 1H), 12,87 (ush., 1H).

Example 65

N-[6-(2-Chlorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 51, 60 cm3dioxane add 853 mg of 2-Chlorfenvinphos acid, 30 cm3water, 964 mg of sodium carbonate and 252 mg tetranitroaniline. The reaction medium is then refluxed for 18 hours and filtered through a porous glass filter with telicom, then concentrate to dryness at pony is hinnon pressure (2 kPa; 50aboutC). The residue is treated with 70 cm3ethyl acetate and the organic phase is washed with 2 times 30 cm3distilled water, then using a 30 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The resulting residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); receive 1 g of N-[6-(2-chlorophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide in the form of a yellow wax.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), from 0.84 (t, J= 8 Hz, 2H), 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,43 (t, J= 7 Hz, 2H), only 3.57 (t, J= 8 Hz, 2H), 5,71 (s, 2H), 7,19 (DD, J= 8.5 and 2 Hz, 1H), 7,40-of 7.70 (m, 4H), 7,74 (ush., 1H), of 7.90 (d, J= 8.5 Hz, 1H), 10,51 (array, 1H).

Mass spectrum (EI): m/z = 443 M+;

m/z = 326 [M-OCH2CH2Si(CH3)3]+;

m/z = 315 [M-C6H12OSi]+.

N-[6-(2-Chlorophenyl)-1H-indazol-3-yl]butanamide

To 900 mg of N-[6-(2-chlorophenyl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 40 cm3tetrahed is furana add 2.9 cm 3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours. The reaction medium is diluted with 50 cm3ethyl acetate and the organic phase is washed successively with 2 times 30 cm3a saturated solution of sodium bicarbonate, with 30 cm3water and 30 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); receive 120 mg of N-[6-(2-chlorophenyl)-1H-indazol-3-yl]butanamide in the form of a solid foam beige color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 7,09 (l ush., J= 8.5 Hz, 1H), 7,40-the 7.65 (m, 5H), 7,83 (d, J= 8.5 Hz, 1H), 10,36 (ush., 1H), 12,74 (ush., 1H).

Mass spectrum (EI): m/z = 313 M+;

m/z = 243 [M-C4H6O]+.

Example 66

N-[6-[3-(Phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(Tr is methylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, obtained according to example 25, successively added 930 mg 3-benzyloxypropionic acid, 1.24 g of cesium fluoride, 31,5 mg 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)diphenyl, 13.5 mg of palladium acetate and refluxed for 18 hours. The reaction medium is filtered through a porous glass filter with telicom and to the filtrate add 75 cm3ethyl acetate. The organic phase is washed with 25 cm3a saturated solution of sodium chloride, decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in a ratio of from 90:10 to 75:25 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 1.1 g of N-[6-[3-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide in the form of oil 80%purity.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N)to 0.85 (t, J= 8 Hz, 2H), 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7 Hz, 2H), to 3.58 (t, J= 8 Hz, 2H), 5,23 (s, 2H), of 5.75 (s, 2H), was 7.08 (DD ush., J= 8.5 and 2 Hz, 1H), 7,30-to 7.50 (m, 7H), 7,53 (l ush., J= 7.5 Hz, 2H), 7,92 (d, J= 9 Hz, 1H), of 7.96 (ush., 1H), 10,48 (array, 1H).

Mass spectrum (desor the conservation and chemical ionization (DCI): m/z = 516 [M+H] +.

N-[6-[3-(Phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-[3-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 20 cm3tetrahydrofuran (THF) added 2.9 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours. The reaction medium is diluted with 100 cm3ethyl acetate and the organic phase is washed successively with 50 cm3a saturated solution of sodium bicarbonate, 2 x 50 cm3of water and with 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira gradient of mixtures of cyclohexane and ethyl acetate (in a ratio of from 70:30 to 40:60 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); gain of 0.43 g of N-[6-[3-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of white powder.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), with 5.22 (s, 2H), 7,05 (DD ush., J= 8.5 and 2 Hz, 1H), 7.5 to to 7.50 (m, 7H), 7,52 (d ush., J= 7.5 Hz, 2H), 7,63 (ush., 1H), 7,35 (d, J= 9 Hz, 1H), 10,33 (array, 1H), 12,68 (array, 1H).

Mass spectrum (EI): m/z = 385 M+;

m/z = 315 [M-C4H6O]+.

N-[6-(3-Hydroxyphenyl)-1H-indazol-3-yl]butanamide

To 0.4 g of N-[6-[3-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide described above, add 10 cm3trimethylsilylmethyl and refluxed for 3 hours, then add 50 cm3methanol and continue boiling under reflux for 15 minutes. Reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC)add 50 cm3ethyl acetate and the organic phase is washed with 3 times 50 cm310%sodium thiosulfate solution. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutS); obtain 0.18 g of N-[6-(3-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of a gray powder, melting at 188aboutC.

1H-NMR spectrum (300 MHz, (CD3 2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 6,80 (DD ush., J= 8 and 2 Hz, 1H), was 7.08 (m, 1H), 7,13 (l ush., J= 8 Hz, 1H), 7,25-7,35 (m, 2H), 7,55 (ush., 1H), to 7.84 (d, J= 8.5 Hz, 1H), of 9.55 (ush., 1H), 10,34 (array, 1H), 12,67 (array, 1H).

Example 67

N-[6-Chloro-5-(4-pyridinyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 58, 90 cm3dioxane add 415 mg 4-pyridylamino acid, then the solution of 570 mg of sodium carbonate in 18 cm3water and, finally, 173 mg tetranitroaniline and refluxed for 18 hours. The reaction medium is diluted with 75 cm3ethyl acetate and 50 cm3water. The organic phase is decanted, washed with 50 cm3water and 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutS); obtain 770 mg of N-[6-chloro-5-(4-pyridinyl)-1-[[2-(trimethylsily is)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of white crystals.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N)to 0.85 (t, J= 8 Hz, 2H), of 0.93 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 3,55 (t, J= 8 Hz, 2H), 5,71 (s, 2H), of 7.48 (d ush., J= 6 Hz, 2H), 7,98 (s, 1H), 8,08 (s, 1H), 8,69 (l ush., J= 6 Hz, 2H), 10,67 (array, 1H).

Mass spectrum (ei electron spray (ES): m/z = 445 [M+H]+.

N-[6-Chloro-5-(4-pyridinyl)-1H-indazol-3-yl]butanamide

To 770 mg of N-[6-chloro-5-(4-pyridyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) type 10.4 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours. The reaction medium is diluted with 75 cm3ethyl acetate and 75 cm3a saturated solution of sodium bicarbonate. The organic phase is decanted, washed with 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with ethyl acetate. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 20 cm3ethyl acetate, filtered off, washed with whom omashu 5 cm 3ethyl acetate and 20 cm3diethyl ether, dried under reduced pressure (90 PA; 45aboutC)receiving 320 mg of N-[6-chloro-5-(4-pyridinyl)-1H-indazol-3-yl]butanamide in the form of white crystals, melting at a temperature above 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,93 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), of 2.38 (t, J= 7 Hz, 2H), 7,47 (DD, J= 5 and 1.5 Hz, 2H), 7,71 (s, 1H), 7,94 (s, 1H), 8,67 (DD, J= 5 and 1.5 Hz, 2H), 10,53 (array, 1H), 12,90 (ush., 1H).

Example 68

N-[6-Chloro-5-(3-furanyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 58, 90 cm3dioxane add 377 mg 3-Puilboreau acid, then 570 mg of sodium carbonate in 18 cm3water and, finally, 173 mg tetranitroaniline and refluxed for 18 hours. The reaction medium is diluted with 75 cm3ethyl acetate and 50 cm3water. The organic phase is decanted, washed with 50 cm3water and 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira is a mixture of cyclohexane and ethyl acetate (ratio of 85:15 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); receive 800 mg of N-[6-chloro-5-(3-furanyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a colorless oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,06 (s, N), from 0.84 (t, J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,41 (t ush., J= 7 Hz, 2H), 3,55 (t, J= 8 Hz, 2H), 5,69 (s, 2H), 6,79 (m, 1H), 7,80 (t, J= 2 Hz, 1H), 7.95 is-with 8.05 (m, 3H), 10,59 (array, 1H).

Mass spectrum (ES): m/z = 456 [M+Na]+;

m/z = 434 [M+H]+;

m/z = 326 [M-OCH2CH2Si(CH3)3]+.

N-[6-chloro-5-(3-furanyl)-1H-indazol-3-yl]butanamide

To 800 mg of N-[6-chloro-5-(3-furanyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3tetrahydrofuran (THF) added 11 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours. The reaction medium is diluted with 75 cm3ethyl acetate and 50 cm3a saturated solution of sodium bicarbonate. The organic phase is decanted, washed with 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (gr who nanometre 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 25 cm3diethyl ether, filtered off, washed with 2 times 10 cm3diethyl ether, dried under reduced pressure (90 PA; 45aboutC)receiving 220 mg of N-[6-chloro-5-(3-furanyl)-1H-indazol-3-yl]butanamide in the form of white crystals, melting at 250aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), 2,39 (t ush., J= 7 Hz, 2H), 6,76 (ush., 1H), to 7.64 (s, 1H), 7,78 (t, J= 1.5 Hz, 1H), 7,95 (m, 2H), 10,94 (array, 1H), 12,50-13,00 (array ush., 1H).

Example 69

1-Bromo-2-chloro-4-(phenylmethoxy)benzene

To 480 mg of sodium hydride (60%in oil) in 10 cm3of dimethylformamide is added 2 g of 4-bromo-3-chlorophenol in the form of a solution in 20 cm3of dimethylformamide, then add a solution of 1.38 cm3benzylchloride 5 cm3of dimethylformamide. Reaction medium was concentrated under reduced pressure and treated with 100 cm3ethyl acetate. The organic phase is washed successively with 2 times 50 cm3of water and with 50 cm3a saturated solution of sodium chloride, decanted, dried over magnesium sulfate, filter and concentrate Dosh is under reduced pressure (2 kPa; 50aboutC)receiving 3 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Get 2,63 g of 1-bromo-2-chloro-4-(phenylmethoxy)benzene in the form of an orange oil, which crystallizes.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 5,16 (s, 2H), 6,99 (DD, J= 9 and 3 Hz, 1H), 7,34 (d, J= 3 Hz, 1H), 7,35-of 7.55 (m, 5H), the 7.65 (d, J= 9 Hz, 1H).

Mass spectrum (EI): m/z = 296 M+.

N-[6-[2-Chloro-4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 2 g of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 56, 180 cm3dioxane type of 1.95 g of 1-bromo-2-chloro-4-(phenylmethoxy)benzene described above, 1,11 g of sodium carbonate in 36 cm3water and 347 mg tetranitroaniline. The medium is then refluxed for 2 hours, incubated until reaching again the room temperature and add 200 cm3ethyl acetate, 100 cm3water and filtered through a porous glass filter with telicom. The combined organic phases are washed with 100 cm 3distilled water, then 100 cm3saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio of 85:15 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Gain of 1.34 g of N-[6-[2-chloro-4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), or 0.83 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7 Hz, 2H), 3,55 (t, J= 8 Hz, 2H), 5,23 (s, 2H), 5,70 (s, 2H), 7,13 (DD, J= 8.5 and 2.5 Hz, 1H), 7,15 (d ush., J= 8.5 Hz, 1H), 7,30 (d, J= 2.5 Hz, 1H), 7,35-of 7.55 (m, 6N), 7,69 (ush., 1H), 7,86 (d, J= 8.5 Hz, 1H), 10,51 (array, 1H).

Mass spectrum (EI): m/z = 549 M+;

m/z = 432 [M-OCH2CH2Si(CH3)3]+;

m/z = 421 [M-C6H12OSi]+.

N-[6-[2-Chloro-4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

To 1.3 g of N-[6-[2-chloro-4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 60 cm3tetrahydrofuran (THF) add 14.2 cm3tetrabutylammonium 1 M dissolve is in tetrahydrofuran and refluxed for 18 hours; after cooling, add 75 cm3ethyl acetate and the organic phase is washed successively with 50 cm3a saturated solution of sodium bicarbonate and 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)obtaining 1.8 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3diisopropyl ether, filtered off, washed with 2 times 10 cm3diisopropyl ether and dried under reduced pressure (90 PA; 45aboutC)receiving 600 mg of N-[6-[2-chloro-4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of white crystals.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), with 5.22 (s, 2H), 7,06 (l ush., J= 8.5 Hz, 1H), 7,11 (DD, J= 8.5 and 2.5 Hz, 1H), 7,27 (d, J= 2.5 Hz, 1H), 7,35-of 7.55 (m, 7H), 7,79 (d, J= 8.5 Hz, 1H), 10,35 (array, 1H), 12,69 (array, 1H).

Mass spectrum (EI): m/z = 419 M+;

m/z = 349 [M-C4H6O]+.

N-[6-(2-Chloro-4-hydroxyphenyl is)-1H-indazol-3-yl]butanamide

To 0.6 g of N-[6-[2-chloro-4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide described above, add 15 cm3trimethylsilylmethyl and refluxed for 4 hours, then add 50 cm3methanol and continue boiling under reflux for 15 minutes. Reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC)add 100 cm3ethyl acetate and the organic phase is washed with 2 times 50 cm310%sodium thiosulfate solution, then with 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness. The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutS); obtain 0.24 g of N-[6-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of a solid white foam.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6), d in ppm: of 0.90 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 6,86 (DD, J= 8.5 and 2 Hz, 1H), 6,97 (d, J= 2 Hz, 1H), 7,05 (l ush., J= 9 Hz, 1H), 7,30 (d, J= 8.5 Hz, 1H), 7,37 (s, 1H), 7,78 (d, J= 9 Hz, 1H), 10,02 (array, 1H), 10,33 (ush., 1H), 12,65 (ush., 1H).

M is SS-spectrum (EI): m/z = 329 M +;

m/z = 259 [M-C4H6O]+.

Example 70

N-[5,6-Dibromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 4 g of N-[6-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 51, 80 cm3chloroform add 3.3 cm3pyridine and added dropwise to 2 cm3bromine, then aged with stirring for 18 hours. The reaction medium is diluted with 100 cm3dichloromethane and the organic phase is washed with 2 times 100 cm310%sodium thiosulfate solution, then using a 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC), then dried (90 PA; 45aboutC)receiving 4,24 g of N-[5,6-dibromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in a solid yellow color, melting at 134aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6, d in ppm: to 0.08 (s, N), 0,81 (t, J= 8 Hz, 2H), of 0.95 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 3,52 (t, J= 8 Hz, 2H), to 5.66 (s, 2H), compared to 8.26 (s, 1H), with 8.33 (s, 1H), 10,66 (array, 1H).

N-[5,6-Dibromo-1H-indazol-3-yl]butanamide

To 1 g of N-[5,6-dibromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 60 cm3tetrahydrofuran (THF) add 12.2 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 75 cm3ethyl acetate and the organic phase is washed successively with 100 cm3a saturated solution of sodium bicarbonate, then 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)obtaining 1.6 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 20 cm3diisopropyl ether, filtered off, washed with 2 times 10 cm3diisopropyl ether and dried (90 PA; 45aboutC)receiving 460 m is N-[5,6-dibromo-1H-indazol-3-yl]butanamide in the form of blue crystals, melting at 250aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,39 (t, J= 7 Hz, 2H), to $ 7.91 (s, 1H), 8,28 (s, 1H), 10,55 (array, 1H), 12,70-13,20 (array ush., 1H).

Example 71

N-[6-Chloro-1H-indazol-3-yl]-2,2,3,3,4,4,4-getattributename

To 1 g of 6-chloro-1H-indazol-3-amine in 10 cm3pyridine, after cooling medium to a temperature of 6aboutTo add to 0.60 cm3heptafluorobutyrate, then incubated at achieving again at room temperature for 19 hours and evaporated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is treated with 40 cm3ethyl acetate and 20 cm3water; the precipitation is filtered off on a glass Frit and then washed with 2 times 10 cm3dichloromethane and purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving of 0.77 g of N-[6-chloro-1H-indazol-3-yl]-2,2,3,3,4,4,4-getattributename in the form of wool.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 7,19 (DD ush., J= 9 and 1.5 Hz, 1H), 7.62mm (d, J= 9 Hz, 1H), to 7.64 (ush., 1H), 12,09 (array, 1H), 13,25 (array, 1H).

Mass spectrum (EI): m/z = 363 M ;

m/z = 194 [M-CF2CF2CF3]+;

m/z = 166 [M-COCF2CF2CF3]+.

Example 72

N-[5-(4-Forfinal)-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 58, 40 cm3dioxane add 470 mg of 4-ftorhinolonovy acid, 593 mg of sodium carbonate in 40 cm3water and 155 mg tetranitroaniline. Refluxed for 18 hours and the reaction medium is filtered through a porous glass filter with telicom. To the filtrate add 60 cm3ethyl acetate and 50 cm3of distilled water. The organic phase is washed with 2 times 20 cm3saturated aqueous solution of sodium chloride, then decanted and dried over magnesium sulfate. After filtration, the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC) and the residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45aboutC) get so 0.75 g of N-[5-(4-forfinal)-6-chloro-1-[[2-(trimethylsilyl)ethoxy]ethyl]-1H-indazol-3-yl]butanamide in the form of a yellow wax.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N)to 0.85 (t, J= 8 Hz, 2H), of 0.93 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), of 2.38 (t, J= 7 Hz, 2H), 3,55 (t, J= 8 Hz, 2H), 5,70 (s, 2H), 7,31 (t ush., J= 9 Hz, 2H), 7,46 (DD, J= 9 and 6 Hz, 2H), to $ 7.91 (s, 1H), 8,00 (s, 1H), or 10.60 (array, 1H).

Mass spectrum (EI): m/z = 461 M+;

m/z = 344 [M-OCH2CH2Si(CH3)3]+;

m/z = 333 [M-C6H12OSi]+.

N-[6-Chloro-5-(4-forfinal)-1H-indazol-3-yl]butanamide

To 0.73 g of N-[6-chloro-5-(4-forfinal)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 20 cm3tetrahydrofuran (THF) add 9.5 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 30 cm3ethyl acetate and the organic phase is washed successively with 2 times 20 cm3a saturated solution of sodium bicarbonate and 20 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC); the resulting crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled is, is evaporated under reduced pressure (2 kPa; 50aboutC) and dried (90 PA; 50aboutC)receiving 200 mg of N-[6-chloro-5-(4-forfinal)-1H-indazol-3-yl]butanamide in the form of a cream-colored powder.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,93 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), of 2.38 (t, J= 7 Hz, 2H), 7,30 (t ush., J= 9 Hz, 2H), 7,45 (DD ush., J= 9 and 6 Hz, 2H), 7,66 (s, 1H), a 7.85 (s, 1H), 10,46 (array, 1H), 12,80 (array, 1H).

Mass spectrum (EI): m/z = 331 M+;

m/z = 261 [M-C4H6O]+.

Example 73

N-[6-(4-AMINOPHENYL)-1H-indazol-3-yl]butanamide

To 0.85 grams of N-[6-(4-nitrophenyl)-1H-indazol-3-yl]butanamide described in example 64, 50 cm3acetic acid add 856 mg of powdered zinc, and then, 1 hour later, again add 856 mg of zinc and stirred for 1 hour at room temperature. The reaction medium is filtered through a porous glass filter with telicom and the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 100 cm3of tetrahydrofuran and 100 cm3ethyl acetate and the organic phase is washed successively with 100 cm3a saturated solution of sodium bicarbonate and 100 cm3a saturated solution of sodium chloride, then dried over magnesium sulfate, filtered and concentrated to dryness, receiving 500 mg of crude product which is purified by chromatography under pressure is Rhona 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with ethyl acetate. The fractions containing the desired product are pooled and solid proscout 20 cm3diethyl ether, filtered off, washed with 2 times 5 cm3diethyl ether, then dried (90 PA; 50aboutC)receiving 200 mg of N-[6-(4-AMINOPHENYL)-1H-indazol-3-yl]butanamide in the form of yellow crystals, melting at 230aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 5,24 (ush., 2H), 6,68 (l ush., J= 8 Hz, 2H), 7,27 (l ush,, J= 8.5 Hz, 1H), 7,42 (l ush., J= 8 Hz, 2H), 7,45 (ush., 1H), 7,76 (d, J= 8.5 Hz, 1H), 10,26 (array, 1H), 12,49 (ush., 1H).

Example 74

N-[6-[4-(Dimethylamino)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above in example 56, 50 cm3dioxane add 785 mg of 4-bromo-N,N-dimethylaniline, 646 mg of sodium carbonate, 10 cm3water and 196 mg tetranitroaniline. The medium is then refluxed for 18 hours, then held until it reaches again the room temperature and add 75 cm3ethyl acetate and 75 cm3water. The organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC)obtaining 1.6 g of crude product, which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 170 mg of N-[6-[4-(dimethylamino)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6), d in ppm: to 0.08 (s, N), from 0.84 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 2,98 (C, 6N), of 3.57 (t, J= 8 Hz, 2H), 5,71 (s, 2H), 6,85 (d, J= 9 Hz, 2H), 7,41 (l ush., J= 8.5 Hz, 1H), to 7.64 (d, J= 9 Hz, 2H), 7,82 (ush., 1H), a 7.85 (d, J= 8.5 Hz, 1H), 10,43 (array, 1H).

Mass spectrum (EI): m/z = 452 M+;

m/z = 335 [M-OCH2CH2Si(CH3)3]+;

m/z = 324 [M-C6H12OSi]+.

N-[6-[4-(Dimethylamino)phenyl]-1H-indazol-3-yl]butanamide

To 170 mg of N-[6-[4-(dimethylamino)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 10 cm3tetrahydrofuran (THF) added 2.3 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 50 cm3ethyl acetate and the organic phase is washed successively with 50 cm3a saturated solution of hydrocarbon the sodium and 50 cm 3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 160 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3diethyl ether, filtered and dried under reduced pressure (90 PA; 45aboutC)receiving 40 mg of N-[6-[4-(dimethylamino)phenyl]-1H-indazol-3-yl]butanamide in the form of yellow crystals, melting at 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t ush., J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 2,97 (C, 6N), 6,84 (l ush., J= 8.5 Hz, 2H), 7,31 (l ush., J= 9 Hz, 1H), 7,51 (ush., 1H), 7,58 (l ush., J= 8.5 Hz, 2H), 7,78 (d, J= 9 Hz, 1H), 10,27 (ush., 1H), to 12.52 ( ush., 1H).

Example 75

2-Chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide

To 5 g of 6-chloro-1H-indazol-3-amine in 300 cm3toluene added to 5.1 g of Chloroacetic anhydride acid and refluxed for 18 hours. The precipitation is filtered off, washed with 20 cm3toluene, then 20 cm 3dichloromethane and dried under reduced pressure (90 PA;45aboutC)receiving a 5.1 g of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide in the form of a gray powder, melting at 223aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 4.38 (s, 2H), 7,11 (DD, J= 9 and 1.5 Hz, 1H), 7,56 (ush., 1H), to 7.84 (d, J= 9 Hz, 1H), 10,87 (array, 1H), 12,96 (array, 1H).

N-(6-Chloro-1H-indazol-3-yl)-4-methyl-1-piperazineethanol

To 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide described above, in 15 cm3of dimethylformamide add 0.7 cm3N-methylpiperazine and heated at a temperature of 140aboutC for 2 hours, then the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC). Then add 50 cm3ethyl acetate and 50 cm3water and the organic phase is washed with 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness, obtaining of 0.53 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of dichloromethane, methanol and ammonium hydroxide (in a ratio of 93:7:1 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 5 cm3diethyl E. the Ira, filtered off and dried (90 PA; 45aboutC)receiving 192 mg of N-(6-chloro-1H-indazol-3-yl)-4-methyl-1-piperazinecarboxamide in the form of a powder beige color, melting at 165aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 2.18 (s, 3H), 2.40 a (array, 4H) 2,58 (array, 4H), up 3.22 (s, 2H), 7,09 (l ush., J= 9 Hz, 1H), 7,53 ( ush., 1H), 7,86 (d, J= 9 Hz, 1H), 10,11 (ush., 1H), 12,83 (ush., 1H).

Example 76

N-(6-Chloro-1H-indazol-3-yl)-1-piperidineacetate

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, and 0.61 cm3of piperidine. The reaction medium is refluxed for 2 hours, then precipitated precipitate is filtered off on a glass Frit and the crystals after treatment with methanol, purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 93:7 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 5 cm3diethyl ether, filtered and dried (90 PA; 45aboutC)receiving 447 mg of N-(6-chloro-1H-indazol-3-yl)-1-piperidineacetate in the form of a white powder, melting at 153aboutC.

1H-NMR spectrum (300 MHz, (CD 3)2SO-d6), d in ppm: to 1.42 (m, 2H), 1.57 in (m, 4H), 2,45-2,60 (m, 4H), 3,17 (s, 2H), was 7.08 (DD, J= 9 and 2 Hz, 1H), 7,52 (d, J= 2 Hz, 1H), 7,86 (d, J= 9 Hz, 1H), of 10.05 (ush., 1H), 12,82 (array, 1H).

Example 77

N-(6-Chloro-1H-indazol-3-yl)-4-morpholinoethyl

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, 0,54 cm3of the research. The reaction medium is refluxed for 2 hours, then concentrated to dryness under reduced pressure (2.7 kPa; 50aboutC) and the obtained crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with ethyl acetate. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC), then dried (90 PA; 45aboutC)receiving 470 mg of N-(6-chloro-1H-indazol-3-yl)-4-morpholinothio in the form of a white powder, melting at 82-90aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,58 (t ush., J= 4 Hz, 4H), 3,24 (s, 2H), 3,66 (t ush., J= 4 Hz, 4H), to 7.09 (DD, J= 9 and 2 Hz, 1H), 7,53 (d, J= 2 Hz, 1H), to 7.84 (d, J= 9 Hz, 1H), 10,18 (array, 1H), 12,83 (array ush., 1H).

Example 78

N-(6-Chloro-1H-indazol-3-yl)-1H-1,2,4-triazole-1-ndimethylacetamide

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, 423 mg 1,2,4-triaz the La, 283 mg of potassium carbonate. The reaction medium is refluxed for 4 hours, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the resulting crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with ethyl acetate. The fractions containing the desired product are pooled, evaporated under reduced pressure (2 kPa; 50aboutC) and dried (90 PA; 45aboutC)receiving 120 mg of N-(6-chloro-1H-indazol-3-yl)-1H-1,2,4-triazole-1-ndimethylacetamide in the form of a white powder, melting at above 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 5,27 (s, 2H) 7,10 (DD, J= 9 and 2 Hz, 1H), 7,55 (d, J= 2 Hz, 1H), to 7.84 (d, J= 9 Hz, 1H), 8,03 (s, 1H), at 8.60 (s, 1H), 11,00 (array, 1H), 12,90 (array, 1H).

Mass spectrum (DCI): m/z = 294 [M+NH4]+;

m/z = 277 [M+H]+.

Example 79

N-(6-Chloro-1H-indazol-3-yl)-2-(cyclohexylamino)ndimethylacetamide

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, 0.7 cm3cyclohexylamine. The reaction medium is refluxed for 2 hours, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the resulting crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40 to 60; diameter 2.5 cm), elwira a mixture of dichloromethane, methanol and ammonium hydroxide (in the ratio of 97:2,5:0,25 by volume). The fractions containing the desired product are pooled, and the residue is treated with 20 cm3di-isopropyl ether, filtered off, dried under reduced pressure (90 PA; 45aboutC)receiving 492 mg of N-(6-chloro-1H-indazol-3-yl)-2-(cyclohexylamino)ndimethylacetamide in the form of a white powder, melting at 170aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1,00-of 1.35 (m, 5H), and 1.56 (m, 4H), to 1.70 (m, 2H), 1,84 (d t ush., J= 12 Hz, 2H), 2,43 (m, 1H), 3,39 (s, 2H), to 7.09 (DD, J= 9 and 1.5 Hz, 1H), 7,52 (d, J= 1.5 Hz, 1H), to 7.93 (d, J= 9 Hz, 1H), 12,82 (array, 1H).

Example 80

2-[(Phenylmethyl)amino]-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, to 0.67 cm3benzylamine. The reaction medium is refluxed for 1 hour and the precipitated precipitate is filtered off, washed with 5 cm3acetonitrile and 5 cm3dichloromethane, then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of dichloromethane, methanol and ammonium hydroxide (in the ratio of 97:2,5:0,25 by volume). The fractions containing the desired product are pooled, and the remainder obrabatyvalis 20 cm 3diisopropyl ether, filtered off and dried under reduced pressure (90 PA; 45aboutC)receiving 305 mg of 2-[(phenylmethyl)amino]N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide in the form of a white powder, melting at 156aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 3,39 (s, 2H), 3,79 (s, 2H), to 7.09 (DD, J= 9 and 2 Hz, 1H), 7,26 (t ush., J= 7 Hz, 1H), 7,30 was 7.45 (m, 4H), 7,53 (d, J= 2 Hz, 1H), 7,89 (d, J= 9 Hz, 1H), 10,00-or 10.60 (array t ush., 1H), 12,82 (array, 1H).

Example 81

N-(6-Chloro-1H-indazol-3-yl)-1H-azepin-1-ndimethylacetamide

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, 0,69 cm3hexamethylenimine. The reaction medium is refluxed for 2 hours, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with ethyl acetate. The fractions containing the desired product are pooled and the residue is treated with 10 cm3diisopropyl ether, filtered off and dried under reduced pressure (90 PA; 45aboutC)receiving 670 mg of N-(6-chloro-1H-indazol-3-yl)-1H-azepin-1-ndimethylacetamide in the form of a hard yellow foam.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1,50-1,75 (m, 8H), 2,77 (t, J= 5 G is, 4H), to 3.36 (s, 2H), to 7.09 (DD, J= 9 and 2 Hz, 1H), 7,54 (d, J= 2 Hz, 1H), of 7.90 (d, J= 9 Hz, 1H), 10,06 (array, 1H), 12,50-13,20 (array ush., 1H).

Mass spectrum (EI): m/z = 306 M+.

Example 82

N-(6-Chloro-1H-indazol-3-yl)-1-piperazineethanol

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, 528 mg of piperazine. The reaction medium is refluxed for 1 hour, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of dichloromethane, methanol and ammonium hydroxide (in the ratio of 90:10:1 by volume). The fractions containing the desired product are pooled, concentrated under reduced pressure, then dried (90 PA; 45aboutC)receiving 380 mg of N-(6-chloro-1H-indazol-3-yl)-1-piperazineethanol in the form of a solid white foam.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2.49 USD (m, 4H), 2,77 (m, 4H), 3,19 (s, 2H), 7,10 (DD, J= 9 and 2 Hz, 1H), 7,55 (d, J= 2 Hz, 1H), 7,86 (d, J= 9 Hz, 1H), 10,10 (array, 1H).

Mass spectrum (EI): m/z = 293 M+;

m/z = 99 [C5H11N2]+.

Example 83

N-(6-Chloro-1H-indazol-3-yl)-2-[[3-(dimethylamino)propyl]-amino]ndimethylacetamide

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide is, 15 cm3acetonitrile, 0,77 cm33-(dimethylamino)Propylamine. The reaction medium is refluxed for 3 hours, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of dichloromethane, methanol and ammonium hydroxide (in the ratio of 90:10:1 by volume). The fractions containing the desired product are pooled, concentrated under reduced pressure, then dried (90 PA; 45aboutC)receiving 300 mg of N-(6-chloro-1H-indazol-3-yl)-2-[[3-(dimethylamino)propyl]amino]ndimethylacetamide in the form of a solid foam light brown color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 1.69 in (m, 2H), 2,11 (C, 6N), 2,28 (t, J= 7 Hz, 2H), 2,60 (t ush., J= 7 Hz, 2H), 3,35 (s, 2H), was 7.08 (DD, J= 9 and 2 Hz, 1H), 7,53 (d, J= 2 Hz, 1H), 7,89 (d, J= 9 Hz, 1H), 12,00-13,00 (array t ush., 1H).

Mass spectrum (EI): m/z = 309 M+.

Example 84

N-(6-Chloro-1H-indazol-3-yl)thiomorpholine-4-ndimethylacetamide

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, to 0.62 cm3thiomorpholine. The reaction medium is refluxed for 2 hours, the precipitated precipitate is filtered off and the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the crude product of imaut by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled, evaporated under reduced pressure (2 kPa; 50aboutC) and dried (90 PA; 45aboutC)receiving 560 mg of N-(6-chloro-1H-indazol-3-yl)thiomorpholine-4-ndimethylacetamide in the form of a solid foam blignault color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,70 (m, 4H), and 2.83 (m, 4H), of 3.27 (s, 2H), 7,10 (DD, J= 9 and 2 Hz, 1H), 7,54 (d, J= 2 Hz, 1H), 7,82 (d, J= 9 Hz, 1H), 10,16 (array, 1H), 12,60-13,10 (array ush., 1H).

Mass spectrum (EI): m/z = 310 M+;

m/z = 116 [C5H10NS]+.

Example 85

N-(6-Chloro-1H-indazol-3-yl)-1-pyrrolidineethanol

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, 0,51 cm3pyrrolidine. The reaction medium is refluxed for 2 hours, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the resulting crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira a mixture of dichloromethane, methanol and ammonium hydroxide (in the ratio 95:5:1 by volume). The fractions containing the desired product are pooled, evaporated under reduced pressure (2 kPa; 50aboutC) and dried (90 PA; 45aboutC)receiving 440 mg of N-(6-chloro-1H-indaz the l-3-yl)-1-pyrrolidineethanol in the form of powder off-white color, melting at 168aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 1.76 (m, 4H), of 2.64 (m, 4H), to 3.35 (s, 2H), to 7.09 (DD, J= 9 and 2 Hz, 1H), 7,53 (d, J= 2 Hz, 1H), to 7.84 (d, J= 9 Hz, 1H), 10,13 (array, 1H), 12,50-13,10 (array t ush., 1H).

Example 86

N-(6-Chloro-1H-indazol-3-yl)-2-[[2-(dimethylamino)ethyl]amino]-ndimethylacetamide

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, of 0.68 cm3N,N-dimethylethylenediamine. The reaction medium is refluxed for 2 hours, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira a mixture of dichloromethane, methanol and ammonium hydroxide (in the ratio 95:5:1 by volume). The fractions containing the desired product are pooled, concentrated under reduced pressure, then dried (90 PA; 45aboutC)receiving 113 mg of N-(6-chloro-1H-indazol-3-yl)-2-[[2-(dimethylamino)ethyl]amino]ndimethylacetamide in a solid white color, melting at 104aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 2,15 (C, 6N), was 2.34 (t, J= 6 Hz, 2H), 2,66 (t, J= 6 Hz, 2H), 3,40 (s, 2H), was 7.08 (DD ush., J= 9 and 2 Hz, 1H), 7,52 (ush., 1H), of 7.90 (d, J= 9 Hz, 1H), 9,50-10,30 (array t ush., 1H), 12,81 (array, 1H).

Example 87

N-(6-Chloro-1H-indazol-3-yl)-1-cyclopropanecarbonitrile

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide, 15 cm3acetonitrile, 0,45 cm3cyclopropylamine. The reaction medium is refluxed for 2 hours, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira with ethyl acetate. The fractions containing the desired product are pooled, concentrated under reduced pressure, receiving 300 mg still contaminated product, which is purified by high-performance liquid chromatography. After concentration of fractions containing the target product, and drying under reduced pressure (90 PA; 45about(C) obtain 140 mg of N-(6-chloro-1H-indazol-3-yl)-1-cyclopropanecarboxylate in the form of a white powder, melting at 218aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,70-0,95 (m, 4H), 2,82 (m, 4H), to 4.15 (s, 2H), 7,14 (DD ush., J= 9 and 2 Hz, 1H), 7,58 (ush., 1H), 7,86 (d, J= 9 Hz, 1H), 9,14 (array, 2H), 11,08 (array, 1H), 12,98 (ush., 1H).

Example 88

N-(6-Chloro-1H-indazol-3-yl)-2-(2-diethylaminoethylamine)ndimethylacetamide-ristritturato

Follow the procedure of example 75, from 500 mg of 2-chloro-N-(6-the ENT-1H-indazol-3-yl)acetamide", she 15 cm3acetonitrile, 0,86 cm3N,N-diethylethylenediamine. The reaction medium is refluxed for 2 hours, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the crude product is purified by high-performance liquid chromatography (Kromasil column; C8, 7 μm; a length of 350 mm, diameter 60 mm; eluting agent: a mixture of acetonitrile and water (in a ratio of 20:80 by volume)containing 0.1 % triperoxonane acid; flow rate: 125 cm3/min). The fractions containing the desired product are pooled, concentrated under reduced pressure (2 kPa; 50aboutC), then dried (90 PA; 45aboutC)receiving 870 mg of N-(6-chloro-1H-indazol-3-yl)-2-(2-diethylaminoethylamine)ndimethylacetamide-Tris-trifenatate in a solid white color, melting at 160aboutC.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6with the addition of a few drops CD3COOD-d4at a temperature of 363 K), d in ppm: 1,24 (t, J= 7.5 Hz, 6N), 3,23 (kV, J= 7.5 Hz, 4H), 3,47 (m, 4H), to 4.16 (s, 2H), 7,12 (l ush., J= 8.5 Hz, 1H), 7,58 (ush., 1H), 7,87 (d, J= 8.5 Hz, 1H).

Example 89

N-[5,6-Diphenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[5,6-dibromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 70, 150 cm3dioxane is added 1.12 g phenylboronic acid, 1.55 g of sodium carbonate in 40 cm3 water, 463 mg tetranitroaniline and refluxed for 18 hours. The reaction medium is diluted with 100 cm3ethyl acetate and 100 cm3water, then the reaction medium is filtered through a porous glass filter with telicom. The organic phase is decanted and washed with 75 cm3saturated aqueous solution of sodium chloride, decanted, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC)obtaining 2.6 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC), then dried (90 PA; 45aboutC)receiving 1.4 g of N-[5,6-diphenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,06 (s, N), 0,86 (t, J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,42 (t ush., J= 7 Hz, 2H)and 3.59 (t, J= 8 Hz, 2H), 5,74 (s, 2H), 7,05-to 7.35 (m, 10H), 7,71 (s, 1H), 7,89 (s, 1H), 10,57 (array, 1H).

Mass spectrum (EI): m/z = 485 M+;

m/z = 368 [M-OCH2CH2Si(CH3)3]+;

m/z = 357 [M-C6H12OSi]+.

N-[5,6-Diphenyl)-1H-shall indazol-3-yl]butanamide

To 1.5 g of N-[5,6-diphenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 40 cm3tetrahydrofuran (THF) add 17,2 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 75 cm3ethyl acetate and the organic phase is washed with 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 1.5 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); else contaminated product was then purified by high-performance liquid chromatography (column Hypersil; C18, 5 μm; length 250 mm, diameter 21 mm; eluting agent: a mixture of methanol and water (in the ratio of 70:30 by volume)containing 0.1 % triperoxonane acid; flow rate: 10 cm3/min); obtained by concentration to dryness of fractions containing the target product, the residue is treated with 10 cm3diisopropyl ether, ochiltree is up, washed 2 times for 5 cm3diisopropyl ether and dried (90 PA; 45aboutC)receiving 100 mg of N-[5,6-diphenyl-1H-indazol-3-yl]butanamide in the form of white crystals, melting at 210aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 7,00-7,30 (m, 10H), 7,40 (s, 1H), 7,82 (s, 1H), 10,43 (ush., 1H), was 12.75 (array, 1H).

Example 90

N-[6-Chloro-5-(4-were)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

Follow the procedure of example 62; to 1 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 58, 50 cm3dioxane add 456 mg 4-methylphenylacetic acid, 560 mg of sodium carbonate, 20 cm3distilled water and 155 mg tetranitroaniline. Refluxed for 90 minutes, then held until it reaches again the temperature of 20aboutS, after which the reaction medium is filtered through a porous glass filter with telicom and to the filtrate add 60 cm3ethyl acetate. Desantirovaniya the organic phase is washed with 30 cm3saturated aqueous solution of sodium chloride, then dried over magnesium sulfate. After filtration, the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC) and the residue is purified by chromatography under a pressure of the argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) obtain 880 mg of N-[6-chloro-5-(4-were)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of powder off-white color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N)to 0.85 (t, J= 8 Hz, 2H), of 0.93 (t, J= 7.5 Hz, 3H), of 1.64 (m, 2H), 2,39 (s, 3H), 2,39 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), 5,70 (s, 2H), 7,30 (m, 4H), 7,87 (s, 1H), 7,99 (, 1H), 10,59 (array, 1H).

Mass spectrum (EI): m/z = 457 M+;

m/z = 340 [M-OCH2CH2Si(CH3)3]+;

m/z = 329 [M-C6H12OSi]+.

N-[6-chloro-5-(4-were)-1H-indazol-3-yl]butanamide

To 870 mg of N-[6-chloro-5-(4-were)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 20 cm3tetrahydrofuran (THF) add 11,4 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The medium is then refluxed for 20 hours, and then held until it reaches again the room temperature and add 20 cm3ethyl acetate; the organic phase is washed with 2 times 20 cm3saturated aqueous sodium hydrogen carbonate solution, and then 2 times with 20 cm3saturated aqueous solution of chlorine is IDA sodium. The organic phase is decanted, dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 10 cm3diethyl ether, filtered off on a glass Frit and then dried under reduced pressure (90 PA; 50aboutC)receiving 195 mg of N-[6-chloro-5-(4-were)-1H-indazol-3-yl]butanamide in the form of a powder beige color.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6), d in ppm: 0,93 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), 2,30-of 2.50 (m, 2H), of 2.38 (s, 3H), 7,28 (m, 4H), to 7.64 (s, 1H), 7,81 (s, 1H), 10,45 (array, 1H).

Mass spectrum (EI): m/z = 327 M+;

m/z = 257 [M-C4H6O]+.

Example 91

N-[6-[4-(Phenylmethoxy)phenyl]-5-phenyl-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to example 63, 100 cm3dioxane add 306 mg of phenylboronic acid, 427 mg of sodium carbonate in 30 cm3water, 248 mg tetranitroaniline and refluxed for 18 hours. To the reaction medium, add 100 cm3ethyl acetate, 100 cm3water and the reaction medium is filtered through a porous glass filter with telicom. The organic phase is decanted, washed sequentially with 100 cm3water and 100 cm3 a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC)receiving 2.5 g of oil, which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 1 g of N-[6-[4-(phenylmethoxy)phenyl]-5-phenyl-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,06 (s, N), from 0.84 (t, J= 8 Hz, 2H), were 0.94 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), 2.40 a (t ush., J= 7 Hz, 2H), only 3.57 (t, J= 8 Hz, 2H), 5,09 (s, 2H), 5,71 (s, 2H), 6,92 (d, J= 8.5 Hz, 2H), 7,00-of 7.55 (m, 10H), was 7.08 (d, J= 8.5 Hz, 2H), 7,66 (s, 1H), a 7.85 (s, 1H), 10,54 (array, 1H).

Mass spectrum (EI): m/z = 591 M+;

m/z = 474 [M-OCH2CH2Si(CH3)3]+.

N-[5-Phenyl-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-[4-(phenylmethoxy)phenyl]-5-phenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 40 cm3tetrahydrofuran (THF) add 10.1 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 75 cm3 3a saturated solution of sodium bicarbonate and 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 2 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is dried (90 PA; 45aboutC)receiving 650 mg of N-[5-phenyl-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm as 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), to 5.08 (s, 2H), 6,91 (d, J= 8.5 Hz, 2H), 7,05-of 7.55 (m, 10H), to 7.09 (d, J= 8.5 Hz, 2H), was 7.36 (s, 1H), 7,80 (s, 1H), 10,42 (ush., 1H), 12,70 (ush., 1H).

Mass spectrum (EI): m/z = 461 M+;

m/z = 391 [M-C4H6O]+;

m/z = 300 [391-C6H5CH2]+.

N-[5-Phenyl-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide

To 650 mg of N-[5-phenyl-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide obtained above, add 10 cm3trimethylsilylmethyl and refluxed for 3 hours. On Wednesday add 3 cm3methanol and food is destroying boiling under reflux for 15 minutes, then the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 75 cm3ethyl acetate and washed with 2 times 50 cm310%sodium thiosulfate solution, then with 50 cm3water and 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure, gaining 0.6 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3diisopropyl ether, filtered off, washed with 5 cm3ethyl acetate and 5 cm3diethyl ether, then dried (90 PA; 45aboutC)receiving 200 mg of N-[5-phenyl-6-(4-(hydroxyphenyl)-1H-indazol-3-yl]butanamide, melting at 220aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), of 2.38 (t, J= 7 Hz, 2H), 6,63 (d, J= 8 Hz, 2H), 6,94 (d, J= 8 Hz, 2H), 7,09 (l ush., J= 7.5 Hz, 2H), 7,15-7,30 (m, 3H), 7,33 (s, 1H), to 7.77 (s, 1H), 9,40 (array, 1H) the 10.40 (ush., 1H), 12,67 (array, 1H).

Example 92

N-[6-Chloro-5-(4,4,55-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 7.5 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described in example 58, 225 cm3dioxane type of 5.11 g of bis(pinacolato)DIBORANE, 277 mg of bis(dibenzylideneacetone)palladium, then 2,48 g of potassium acetate and finally, 330 mg of tricyclohexylphosphine. The medium is refluxed for 18 hours, then held until it reaches again the room temperature and add 100 cm3ethyl acetate and 100 cm3water. The organic phase is decanted, washed with 100 cm3water, 100 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2 kPa; 45aboutC)receiving 11.2 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 6,16 g of N-[6-chloro-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of an orange oil. The product is used in the form in which it was received.

N-[6-Chloro-5-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 2 g of N-[6-chloro-5-(4,,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, as described above, 100 cm3dioxane is added 246 mg of 4-bromonitromethane, 1.2 g of sodium carbonate in 20 cm3water and 365 mg tetranitroaniline. The medium is then refluxed for 20 hours, and then held until it reaches again the room temperature and add 100 cm3ethyl acetate and 100 cm3water. The reaction medium is filtered through a porous glass filter with telicom, the organic phase is decanted, washed with 100 cm3water, 100 cm3saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The crude residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio of 85:15 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 690 mg of N-[6-chloro-5-(4-nitrophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of yellow crystals.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N)to 0.85 (t, J= 8 Hz, 2H), to 0.92 (t, J= 7.5 Hz, 3H), of 1.62 (m, 2H), 2,39 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), 5,72 (s, 2H) 7,74 (d, J= 8.5 Hz, 2H), 8,01 (s, 1H), of 8.09 (s, 1H), 8,35 (d, J= 8.5 Hz, 2H), 10,70 (array, 1H).

Mass-Spa is Tr (EI): m/z = 488 M +;

m/z = 371 [M-OCH2CH2Si(CH3)3]+;

m/z = 360 [M-C6H12OSi]+;

m/z = 73 [Si(CH3)3]+.

N-[6-Chloro-5-(4-nitrophenyl)-1H-indazol-3-yl]butanamide

To 3 g of N-[6-chloro-5-(4-nitrophenyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 135 cm3tetrahydrofuran (THF) add 36.8 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran, then the medium is refluxed for 18 hours, and then held until it reaches again the room temperature and add 100 cm3ethyl acetate and 75 cm3saturated aqueous solution of sodium bicarbonate. The organic phase is decanted, washed with 100 cm3saturated aqueous sodium hydrogen carbonate solution, then with 100 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and concentrated to dryness under reduced pressure (2 kPa; 50aboutC); the residue is treated with 35 cm3diisopropyl EPE is a, filtered off on a glass Frit and then washed successively with 2 times 20 cm3diisopropyl ether. After drying (90 PA; 50about(C) obtain 88 mg of N-[6-chloro-5-(4-nitrophenyl)-1H-indazol-3-yl]butanamide in the form of yellow crystals, melting at 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.92 (t, J= 7.5 Hz, 3H), of 1.62 (m, 2H), 2,37 (t, J= 7 Hz, 2H), 7,73 (d, J= 8 Hz, 2H), 7,72 (s, 1H), of 7.96 (s, 1H), 8.34 per (d, J= 8 Hz, 2H), of 10.58 (ush., 1H), 12,50-13,20 (array t ush., 1H).

Example 93

N-[5-(4-AMINOPHENYL)-6-chloro-1H-indazol-3-yl]butanamide

To 0,93 g of N-[6-chloro-5-(4-nitrophenyl)-1H-indazol-3-yl]-butanamide described above, in 50 cm3acetic acid add 845 mg of powdered zinc, and then, 1 hour later, again add 845 mg of zinc; the reaction medium is filtered through a porous glass filter with telicom and the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 100 cm3ethyl acetate and 75 cm3water and the organic phase is decanted, washed sequentially with 75 cm3water and 50 cm3a saturated solution of sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated to dryness, obtaining 480 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (granulo Atria 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and solid proscout 10 cm3diethyl ether, filtered off, washed with 2 times 5 cm3diethyl ether, then dried (90 PA; 50aboutC)receiving 110 mg of N-[5-(4-AMINOPHENYL)-6-chloro-1H-indazol-3-yl]butanamide in the form of a solid buff.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.92 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), a 2.36 (t, J= 7 Hz, 2H), total of 5.21 (array, 2H), 6,63 (d, J= 8 Hz, 2H), 7,06 (d, J= 8 Hz, 2H), 7,58 (s, 1H), 7,72 (s, 1H), 10,42 (ush., 1H), 12,71 (array, 1H).

Mass spectrum (EI): m/z = 328 M+;

m/z = 284 [M-C3H6]+;

m/z = 258 [M-C4H6O]+.

Example 94

N-[6-Chloro-5-(4-ethylphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 58, 75 cm3dioxane add 504 mg 4-ethylvinylbenzene acid, 664 mg of sodium carbonate in 20 cm3distilled water and 202 mg tetranitroaniline. Refluxed for 18 hours, then held until it reaches again the room temperature and add 75 cm3ethyl acetate and 50 cm3water and the reaction medium is filtered through a porous glass the nd filter telicom. The filtrate is decanted and the organic phase is washed successively with 50 cm3water, 500 cm3saturated aqueous solution of sodium chloride, decanted, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC), then dried (90 PA; 50aboutC)obtaining 1.1 g of N-[6-chloro-5-(4-ethylphenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N)to 0.85 (t, J= 8 Hz, 2H), of 0.93 (t, J= 7.5 Hz, 3H), of 1.26 (t, J= 7.5 Hz, 3H), of 1.64 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 2,69 (kV, J= 7.5 Hz, 2H), 3,55 (t, J= 8 Hz, 2H), 5,70 (s, 2H), 7,33 (m, 4H), 7,89 (s, 1H), 8,00 (s, 1H), at 10.64 (array, 1H).

Mass spectrum (EI): m/z = 471 M+;

m/z = 354 [M-OCH2CH2Si(CH3)3]+;

m/z = 343 [M-C6H12OSi]+.

N-[6-Chloro-5-(4-ethylphenyl)-1H-indazol-3-yl]butanamide

To 1.1 g of N-[6-chloro-5-(4-ethylphenyl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above (party R-31335-046-2), 50 cm3tetrahydrofuran (THF) added 14 the m 3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The medium is then refluxed for 18 hours, and then held until it reaches again the room temperature and add 75 cm3ethyl acetate; the organic phase is washed with 2 times 100 cm3saturated aqueous solution of sodium bicarbonate, then with 75 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutTo the residue is treated with 20 cm3diisopropyl ether, filtered off on a glass Frit and washed with 2 times 10 cm3diisopropyl ether. After drying under reduced pressure (90 PA; 50about(C) obtain 440 mg of N-[6-chloro-5-(4-ethylphenyl)-1H-indazol-3-yl]butanamide in the form of white crystals, melting at 240aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.92 (t, J= 7.5 Hz, 3H), 1,24 (t, J= 7.5 Hz, 3H, of 1.62 (m, 2H), 2,37 (t, J= 7 Hz, 2H), to 2.67 (q, J= 7.5 Hz, 2H), 7,31 (m, 4H), to 7.64 (s, 1H), 7,82 (s, 1H), 10,48 (array, 1H), 12,80 (array, 1H).

Example 95

N-[6-Chloro-5-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 2 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 58, 100 cm3dioxane is added 1.54 g of 4-benzyloxyaniline acid, 1,32 g of sodium carbonate in 20 cm3water and 404 mg tetranitroaniline. Refluxed for 18 hours, then held until it reaches again the room temperature and add 75 cm3ethyl acetate and 50 cm3water and the reaction medium is filtered through a porous glass filter with telicom. The filtrate is decanted and the organic phase is washed successively with 100 cm3water, then 75 cm3saturated aqueous solution of sodium chloride, decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the remainder of obrabecim the Ute with 50 cm 3cyclohexane, filtered off, washed with 2 times 25 cm3cyclohexane and dried under reduced pressure (90 PA; 50aboutC)receiving of 2.35 g of N-[6-chloro-5-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of white crystals, melting at 130aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,06 (s, N), from 0.84 (t, J= 8 Hz, 2H), to 0.92 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), of 2.38 (t, J= 7 Hz, 2H), 3,54 (t, J= 8 Hz, 2H), by 5.18 (s, 2H), 5,69 (s, 2H), 7,11 (d, J= 8.5 Hz, 2H), 7,30 one-7,55 (m, 5H), 7,35 (d, J= 8.5 Hz, 2H), 7,86 (s, 1H), 7,98 (s, 1H), 10,61 (array, 1H).

N-[6-Chloro-5-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

To 1.1 g of N-[6-chloro-5-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 50 cm3tetrahydrofuran (THF) add 25,1 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The medium is then refluxed for 18 hours, and then held until it reaches again the room temperature and add 100 cm3ethyl acetate; the organic phase is washed with 2 times 100 cm3saturated aqueous sodium hydrogen carbonate solution, then with 100 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure (2 kPa; 4 aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 30 cm3diisopropyl ether, filtered off on a glass Frit and washed 2 times with 20 cm3diisopropyl ether. After drying under reduced pressure (90 PA; 50about(C) obtain 1.3 g of N-[6-chloro-5-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of white crystals, melting at 230aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,93 (t, J= 7.5 Hz, 3H), and 1.63 (m, 2H), 2,37 (t, J= 7 Hz, 2H), by 5.18 (s, 2H), 7,11 (d, J= 8.5 Hz, 2H), 7,35 (d, J= 8.5 Hz, 2H), 7,37 (m, 1H), 7,44 (t ush., J= 7.5 Hz, 2H), 7,51 (l ush., J= 7.5 Hz, 2H), to 7.64 (s, 1H), 7,81 (s, 1H), 10,48 (ush., 1H), 12,80 (array, 1H).

Example 96

N-[6-Chloro-5-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide

To 1.1 g of N-[6-chloro-5-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide obtained according to example 95, add 20 cm3trimethylsilylmethyl and refluxed for 18 hours. On Wednesday add 3 cm3methanol and continue boiling under reflux for 30 minutes, then the reaction is ionic environment concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 100 cm3ethyl acetate and 100 cm3water and the organic phase is washed 2 times with 75 cm310%sodium thiosulfate solution, then using a 70 cm3water and 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure, getting 1.44 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 20 cm3diisopropyl ether, filtered off, washed 3 times in 10 cm3diisopropyl ether, then dried (90 PA; 45aboutC)receiving 210 mg of N-[6-chloro-5-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of white powder.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 0.92 (t, J= 7.5 Hz, 3H), of 1.62 (m, 2H), 2,37 (t, J= 7 Hz, 2H), at 6.84 (d, J= 8.5 Hz, 2H), 7,21 (d, J= 8.5 Hz, 2H), to 7.61 (s, 1H), to 7.77 (s, 1H), to 9.57 (array, 1H), 10,45 (ush., 1H), 12,76 (array, 1H).

Mass spectrum (EI): m/z = 329 M+;

m/z = 259 [M-C4H6O]+.

Example 97

N-[5,6-bis[4-(phenylmethoxy)phenyl]-1-[[2-(t is Immission)-ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1.35 g of N-[5,6-dibromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described in example 70, 100 cm3dioxane is added to 1.9 g of 4-benzyloxyaniline acid, 1.63 g of sodium carbonate in 20 cm3distilled water and 500 mg tetranitroaniline. Refluxed for 18 hours, then held until it reaches again the room temperature and add 100 cm3ethyl acetate and 100 cm3water and the reaction medium is filtered through a porous glass filter with telicom. The organic phase is decanted, washed with 100 cm3saturated aqueous solution of sodium chloride, decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled, evaporated under reduced pressure (2 kPa; 50aboutC) and dried (90 PA; 50aboutC)receiving a 1.96 g of N-[5,6-bis[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide in the form of an orange oil 70%purity, used by tel Quel in the following experience.

1H-NMR spectrum (300 MHz, (CD3)2/sub> SO-d6), d in ppm: - 0,06 (s, N)to 0.85 (t, J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,41 (t ush., J= 7 Hz, 2H), only 3.57 (t, J= 8 Hz, 2H), 5,10 (m, 4H), 5,71 (ush., 2H), 6.90 to-7,00 (m, 4H),? 7.04 baby mortality (d, J= 8.5 Hz, 2H), 7,11 (d, J= 8.5 Hz, 2H), 7,30-of 7.55 (m, 10H), to 7.64 (s, 1H), 7,81 (s, 1H), 10,55 (array, 1H).

Mass spectrum (EI): m/z = 697 M+;

m/z = 580 [M-OCH2CH2Si(CH3)3]+;

m/z = 91 [C6H5CH2]+.

N-[5,6-bis[4-(Phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide

To 1.9 g of N-[5,6-bis[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, 100 cm3tetrahydrofuran (THF) add 16,3 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The medium is then refluxed for 18 hours, and then held until it reaches again the room temperature and add 100 cm3ethyl acetate; the organic phase is washed with 2 times 100 cm3saturated aqueous sodium hydrogen carbonate solution, then with 100 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). F. the shares, containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 25 cm3diisopropyl ether, filtered off on a glass Frit and washed 2 times with 20 cm3diisopropyl ether. After drying under reduced pressure (90 PA; 50aboutC) get 700 mg of N-[5,6-bis[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of white crystals, melting at 140aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 5,08 (ush., 4H), 6,85-7,00 (m, 4H), 7,01 (d, J= 9 Hz, 2H), to 7.09 (d, J= 9 Hz, 2H), 7,30-of 7.55 (m, 10H), 7,33 (s, 1H), 7,74 (s, 1H), accounted for 10.39 (ush., 1H), 12,67 (ush., 1H).

Example 98

N-[5,6-bis(4-Hydroxyphenyl)-1H-indazol-3-yl]butanamide

To 700 mg of N-[5,6-bis[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide obtained according to example 97, add 10 cm3trimethylsilylmethyl and refluxed for 18 hours. In medium was added 30 cm3methanol and continue boiling under reflux for 15 minutes, then the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 75 cm3ethyl acetate and the organic phase is washed 2 times with 75 cm310%sodium thiosulfate solution, then through the th 75 cm 3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 900 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 20 cm3diisopropyl ether, filtered off, washed with 3 cm3ethyl acetate, then 2 x 10 cm3diisopropyl ether and dried (90 PA; 45aboutC)receiving 220 mg of N-[5,6-bis(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of a white powder, melting at 180aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), of 2.38 (t, J= 7 Hz, 2H), 6,55-6,70 (m, 4H), 6,86 (d, J= 9 Hz, 2H), 6,94 (d, J= 9 Hz, 2H), 7,28 (s, 1H), 7,68 (s, 1H), 9,34 (array, 2H), 10,36 (ush., 1H), 12,60 (array, 1H).

Example 99

N-[5-(3-Furanyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1,25 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to the prima is 63, 125 cm3dioxane add 353 mg 3-Puilboreau acid, 624 mg of sodium carbonate in 25 cm3water, 311 mg tetranitroaniline and refluxed for 18 hours. To the reaction medium, add 100 cm3ethyl acetate and 75 cm3water and the reaction medium is filtered through a porous glass filter with telicom. The organic phase is decanted, washed sequentially with 75 cm3water and 75 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC)obtaining 2.6 g of oil, which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 1 g of N-[5-(3-furanyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of cream-coloured crystals.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,07 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,42 (t, J= 7 Hz, 2H), 3,55 (t, J= 8 Hz, 2H), further 5.15 (s, 2H), of 5.68 (s, 2H), 6,07 (m, 1H),? 7.04 baby mortality (d, J= 8.5 Hz, 2H), 7,19 (d, J= 8.5 Hz, 2H), 7,30-of 7.55 (m, 6N), 7,55 (t, J= 2 Hz, 1H), to 7.61 (s, 1H), to $ 7.91 (s, 1H), 10,53 (array, 1H).

Mass when ECTR (EI): m/z = 581 M +;

m/z = 464 [M-OCH2CH2Si(CH3)3]+.

N-[5-(3-Furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide

To 1 g of N-[5-(3-furanyl)6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 75 cm3tetrahydrofuran (THF) add 10,3 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 75 cm3ethyl acetate and the organic phase is washed successively with 100 cm3a saturated solution of sodium bicarbonate and 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 1.4 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is dried (90 PA; 45aboutC)receiving 530 mg of N-[5-(3-furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d is ppm: 0,98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,41 (t, J= 7 Hz, 2H), further 5.15 (s, 2H), 6,07 (ush., 1H), 7,02 (d, J= 8.5 Hz, 2H), 7,20 (d, J= 8.5 Hz, 2H), 7,30-of 7.60 (m, 6N), 7,31 (s, 2H), 7,86 (s, 1H), 10,36 (array, 1H), 12,66 (array, 1H).

Mass spectrum (EI): m/z = 451 M+;

m/z = 381 [M-C4H6O]+.

N-[5-(3-Furanyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide

To 500 mg of N-[5-(3-furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide described above, add 10 cm3trimethylsilylmethyl and refluxed for 18 hours. In medium was added to 25 cm3methanol and continue boiling under reflux for 10 minutes, then the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 75 cm3ethyl acetate and 50 cm3of tetrahydrofuran, and then the organic phase is washed with 2 times 100 cm310%-aqueous solution of sodium thiosulfate, then with 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure, getting 950 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and Privat under reduced pressure (2 kPa; 50aboutC); the residue is treated with 5 cm3ethyl acetate, filtered off, washed with 1 cm3ethyl acetate, then 20 cm3diethyl ether and dried (90 PA; 45aboutC)receiving 10 mg of N-[5-(3-furanyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of a white powder, melting at 185aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 6,07 (ush., 1H), 6.75 in (d, J= 8.5 Hz, 2H), 7,06 (d, J= 8.5 Hz, 2H), 7,27 (ush., 2H), 7,52 (m, 1H), 7,83 (s, 1H), 9,40-9,65 (array, 1H), 10,33 (array, 1H), 12,50-was 12.75 (array, 1H).

Mass spectrum (DCI): m/z = 362 [M+H]+.

Example 100

N-[5-(4-Ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to example 63, 100 cm3dioxane add 379 mg 4-ethylvinylbenzene acid, 428 mg of sodium carbonate in 30 cm3water, 259 mg tetranitroaniline and refluxed for 18 hours. To the reaction medium, add 100 cm3ethyl acetate and 100 cm3water and the reaction medium is filtered through a porous glass filter with telicom. The organic phase is decanted, washed sequentially with 75 cm3water and 75 cm3n is casinogo solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC)obtaining 1.7 g of oil, which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 850 mg of N-[5-(4-ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of crystals of gray.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,07 (s, N), from 0.84 (t, J= 8 Hz, 2H), were 0.94 (t, J= 7.5 Hz, 3H), of 1.18 (t, J= 7,5 Hz, 3H), of 1.65 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 2,58 (kV, J= 7.5 Hz, 2H), only 3.57 (t, J= 8 Hz, 2H), 5,10 (s, 2H), 5,70 (s, 2H), 6,93 (d, J= 8.5 Hz, 2H), 7,02 (d, J= 8.5 Hz, 2H), to 7.09 (d, J= 8.5 Hz, 2H), 7,11 (d, J= 8.5 Hz, 2H), 7,30-to 7.50 (m, 5H), 7,63 (s, 1H), 7,82 (s, 1H), 10,50 (array, 1H).

Mass spectrum (EI): m/z = 619 M+;

m/z = 502 [M-OCH2CH2Si(CH3)3]+;

m/z = 91 [C6H5CH2]+.

N-[5-(4-Ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide

To 850 mg of N-[5-(4-ethylphenyl)6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 50 cm3tetrahydrofuran (THF) type 8.3 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran the e and refluxed for 18 hours; after cooling, add 75 cm3ethyl acetate and the organic phase is washed successively with 2 times 100 cm3a saturated solution of sodium bicarbonate and with 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 1.5 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is dried (90 PA; 45aboutC)receiving 660 mg of N-[5-(4-ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of crystals of gray.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.17 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 2,58 (kV, J= 7.5 Hz, 2H), to 5.08 (s, 2H), make 6.90 (d, J= 8.5 Hz, 2H), 7,00 (d, J= 8.5 Hz, 2H), was 7.08 (d, J= 8,5 Hz, 4H), 7,30-to 7.50 (m, 5H), 7,34 (s, 1H), 7,76 (s, 1H), 10,36 (array, 1H), 12,66 (array, 1H).

Mass spectrum (EI): m/z = 489 M+;

m/z = 419 [M-C4H6O]+.

N-[5-(4-Ethylphenyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]-butanamide

To 600 mg of N-[5-(4-ethylphenyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide described the data above, add 10 cm3trimethylsilylmethyl and refluxed for 18 hours. In medium was added 30 cm3methanol and continue boiling under reflux for 5 minutes, then the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 100 cm3ethyl acetate and the organic phase is washed with 2 times 100 cm310%-aqueous solution of sodium thiosulfate, then with 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure, getting 650 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 15 cm3diisopropyl ether, filtered off, washed with 5 cm3ethyl acetate, then 10 cm3diisopropyl ether and dried (90 PA; 45aboutC)receiving 180 mg of N-[5-(4-ethylphenyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of cream-coloured crystals, melting at 225aboutC.

H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.17 (t, J= 7.5 Hz, 3H), of 1.65 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 2,58 (kV, J= 7.5 Hz, 2H), 6,63 (d, J= 8.5 Hz, 2H), 6,95 (d, J= 8.5 Hz, 2H), 7,00 (d, J= 8.5 Hz, 2H), 7,08 (d, J= 8.5 Hz, 2H), 7,31 (s, 1H), 7,74 (s, 1H), 9,36 (array, 1H), 10,35 (ush., 1H), 12,61 (array, 1H).

Example 101

N-[5-(3-Pyridinyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to example 63, 100 cm3dioxane add 371 mg 3 pyridylmethylamine, 428 mg of sodium carbonate in 30 cm3water, 258 mg tetranitroaniline and refluxed for 18 hours. To the reaction medium, add 100 cm3ethyl acetate, 100 cm3water and the reaction medium is filtered through a porous glass filter with telicom. The organic phase is decanted, washed sequentially with 75 cm3water and 75 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC)obtaining 1.6 g of oil, which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). Fraction, the content is the following target product, combined and evaporated under reduced pressure (2 kPa; 50about(C)receiving 700 mg of N-[5-(3-pyridinyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N)to 0.85 (t, J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,42 (t, J= 7 Hz, 2H), to 3.58 (t, J= 8 Hz, 2H), 5,11 (s, 2H), 5,73 (s, 2H), of 6.96 (d, J= 8.5 Hz, 2H), 7,10 (d, J= 8.5 Hz, 2H), 7,30-of 7.55 (m, 5H), 7,31 (DD ush., J= 7.5 and 5 Hz, 1H), 7,50 (DDD, J= 7.5 to 2.5 and 2 Hz, 1H), 7,72 (s, 1H), 7,92 (s, 1H), 8,31 (l ush., J= 2.5 Hz, 1H), 8,43 (DD, J= 5 and 2 Hz, 1H), 10,57 (array, 1H).

Mass spectrum (EI): m/z = 592 M+;

m/z = 475 [M-OCH2CH2Si(CH3)3]+;

m/z = 91 [C6H5CH2]+.

N-[5-(3-Pyridinyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide

To 700 mg of N-[5-(3-pyridinyl)6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 50 cm3tetrahydrofuran (THF) add 7.1 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 75 cm3ethyl acetate and the organic phase is washed successively with 2 times by 75 cm3a saturated solution of sodium bicarbonate, then with the help of 59 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over su is hatom magnesium, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 850 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is dried (90 PA; 45aboutC)receiving 460 mg of N-[5-(3-pyridinyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of cream-coloured crystals.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), to 5.08 (s, 2H), 6,93 (d, J= 8.5 Hz, 2H), to 7.09 (d, J= 8.5 Hz, 2H), 7,29 (DD ush., J= 7.5 and 4.5 Hz, 1H), 7,30-of 7.55 (m, 6N), 7,40 (s, 1H), 7,86 (s, 1H), 8,28 (l ush., J= 2 Hz, 1H), to 8.41 (DD, J= 4.5 and 2 Hz, 1H), 10,42 (array, 1H), 12,76 (array, 1H).

Mass spectrum (EI): m/z = 462 M+;

m/z = 392 [M-C4H6O]+.

N-[5-(3-Pyridinyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]-butanamide

To 460 mg of N-[5-(3-pyridinyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide described above, add 10 cm3trimethylsilylmethyl and refluxed for 18 hours. The insoluble part is filtered off, washed 2 times with 20 cm3diethyl ether and treated with 50 cm3tetrahydrofuran (THF, 25 cm3these are the acetate and the organic phase is washed with 2 times 100 cm 310%sodium thiosulfate solution, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure, receiving 330 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3diisopropyl ether, filtered off, washed 3 times for 5 cm3diisopropyl ether, then with 5 cm3ethyl acetate, then with 10 cm3diisopropyl ether and dried (90 PA; 45aboutC)receiving 90 mg of N-[5-(3-pyridinyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]-butanamide in the form of cream-coloured crystals, melting at 165aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm as 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 6,66 (d, J= 8.5 Hz, 2H), of 6.96 (d, J= 8.5 Hz, 2H), 7,30 (DD, J= 7.5 and 4.5 Hz, 1H), 7,38 (s, 1H), 7,49 (dt, J= 7.5 and 2 Hz, 1H), 7,85 (s, 1H), 8,28 (d, J= 2 Hz, 1H), to 8.41 (DD, J= 4.5 and 2 Hz, 1H), 9,46 (array, 1H), 10,45 (array, 1H), 12,74 (array, 1H).

Example 102

N-[5-(2-Furanyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1,25 g of N-[5-bromo-6-[4-(phenylmethoxy)phenyl]-1[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, obtained according to example 63, 125 cm3dioxane add 353 mg 2-Puilboreau acid, 624 mg of sodium carbonate in 25 cm3water, 311 mg tetranitroaniline and refluxed for 18 hours, then add 611 mg of 2-furan-2-yl-4,4,5,5-tetramethyl[1,3,2]dioxaborolane and continue boiling under reflux for 4 hours. To the reaction mixture is added 75 cm3ethyl acetate and 75 cm3water and the reaction medium is filtered through a porous glass filter with telicom. The organic phase is decanted, washed with 75 cm3water, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC)receiving 2 g of oil, which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 75:25 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 1.20 g of N-[5-(2-furanyl)-6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in a solid beige color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), of 0.82 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,43 (t, J= 7 Hz, 2H), 3,55 (t, J= 8 Hz, 2H), 5,17 (s, 2H), 5,61 (d, J= 3.5 Hz, H), 5,68 (ush., 2H), 6,38 (DD, J= 3.5 and 1.5 Hz, 1H), 7,07 (d, J= 8.5 Hz, 2H), 7,19 (d, J= 8.5 Hz, 2H), was 7.36 (t ush., J= 7.5 Hz, 1H), 7,43 (t ush., J= 7.5 Hz, 2H), 7,50 (d ush., J= 7.5 Hz, 2H), to 7.59 (s, 1H), to 7.61 (d, J= 1.5 Hz, 1H), to 8.20 (s, 1H), of 10.58 (array, 1H).

Mass spectrum (EI): m/z = 581 M+;

m/z = 464 [M-OCH2CH2Si(CH3)3]+;

m/z = 91 [C6H5CH2]+.

N-[5-(2-Furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]-butanamide

To 1.20 g of N-[5-(2-furanyl)6-[4-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 50 cm3tetrahydrofuran (THF) add 12,4 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 75 cm3ethyl acetate and the organic phase is washed successively with 2 times 50 cm3saturated sodium hydrogen carbonate solution and with 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 1.5 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and you arevut under reduced pressure (2 kPa; 50aboutC); the residue is dried (90 PA; 45aboutC)receiving 750 mg of N-[5-(2-furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,42 (t, J= 7 Hz, 2H), 5,16 (s, 2H), ceiling of 5.60 (d, J= 3.5 Hz, 1H), 6,37 (DD, J= 3.5 and 1.5 Hz, 1H), 7,06 (d, J= 8.5 Hz, 2H), 7,20 (d, J= 8.5 Hz, 2H), 7,28 (s, 1H)that was 7.36 (t ush., J= 7.5 Hz, 1H), 7,43 (t ush., J= 7.5 Hz, 2H), 7,51 (l ush., J= 7.5 Hz, 2H), to 7.59 (ush., 1H), 8,15 (s, 1H), 10,44 (array, 1H)of 12.73 (array, 1H).

Mass spectrum (EI): m/z = 451 M+;

m/z = 381 [M-C4H6O]+.

N-[5-(2-Furanyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide

To 750 mg of N-[5-(2-furanyl)-6-[4-(phenylmethoxy)phenyl]-1H-indazol-3-yl]butanamide described above, add 10 cm3trimethylsilylmethyl and refluxed for 18 hours. In medium was added 40 cm3methanol and continue boiling under reflux for 10 minutes, then the reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The residue is treated with 75 cm3ethyl acetate and 50 cm3of tetrahydrofuran and the organic phase is washed 2 times with 75 cm310%-aqueous solution of sodium thiosulfate, then with 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, then concentrated dosa is as under reduced pressure, receiving 700 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 2.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio 50:50 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 3 cm3ethyl acetate, filtered off, washed with 2 cm3ethyl acetate, then 15 cm3diisopropyl ether and dried (90 PA; 45aboutC)receiving 10 mg of N-[5-(2-furanyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide in the form of white crystals, melting at 190aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,43 (t, J= 7 Hz, 2H), to 5.58 (d, J= 3.5 Hz, 1H), 6,38 (DD, J= 3.5 and 1.5 Hz, 1H), 6,80 (d, J= 8.5 Hz, 2H), was 7.08 (d, J= 8.5 Hz, 2H), 7,26 (s, 1H), to 7.59 (ush, 1H), to 8.14 (s, 1H), 9,54 (array, 1H), 10,44 (array, 1H), 12,70 (array, 1H).

Example 103

N-[5-Bromo-6-chloro-7-nitro-1H-indazol-3-yl]butanamide

To 4 g of N-[5-bromo-6-chloro-1H-indazol-3-yl]butanamide described in example 58, 50 cm3acetonitrile, at a temperature of 0aboutTo add 418 mg detroitmetroairport and stirred for 4 hours. In the reaction medium was added 200 cm3ethyl acetate and 100 cm3a saturated solution of sodium bicarbonate. Organicheskoi the phase is washed 2 times by 40 cm 3a saturated solution of sodium bicarbonate, then with 40 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 840 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC), then dried (90 PA; 45aboutC)receiving 20 mg of N-[5-bromo-6-chloro-7-nitro-1H-indazol-3-yl]butanamide in a solid yellow color, melting at a temperature above 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,44 (t, J= 7 Hz, 2H), to 8.70 (s, 1H), 10,80 (array, 1H), 13,63 (array, 1H).

Mass spectrum (EI): m/z = 360 M+;

m/z = 290 [M-C4H6O]+.

Example 104

N-(6,7-Debtor-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1.65 g of sodium hydride (60%in oil) in 50 cm3of dimethylformamide is added dropwise a solution of 1.1 g of N-(6,7-debtor-1H-indazol-3-yl)butanamide obtained according to example 40, 180 cm3of dimethylformamide for 3 hours. The reaction with the food concentrate to dryness under reduced pressure and treated with 250 cm 3ethyl acetate and 200 cm3water; the organic phase is decanted, washed with 150 cm3water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 6 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving of 7.3 g of N-[6,7-debtor-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]-butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), of 0.82 (t, J= 8 Hz, 2H), of 0.96 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2,41 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), to 5.66 (s, 2H), 7,22 (DDD, J= 11 and 9 and 7 Hz, 1H), 7,69 (DD ush., J= 9 and 4.5 Hz, 1H), or 10.60 (array, 1H).

Mass spectrum (EI): m/z = 369 M+;

m/z = 252 [M-OCH2CH2Si(CH3)3]+;

m/z = 241 [M-C6H12OSi]+.

N-(5-Bromo-6,7-debtor-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-(6,7-debtor-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3chloroform add to 0.87 cm3pyridine, then add to 0.56 cm3bromine and refluxed over night. In the reaction environment is in add 50 cm 3dichloromethane and 50 cm310%aqueous sodium thiosulfate solution. After stirring for 10 minutes, the insoluble portion removed by filtration on a glass Frit and the organic phase is washed with 50 cm3water and 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The crude product in the amount of 1.1 g purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 90:10 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 45about(C) obtain 230 mg of N-[5-bromo-6,7-debtor-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a colorless oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N), from 0.84 (t, J= 8 Hz, 2H), of 0.95 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,43 (t, J= 7 Hz, 2H)and 3.59 (t, J= 8 Hz, 2H), 5,69 (s, 2H), 7,40-the 7.65 (m, 5H), 7,82 (l ush., J= 7 Hz, 1H), at 10.64 (array, 1H).

Mass spectrum (EI): m/z = 447 M+;

m/z = 330 [M-OCH2CH2Si(CH3)3]+;

m/z = 319 [M-C6H12OSi]+.

N-(5-Bromo-6,7-debtor-1H-indazol-3-yl)butanamide

To 700 mg of N-(5-the rum-6,7-debtor-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide, as described above, in 30 cm3tetrahydrofuran (THF) add 9.4 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; after cooling, add 100 cm3ethyl acetate and 75 cm3saturated sodium hydrogen carbonate solution, then the organic phase is washed successively with 75 cm3a saturated solution of sodium bicarbonate and 75 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 850 mg of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 8 cm3diisopropyl ether, filtered off, washed with 3 cm3diisopropyl ether, dried under reduced pressure (90 PA; 45aboutC)receiving 200 mg of N-(5-bromo-6,7-debtor-1H-indazol-3-yl)butanamide in the form of white crystals, melting at 220aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in d: of 0.95 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,41 (t, J= 7 Hz, 2H), 8,03 (DD, J= 6 and 2 Hz, 1H), of 10.58 (ush., 1H), 13.56MHz (array, 1H).

Example 105

N-[6-(4-Cyanophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 500 mg of N-[6-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, obtained as described in example 51, 100 cm3dioxane add 853 mg 4-cyanophenylacetic acid, 15 cm3water, 1.0 g of sodium carbonate and 314 mg tetranitroaniline. The reaction medium is then refluxed for 4 hours and diluted with 70 cm3ethyl acetate and 75 cm3water. The organic phase is decanted, washed with 50 cm3distilled water, then 2 times 50 cm3saturated aqueous solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 45aboutC). The obtained residue in the amount of 2.0 g purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutS); obtain 1.0 g of N-[6-(4-cyanophenyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a solid which CSOs substances yellow melting at 136aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,43 (t, J= 7 Hz, 2H), to 3.58 (t, J= 8 Hz, 2H), USD 5.76 (s, 2H), 7,53 (l ush., J= 8.5 Hz, 1H), 7.95 is-with 8.05 (m, 4H), of 7.97 (d, J= 8.5 Hz, 1H), 8,11 (s, 1H), 10,55 (array, 1H).

N-[6-(4-Cyanophenyl)-1H-indazol-3-yl]butanamide

To 400 mg of N-[6-(4-cyanophenyl)-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide described above, in 10 cm3tetrahydrofuran (THF) add 3.0 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours. The reaction medium is diluted with 20 cm3ethyl acetate and the organic phase is washed successively with 20 cm3saturated sodium hydrogen carbonate solution, 2 times with 20 cm3of water and with 20 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira gradient mixture of dichloromethane and methanol (in a ratio of from 100:0 to 98:2 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 0 aboutC); receive 120 mg of N-[6-(4-cyanophenyl)-1H-indazol-3-yl]butanamide in the form of a solid, melting at 242aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 7,42 (l ush., J= 9 Hz, 1H), 7,74 (ush., 1H), 7,92 (d, J= 9 Hz, 1H), of 7.96 (s, 4H), 10,37 (array, 1H), 12,81 (array, 1H).

Example 106

N-[6,7-Debtor-5-nitro-1H-indazol-3-yl]butanamide

To a suspension of 500 mg of N-[6,7-debtor-1H-indazol-3-yl]-butanamide obtained according to example 40, 30 cm3acetonitrile, cooled to a temperature of 0aboutTo add 555 mg detroitmetroairport. After reaction for 30 minutes in the reaction medium was added 50 cm3ethyl acetate and 50 cm3a saturated solution of sodium bicarbonate. The organic phase is decanted, washed with 50 cm3water and 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 630 mg of a brown oil. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled, evaporated under reduced pressure (2 kPa; 50the C) and dried (90 PA; 45aboutC)receiving 300 mg of N-[6,7-debtor-5-nitro-1H-indazol-3-yl]butanamide in the form of yellow crystals, melting at 255aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm as 0.96 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,45 (t, J= 7 Hz, 2H), 8,89 (DD, J= 6.5 and 2 Hz, 1H), 10,94 (array, 1H), 14,05 (array ush., 1H).

Mass spectrum (EI): m/z = 284 M+;

m/z = 214 [M-C4H6O]+.

Example 107

N-[6,7-Debtor-5-phenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1,15 g of N-(5-bromo-6,7-debtor-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl)butanamide obtained according to example 104, 150 cm3dioxane add 469 mg of phenylboronic acid, 760 mg of sodium carbonate in 30 cm3water and 379 mg tetranitroaniline and refluxed for 4 hours. The reaction medium is diluted with 100 cm3ethyl acetate and 75 cm3water and filtered through a porous glass filter with telicom. The organic phase is decanted, washed with 75 cm3water and 75 cm3a saturated solution of sodium chloride, dried over sulfinol magnesium, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving 2 g of crude product as oil black. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column with what silicagel (the grading of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio of 85:15 by volume). The fractions containing the desired product are pooled, evaporated under reduced pressure (2 kPa; 50aboutC) and dried (90 PA; 45aboutC)obtaining 1.1 g of N-[6,7-debtor-5-phenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,05 (s, N), from 0.84 (t, J= 8 Hz, 2H), of 0.95 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,43 (t, J= 7 Hz, 2H)and 3.59 (t, J= 8 Hz, 2H), 5,69 (s, 2H), 7,40-the 7.65 (m, 5H), 7,82 (l ush., J= 7 Hz, 1H), at 10.64 (array, 1H).

Mass spectrum (EI): m/z = 445 M+;

m/z = 328 [M-OCH2CH2Si(CH3)3]+;

m/z = 317 [M-C6H12OSi]+.

N-(6,7-Debtor-5-phenyl-1H-indazol-3-yl)butanamide

To 1.1 g of N-[6,7-debtor-5-phenyl-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 50 cm3tetrahydrofuran (THF) add 14,8 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; in case of incomplete reaction add 9.9 cm3solution tetrabutylammonium and continue boiling under reflux for 18 hours. After cooling, add 100 cm3ethyl acetate and 75 cm3a saturated solution of sodium bicarbonate; the organic phase is decanted and washed the Ute with 50 cm 3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa; 50aboutC)obtaining 1.3 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in a ratio of from 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the resulting solid is treated with 20 cm3diisopropyl ether, filtered off on a glass Frit, washed with 5 cm3ethyl acetate and 20 cm3diisopropyl ether, then dried (90 PA; 45aboutC)receiving 340 mg of N-(6,7-debtor-5-phenyl-1H-indazol-3-yl)butanamide in the form of a solid vatoobraznye substance of white color, melting at 224aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: of 0.95 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), 2,41 (t, J= 7 Hz, 2H), 7,40-of 7.60 (m, 5H), 7,76 (l ush., J= 6 Hz, 1H), 10,53 (array, 1H), 13,00-13,90 (array ush., 1H).

Mass spectrum (EI): m/z = 284 M+;

m/z = 245 [M-C4H6O]+.

Example 108

5-Bromo-2-[[2-(trimethylsilyl)ethoxy]methoxy]pyridine

To 717 mg of sodium hydride (60%in oil) in 50 cm3of dimethylformamide add a solution of 2.6 g of 5-bromo-2-Ki is oxypyridine 80 cm 3of dimethylformamide for 30 minutes and stirred for 1 hour at room temperature. The dimethylformamide is removed under reduced pressure and the residue is treated with 75 cm3ethyl acetate and 50 cm3water; the organic phase is decanted, washed twice with 50 cm3water and 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)receiving a yellow oil. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in a ratio of from 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 2.64 g of 5-bromo-2-[[2-(trimethylsilyl)ethoxy]methoxy]pyridine in the form of a yellow oil, which is used by tel Quel in the following experience.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,02 (s, N), to 0.89 (t, J= 8 Hz, 2H), of 3.73 (t, J= 8 Hz, 2H), 5,49 (s, 2H), 6.89 in (l ush., J= 8.5 Hz, 1H), of 7.96 (DD, J= 8.5 and 2.5 Hz, 1H), 8,31 (l ush., J= 2.5 Hz, 1H).

Mass spectrum (DCI): m/z = 304 [M+H]+.

N-[6-[6-[[2-(Trimethylsilyl)ethoxy]methoxy]pyridyl-3-yl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(three is lilcely)ethoxy]methyl]-1H-indazol-3-yl]butanamide, obtained according to example 56, 70 cm3dioxane is added 1.19 g of 5-bromo-2-[[2-(trimethylsilyl)ethoxy]methoxy]pyridine obtained above, and to the solution blignault colors add 201 mg tetranitroaniline and 646 mg of sodium carbonate in 10 cm3water and refluxed for 3 hours. The reaction medium is diluted with 75 cm3ethyl acetate and 50 cm3water and the reaction medium is filtered through a porous glass filter with telicom. The organic phase is decanted, washed with 50 cm3water, 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 0.45 g of N-[6-[6-[[2-(trimethylsilyl)ethoxy]methoxy]pyridyl-3-yl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of orange varnish.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), 0,00 (s, N), or 0.83 (t, J= 8 Hz, 2H), of 0.93 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,41 (t, J= 7 Hz, 2H), of 3.56 (t, J=8 Hz, 2H), with 3.79 (t, J= 8 Hz, 2H), 5,59 (s, 2H), 5,74 (ush., 2H), 7,02 (d, J= 8.5 Hz, 1H), 7,47 (l ush., J= 8.5 Hz, 1H), 7,92 (d, J= 8.5 Hz, 1H), 8,00 (ush., 1H), 8,18 (DD, J= 8.5 and 2.5 Hz, 1H), 8,61 (d, J= 2.5 Hz, 1H), 10,53 (array, 1H).

Mass spectrum (EI): m/z = 556 M+;

m/z = 439 [M-OCH2CH2Si(CH3)3]+;

m/z = 73 [Si(CH3)3]+.

N-[6-(6-Hydroxypyridine-3-yl)-1H-indazol-3-yl]butanamide

To 0.73 g of N-[6-[6-[[2-(trimethylsilyl)ethoxy]methoxy]-pyridyl-3-yl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 15 cm3tetrahydrofuran (THF) add 15,7 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 18 hours; in case of incomplete reaction continue boiling under reflux for 18 hours. After cooling, add 60 cm3ethyl acetate and the organic phase is washed with 30 cm3a saturated solution of sodium bicarbonate, then 2 times in 30 cm3water and 30 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC)obtaining 1.3 g of crude product which is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira gradient mixture of dichloro ETANA and methanol (in a ratio of from 95:5 to 90:10 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 270 mg still contaminated product, which is again purified by high-performance liquid chromatography (column X-Terra; C18, 5 μm; length 100 mm, diameter 30 mm; eluting agent: a mixture of methanol and water (sootnoshenii 70:30 by volume)containing 0.05 % triperoxonane acid; flow rate: 20 cm3/min). After concentration of fractions containing the target product, and drying (90 PA; 45about(C) receive 40 mg of N-[6-(6-hydroxypyridine-3-yl)-1H-indazol-3-yl]butanamide in the form of a solid, melting at a temperature above 260aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 6,47 (d, J= 9.5 Hz, 1H), 7,25 (l ush., J= 9 Hz, 1H), 7,52 (ush., 1H), to 7.77 (d, J= 2.5 Hz, 1H), 7,81 (d, J= 9 Hz, 1H), of 7.90 (DD, J= 9.5 and 2.5 Hz, 1H), 10.30 a.m. (ush., 1H), 11,83 (array, 1H), br12.62 (array, 1H).

Mass spectrum (EI): m/z = 296 M+;

m/z = 226 [M-C4H6O]+.

Example 109

N-[6-(2,2-Diphenylene[1,3]dioxol-5-yl)-1-[[2-(trimethylsilyl)-ethoxy]methoxy]-1H-indazol-3-yl]butanamide

To 1.2 g of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to example 56, 80 cm3dioxane add to 1.38 g 5-bromo-2,2-diphenyl-1,3-benzodioxole, obtained according to the European patent 303172-A2, and the solution is pale yellow add 242 mg tetranitroaniline and 688 mg of sodium carbonate in 10 cm3water and refluxed for 4 hours. The reaction medium is diluted with 50 cm3ethyl acetate and 50 cm3water, then filtered through a porous glass filter with telicom. The filtrate is decanted and the organic phase is washed with 50 cm3water and 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 840 mg of N-[6-(2,2-diphenyl-1,3-benzodioxol-5-yl)-1-[[2-(trimethylsilyl)ethoxy]methoxy]-1H-indazol-3-yl]butanamide in the form of a solid adhesive orange color.

Mass spectrum (EI): m/z = 605 M+;

m/z = 488 [M-OCH2CH2Si(CH3)3]+.

N-[6-(3,4-Dihydroxyphenyl)-1H-indazol-3-yl]butanesulfonate

To 0.8 g of N-[6-(2,2-diphenyl-1,3-benzodioxol-5-yl)-1-[[2-(trimethylsilyl)ethoxy]methoxy]-1H-indazol-3-yl]butanamide, poluchennogo the above, add 10 cm3trimethylsilylmethyl and refluxed for 3 hours, then carefully add 50 cm3methanol and continue boiling under reflux for 15 minutes. Reaction medium was concentrated to dryness under reduced pressure (2 kPa; 50aboutC) and the residue is treated with 50 cm3ethyl acetate and 100 cm310%sodium thiosulfate solution; the resulting insoluble portion removed by filtration and the filtrate is decanted. The organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira gradient mixture of dichloromethane and 7 n ammonia solution in methanol (in a ratio of 97:3 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 150 mg still contaminated product, which is again purified by high-performance liquid chromatography (column X-Terra; C18, 5 μm; length 100 mm, diameter 30 mm; eluting agent: gradient mixture of acetonitrile and water (in a ratio of from 15:85 to 45:55 by volume)containing 0.05% triperoxonane acid; flow rate: 20 cm3/min). After concentration of the fractions containing the whole is howling product, and drying (90 PA; 45about(C) receive 30 mg of N-[6-(3,4-dihydroxyphenyl)-1H-indazol-3-yl]butanesulfonate in the form of a powder brown color, melting at 236aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 6,85 (d, J= 8 Hz, 1H), 7,01 (DD, J= 8 and 2 Hz, 1H), 7,10 (d, J= 2 Hz, 1H), 7,26 (l ush., J= 9 Hz, 1H), 7,46 (ush, 1H), 7,79 (d, J= 9 Hz, 1H), 8,80-of 9.30 (array ush., 2H) 10,29 (ush., 1H), 12,57 (array, 1H).

Mass spectrum (EI): m/z = 311 M+;

m/z = 241 [M-C4H6O]+.

Example 110

N-[6-(1,3-Benzodioxol-5-yl)-1-[[2-(trimethylsilyl)ethoxy]-methoxy]-1H-indazol-3-yl]butanamide

To 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide described above, in 30 cm3dioxane add 677 g of 1,3-benzodioxol-5-yl-Bronevoy acid, 1.24 g of cesium fluoride, then 13.5 mg of palladium acetate and finally 31 mg of 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl. Then heated at a temperature of 94aboutC for 15 hours, and then held until it reaches again the temperature of the 19aboutC, then the reaction medium is filtered through a porous glass filter with telicom. Washed with ethyl acetate, then the organic phase is dried over magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure (2 kPa; 45aboutC). The residue is purified by chromatography under a pressure of argon of 50 KP is on a column of silica gel (grain size distribution 15-40 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume); the fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). Obtain 620 mg of N-[6-(1,3-benzodioxol-5-yl)-1-[[2-(trimethylsilyl)ethoxy]methoxy]-1H-indazol-3-yl]butanamide as a sticky oil is light yellow in color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), and 0.98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2,41 (t, J= 7 Hz, 2H), of 3.56 (t, J= 8 Hz, 2H), 5,74 (ush., 2H), 6,10 (s, 2H), 7,05 (d, J= 8 Hz, 1H), 7,27 (DD, J= 8 and 2 Hz, 1H), 7,37 (d, J= 2 Hz, 1H), 7,42 (DD ush., J= 9 and 1.5 Hz, 1H), 7,86 (d, J= 9 Hz, 1H), 7,89 (ush., 1H), 10,45 (array, 1H).

Mass spectrum (EI): m/z = 493 M+;

m/z = 336 [M-OCH2CH2Si(CH3)3]+;

m/z = 325 [M-C6H12OSi]+.

N-[6-(1,3-Benzodioxol-5-yl)-1H-indazol-3-yl]butanamide

To 600 mg of N-[6-(benzodioxol-5-yl)-1-[[2-(trimethylsilyl)-ethoxy]methoxy]-1H-indazol-3-yl]butanamide described above, in 12 cm3of tetrahydrofuran is added 2 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran. The medium is then heated at a temperature of 67aboutC for 16 hours. Then held until it reaches again the temperature of the 19aboutWith and add 60 cm3ethyl acetate, then washed with 30 cm3saturated aqueous sodium hydrogen carbonate solution, and then 2 times in 30 cm 3distilled water and finally with 30 cm3saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulfate, filtered through a porous glass filter and evaporated under reduced pressure (2 kPa; 45aboutC). The resulting residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution 15-40 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume) and collecting fractions 15 cm3. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC). After drying (90 PA; 50about(C) obtain 260 mg of N-[6-(1,3-benzodioxol-5-yl)-1H-indazol-3-yl]butanamide in a solid white color, melting at 240aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), by 1.68 (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 6,09 (s, 2H), 7,03 (d, J= 8 Hz, 1H), 7,21 (DD, J= 8 and 2 Hz, 1H), 7,30 (DD ush., J= 9 and 1.5 Hz, 1H), 7,31 (d, J= 2 Hz, 1H), 7,55 (ush., 1H), 7,82 (d, J= 9 Hz, 1H), 10,31 (ush., 1H), 12,63 (ush., 1H).

Mass spectrum (EI): m/z = 323 M+;

m/z = 253 [M-C4H6O]+.

Example 111

N-[7-Fluoro-5-nitro-6-[2-(phenylethyl)amino]-1H-indazol-3-yl]-butanamide

To a solution of 500 mg of N-(6,7-debtor-5-nitro-1H-indazol-3-yl)-butanamide obtained according to example 106, 10 cm3dimethyl sulfoxide add recipients who have 1,11 cm 3phenethylamine and refluxed for 1 hour. The reaction medium is treated with 50 cm3ethyl acetate and the organic phase is washed 4 times by 35 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure, obtaining 1.5 g of oil. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution 15-40 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 70:30 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 30 cm3diethyl ether, filtered off on a glass Frit, washed with 2 times 20 cm3diethyl ether, then dried (90 PA; 50aboutC)receiving 360 mg of N-[7-fluoro-5-nitro-6-[(phenylethyl)amino]-1H-indazol-3-yl]butanamide in the form of a chestnut colored crystals, melting at 212aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm as 0.96 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2,42 (t, J= 7 Hz, 2H), 2,93 (t, J= 7 Hz, 2H), 3,76 (m, 2H), 7,03 (m, 1H), 7,15-7,40 (m, 5H), cent to 8.85 (s, 1H), of 10.73 (ush., 1H), 13,10 (array, 1H).

Mass spectrum (EI): m/z = 385 M+;

m/z = 294 [M-CH2C6H5]+;

m/z = 224 [294-C4H6O]sup> +.

Example 112

N-(7-Fluoro-5-nitro-6-morpholino-1H-indazol-3-yl)butanamide

Follow the procedure of example 110, on the basis of 500 mg of N-(6,7-debtor-5-nitro-1H-indazol-3-yl)butanamide obtained according to example 106, 10 cm3dimethyl sulfoxide, 0,77 cm3the research and refluxed for 1 hour. The reaction medium is treated with 75 cm3ethyl acetate and the organic phase is washed 2 times with 75 cm3water and 50 cm3a saturated solution of sodium chloride. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure, obtaining 1 g of oil chestnut color. The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution 15-40 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 30 cm3diethyl ether, filtered off on a glass Frit, washed with 2 times 20 cm3diethyl ether, then dried (90 PA; 50aboutC)receiving 280 mg of N-(7-fluoro-5-nitro-6-morpholino-1H-indazol-3-yl)butanamide in the form of a chestnut colored crystals, melting at 250aboutC.

1H-NMR-SP the crown-rump length (300 MHz, (CD3)2SO-d6), d in ppm as 0.96 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2,42 (t, J= 7 Hz, 2H), and 3.16 (m, 4H), of 3.69 (t, J= 4 Hz, 4H), 8,30 (ush., 1H), 10,75 (array, 1H), 13,68 (array, 1H).

Mass spectrum (EI): m/z = 351 M+;

m/z = 334 [M-OH]+.

Example 113

N-(7-Fluoro-5-amino-6-morpholino-1H-indazol-3-yl)butanamide

To a solution of 1.1 g of N-(7-fluoro-5-nitro-6-morpholino-1H-indazol-3-yl)butanamide obtained according to example 112, 50 cm3methanol add 200 mg 3%palladium-on-coal and 1 g of ammonium formate and stirred at room temperature for 18 hours. The reaction medium is filtered through a porous glass filter with telicom and concentrated to dryness under reduced pressure (2 kPa; 50aboutC), then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution 15-40 μm; diameter 3 cm), elwira a mixture of dichloromethane and methanol (ratio of 97.5:2.5 to by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the residue is treated with 20 cm3ethyl acetate, filtered off on a glass Frit, washed with 2 times 5 cm3ethyl acetate and with 10 cm3diethyl ether, then dried (90 PA; 50aboutC)receiving 306 mg of N-(7-fluoro-5-amino-6-morpholino-1H-indazol-3-yl)butanamide in the form of white crystals, melting at 180o C.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2,34 (t ush., J= 7 Hz, 2H), 3.04 from (array ush., 4H), of 3.77 (array ush., 4H), 4.95 points (with ush., 2H), 6,55 (s, 1H), there is a 10.03 (array, 1H), 13,57 (array, 1H).

Mass spectrum (EI): m/z = 321 M+;

m/z = 306 [M-CH3]+.

Example 114

N-(5-Bromo-7-fluoro-6-morpholino-1H-indazol-3-yl)butanamide

It cooled down to 5aboutFrom a suspension of 900 mg of N-(5-amino-7-fluoro-6-morpholino-1H-indazol-3-yl)butanamide obtained as described above, in 9 cm3water and 0.94 cm348%Hydrobromic acid is added dropwise a solution of 213 mg of sodium nitrite in 9 cm3water and stirred at a temperature of 0aboutC. This suspension in small portions add to the solution at boiling temperature under reflux, 482 mg of bromide monovalent copper, 4.5 cm3water and 4.5 cm348%Hydrobromic acid. Boiling under reflux continued for 45 minutes, then the reaction medium is filtered through a porous glass filter, and then dissolved in 75 cm3of tetrahydrofuran and purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution 15-40 μm; diameter 3 cm), elwira with a mixture of cyclohexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under lowered the th pressure (2 kPa; 50aboutC); the residue is treated with 10 cm3ethyl acetate, filtered and washed with 2 times 5 cm3ethyl acetate and 20 cm3diisopropyl ether. After filtration and drying (90 PA; 45about(C) receive 60 mg of N-(5-bromo-7-fluoro-6-morpholino-1H-indazol-3-yl)butanamide in the form of white crystals, melting at 240aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm as 0.96 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), of 2.38 (t, J= 7 Hz, 2H), and 3.16 (array, 4H), 3,76 (array, 4H), of 7.96 (s, 1H), 10,48 (array, 1H), 13,20 (array, 1H).

Mass spectrum (EI): m/z = 384 M+;

m/z = 314 [M-C4H6O]+.

Example 115

N-[7-Fluoro-6-(trifluoromethyl)-1H-indazol-3-yl]butanamide

To 2.1 g of 7-fluoro-6-(trifluoromethyl)-1H-indazol-3-amine, obtained as described in International application WO-0222608, 20 cm3pyridine, after cooling to a temperature of 3aboutWith add 1.0 cm3butyrylcholine, then incubated at achieving again at room temperature for 76 hours. Reaction medium was concentrated under reduced pressure (2 kPa; 40aboutC) and the residue is treated with 50 cm3ethyl acetate and 20 cm3water. The organic phase is washed with 2 times 20 cm3distilled water, then with 20 cm3saturated aqueous solution of sodium chloride. After drying over with what LifeCam magnesium, filtration and concentration under reduced pressure (2 kPa; 40about(C) the obtained residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira with a mixture of cyclohexane and ethyl acetate (in the ratio of 60:40 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 40aboutC); after drying (90 PA; 40about(C) receive 875 mg of N-[7-fluoro-6-(trifluoromethyl)-1H-indazol-3-yl]butanamide in a solid pink color, melting at 220-222aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,98 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2,42 (t, J= 7 Hz, 2H), 7,31 (DD, J= 8.5 and 6 Hz, 1H), 7,82 (l ush., J= 8.5 Hz, 1H), 10,59 (array, 1H), 13,50-14,20 (array ush., 1H).

Mass spectrum (EI): m/z = 289 M+;

m/z = 270 [M-F]+;

m/z = 219 [M-C4H6O]+.

Example 116

6-Bromo-4,5,7-Cryptor-1H-indazol-3-amine

To 2.0 g of 4-bromo-2,3,5,6-tetrafluorobenzoate 40 cm3absolute ethanol is added to 1.14 cm3hydrazinoacetate. Refluxed for 18 hours, then add 30 cm3distilled water and the reaction medium was concentrated under reduced pressure (2 kPa; 50aboutC). The residue is treated with 100 cm3ethyl acetate and 10 cm3water and the organic phase decanter the Ute, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC); after drying (90 PA; 40about(C) obtain 2.1 g of 6-bromo-4,5,7-Cryptor-1H-indazol-3-amine in the form of a solid beige color.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 5,52 (s, 2H), 12,10-12,90 (array ush., 1H).

Mass spectrum (EI): m/z = 265 M+;

m/z = 236 [M-HN2]+;

m/z = 186 [M-Br]+.

N-(6-Bromo-4,5,7-Cryptor-1H-indazol-3-yl)butanamide

To 2.1 g of 6-bromo-4,5,7-Cryptor-1H-indazol-3-amine obtained above, 20 cm3pyridine, after cooling to a temperature of 3aboutWith the add of 0.82 cm3butyrylcholine, then incubated at achieving again at room temperature for 76 hours. Reaction medium was concentrated under reduced pressure (2 kPa; 40aboutC) and the residue is treated with 100 cm3ethyl acetate, 100 cm3of tetrahydrofuran and 40 cm3water. The organic phase is washed with 2 times 40 cm3distilled water, then with 40 cm3saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, filtration and concentration under reduced pressure (2 kPa; 40about(C) the obtained residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4 cm), elwira mixture qi is lorexane and ethyl acetate (ratio 80:20 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 40aboutC); after drying (90 PA; 40about(C) gain of 0.53 g of N-(6-bromo-4,5,7-Cryptor-1H-indazol-3-yl)butanamide in a solid pink color, melting at 255-257aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,97 (t, J= 7.5 Hz, 3H), of 1.66 (m, 2H), a 2.36 (t, J= 7 Hz, 2H), 10,26 (array, 1H), 13,50-14,40 (array ush., 1H).

Mass spectrum (EI): m/z = 335 M+;

m/z = 265 [M-C4H6O]+.

Example 117

N-[6-(6-Aminopyridine-3-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide

To 1.0 g of N-[6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide obtained according to example 56, 50 cm3dioxane is added 0.45 g of 2-amino-5-bromopyridine and to the solution blignault color added 142 mg dichloro[1,1'-bis(diphenylphosphino)-ferrocene]palladium dichloromethane and 646 mg of sodium carbonate in 10 cm3water and refluxed for 2 hours. The reaction medium is diluted with 50 cm3ethyl acetate and 50 cm3water, then filtered through a porous glass filter with telicom. The filtrate is decanted and the organic phase is washed with 2 times 50 cm3a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and conc is tryout to dryness under reduced pressure (2 kPa; 50aboutC). The resulting crude product was then purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3 cm), elwira gradient of mixtures of cyclohexane and ethyl acetate (in a ratio of from 70:30 to 50:50 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC)receiving 0.53 mg N-[6-(6-aminopyridine-3-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a solid, melting at 138aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: - 0,09 (s, N), or 0.83 (t, J= 8 Hz, 2H), 0,97 (t, J= 7.5 Hz, 3H), 1,67 (m, 2H), 2,39 (t, J= 7 Hz, 2H), 3,55 (t, J= 8 Hz, 2H), 5,70 (s, 2H), 6,12 (s, 2H), to 6.57 (d, J= 9 Hz, 1H), 7,37 (DD, J= 8.5 and 1.5 Hz, 1H), 7,80-of 7.90 (m, 3H), of 8.37 (d, J= 2 Hz, 1H), 10,43 (array, 1H).

Mass spectrum (EI): m/z = 425 M+;

m/z = 308 [M-OCH2CH2Si(CH3)3]+;

m/z = 297 [M-C6H12OSi]+.

N-[6-(6-Aminopyridine-3-yl)-1H-indazol-3-yl]butenonitrile

To 0.8 g of N-[6-(6-aminopyridine-3-yl)-1-[[2-(trimethylsilyl)-ethoxy]methyl]-1H-indazol-3-yl]butanamide, obtained above, in 13 cm3tetrahydrofuran (THF) added 3.8 cm3tetrabutylammonium in the form of a 1 M solution in tetrahydrofuran and refluxed for 6 hours, then add 50 cm3etilatsetata and 25 cm3a saturated solution of hydro is of carbonate sodium. The organic phase is decanted, washed with 25 cm3water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude product is purified by high-performance liquid chromatography (column X-Terra; C18, 5 μm; length 50 mm, diameter 21 mm; eluting agent: gradient mixture of acetonitrile and water (in a ratio of from 5:95 to 95:5 by volume)containing 0.05% triperoxonane acid; flow rate: 20 cm3/min). After concentration of the fractions containing the desired product, get a solid substance, which is treated with 10 cm3diisopropyl ether and 2 cm3acetonitrile, filtered off, washed with 5 cm3diisopropyl ether and dried (90 PA; 45aboutC)receiving 18 mg of N-[6-(6-aminopyridine-3-yl)-1H-indazol-3-yl]butanilicaine in the form of white crystals, melting at 230-235aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: 0,99 (t, J= 7.5 Hz, 3H), 1.69 in (m, 2H), 2.40 a (t, J= 7 Hz, 2H), 7,05 (d, J= 9.5 Hz, 1H), 7,33 (DD, J= 8.5 and 1.5 Hz, 1H), 7,65 (ush., 1H), 7,79 (array, 2H), of 7.90 (d, J= 8.5 Hz, 1H), 8,31 (DD, J= 9.5 and 1.5 Hz, 1H), at 8.36 (d, J= 1.5 Hz, 1H), 10,37 (ush., 1H), 12,79 (array, 1H).

Mass spectrum (EI): m/z = 295 M+;

m/z = 225 [M-C4H6O]+;

m/z = 43 [C3H7]+.

Example 118

2-Chloro-N-(6,7-debtor-1H-indazol-3-yl)ndimethylacetamide

To 5 g of 6,7-d is fluorine-1H-indazol-3-amine, obtained according to example 40, 300 cm3toluene added 5.0 g of Chloroacetic anhydride acid and refluxed for 18 hours. The precipitation is concentrated to dryness under reduced pressure (2 kPa; 50aboutC), then the resulting residue is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 4.5 cm), elwira a mixture of dichloromethane and methanol (in a ratio of 98:2 by volume). The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC), then dried (90 PA; 45aboutC)obtaining 8.5 g of 2-chloro-N-(6,7-debtor-1H-indazol-3-yl)ndimethylacetamide in the form of a crystalline mass of cream color.

1H-NMR-spectrum (400 MHz, (CD3)2SO-d6at a temperature of 353 K), d in ppm: 4,37 (s, 2H), 7,11 (DDD, J= 8,5 - 7.5 and 5 Hz, 1H), to 7.67 (DD ush., J= 7.5 and 3 Hz, 1H), 10,65 (ush., 1H), 13,30 (array, 1H).

Mass spectrum (EI): m/z = 245 M+;

m/z = 169 [M-C2HOCl]+;

m/z = 140 [169-HN2]+.

N-(6,7-Debtor-1H-indazol-3-yl)-1-piperidineacetate

Follow the procedure of example 75, from 8.5 g of 2-chloro-N-(6,7-debtor-1H-indazol-3-yl)ndimethylacetamide, 200 cm3acetonitrile, 8,8 cm3of piperidine. The reaction medium is refluxed for 1 hour, then the precipitation is filtered off on a glass Frit, and crystals treated with 200 from the 3ethyl acetate and 100 cm3water. The organic phase is decanted, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50aboutC). The crude product is purified by chromatography under a pressure of argon of 50 kPa on a column of silica gel (grain size distribution of 40-60 μm; diameter 3.5 cm), elwira with ethyl acetate. The fractions containing the desired product are pooled and evaporated under reduced pressure (2 kPa; 50aboutC); the remainder will recrystallized from a mixture of 50 cm3cyclohexane and 16 cm3ethyl acetate, filtered and dried (90 PA; 45aboutC)obtaining 3.2 g of N-(6,7-debtor-1H-indazol-3-yl)-1-piperidineacetate in the form of white crystals, melting at 158aboutC.

1H-NMR spectrum (300 MHz, (CD3)2SO-d6), d in ppm: to 1.42 (m, 2H), 1,59 (m, 4H), 2,52 (m, 4H), 3,19 (s, 2H), 7,13 (DDD, J= 10,5 - 9 and 7 Hz, 1H), 7,66 (DD ush., J= 9 and 4.5 Hz, 1H), 10,14 (array, 1H), 13,42 (array, 1H).

Mass spectrum (DCI): m/z = 295 [M+H]+.

The pharmaceutical compositions according to the invention is formed by a compound of the formula (I) or the salt of such compounds in a pure state or in the form of a composition in which it is associated (associated) with any other pharmaceutically acceptable product, which can be inert or physiologically active. Medicinal product according to the invention can be administered orally, Parente the social, rectally or locally.

As solid compositions for oral administration can be used in tablets, pills, powders (gelatin capsules, starch wafers or pellets. In these compositions, the active principle according to the invention are mixed in a stream of argon, with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica. These compositions can also include, in addition to diluents, other substances, for example one or more lubricants such as magnesium stearate or talc, a colorant, a protective coating (coated tablets) or a varnish.

As liquid compositions for oral administration can be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or paraffin oil. These compositions can comprise substances other than diluents, for example wetting, sweetening, thickening agents, flavoring agents or stabilizers.

Sterile compositions for parenteral administration can be an aqueous or nonaqueous solutions, suspensions or emulsions. As a solvent or excipient you can use water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, complex organic is such esters for injection, for example etiloleat, or other suitable organic solvents. These compositions can also contain adjuvants, in particular wetting, isotonic components, emulsifiers, dispersing agents and stabilizers. Sterilization can be done in several ways, for example by asamisimasa filtration, by incorporating in the composition of sterilizing components, by irradiation or heating. They can also be obtained in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile environment for injection.

Compositions for rectal injection are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.

Compositions for local injection can be, for example, creams, lotions, lotions for the eyes, the liquid for rinsing the mouth and appliques on the gums, nasal drops or aerosols.

The object of the invention are derivatives of aminoindazole formula (I) and their pharmaceutically acceptable salts and their application to pharmaceutical compositions intended for the prevention and treatment of diseases that may occur due to abnormal activity of kinases, such as the er, actively involved in neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontoparietal dementia, kortiko-basal degeneration, diseases of the Peak, cerebrovascular disorders, cranial and spinal injuries and peripheral neuropathies, obesity, metabolic diseases, type II diabetes, essential hypertension, cardiovascular atherosclerotic diseases, polycystic ovary syndrome, syndrome X, immunodeficiency and cancer.

As abnormal activity of the kinase can be called, for example, PI3K, AkT, GSK3, CDK...

In human therapy, the compounds according to the invention is particularly suitable for the treatment and/or prevention of neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontoparietal dementia, kortiko-basal degeneration, diseases of the Peak, cerebrovascular disorders, cranial and spinal injuries and peripheral neuropathies, obesity, metabolic diseases, type II diabetes, essential hypertension, cardiovascular atherosclerotic diseases, polycystic ovary syndrome, syndrome X, immunodeficiency and cancer.

Doses depend on the desired effect, the duration of treatment and the route of administration; they typically range from 5 mg to 1000 mg per day when ingested by an adult when a singular is osah from 1 mg to 250 mg of active substance.

In General, the physician determines the appropriate dose depending on age, weight and all other factors relating to the patient.

The following examples illustrate compositions according to the invention.

Example

Prepared according to conventional methods, gelatin capsules with doses of 50 mg of active product having the following composition:

the compound of formula (I)50 mg
- cellulose18 mg
- lactose55 mg
gel of silicic acid1 mg
- sodium salt of carboxymethyl amylum10 mg
- talc10 mg
- stearate1 mg

The example In

Prepared according to conventional methods, pills with doses of 50 mg of active product having the following composition:

the compound of formula (I)

- lactose

- pulp

- polyvidone

- sodium salt of carboxymethyl amylum

- talc
50 mg

104 mg

40 mg

10 mg

22 mg

10 mg
- stearate

gel of silicic acid
2 mg

2 mg
a mixture of Hydra is climatically, glycerin,

titanium dioxide (72-3,5-24,5) to the total mass one, film-coated, end tablets, component 245 mg

Example

Prepare for a solution for injection containing 10 mg of active product, which has the following composition:

the compound of formula (I)

benzoic acid

- benzyl alcohol

- sodium benzoate

- ethanol, 95%

- sodium hydroxide

- propylene glycol

- water to total amount
10 mg

80 mg

0.06 ml

80 mg

0.4 ml

24 mg

1.6 ml

4 ml

The present invention relates also to a method for prevention and treatment of diseases, which is the phosphorylation of Tau-protein by introducing the compounds of formula (I) and its pharmaceutically acceptable salts.

1. The use of compounds of formula (I)

in which R means Of;

R3 means a radical (C1-With6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-quinil, and these radicals are not substituted or substituted by one or more substituents selected among halogen, C(O)OR8, phenyl, heteroaryl represents pyridyl, thienyl, triazolyl, azepin, formyl;

R4, R5, R6 and R7 independently on the angle from each other chosen from the following radicals: hydrogen atom, halogen, CN, NO2, NH2, NHSO2R9, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, phenyl, phenyl-(C1-C6)-alkyl, pyridyl, possibly substituted amino or hydroxy-group, thienyl, furanyl, morpholino, and phenyl is not substituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2HE, (C1-C6)-alkoxyl, NR10R11, trifloromethyl, cryptometer;

R8, R9, R10, R11 independently of one another mean a hydrogen atom, (C1-C6)-alkyl, phenyl, possibly substituted with halogen;

their racemates, enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts to obtain a drug that inhibits the phosphorylation of Tau-protein.

2. The use according to claim 1 compounds of formula (I)

in which R means Of;

R4 and R7 denote H;

R3 means a radical (C1-C6)-alkyl, (C2-C6)-alkenyl, and these radicals are not substituted or substituted by one or more substituents selected among halogen, COOH, C(O)OR8, phenyl, heteroaryl represents pyridyl, thienyl, triazolyl, azepin, formyl;

R5 and R6 independently from each other chosen from the following radicals: hydrogen, halogen, CN, NO 2, NH2, NHSO2R9, phenyl, phenyl-(C1-C6)-alkyl, pyridyl, possibly substituted amino or hydroxy-group, thienyl, furanyl, morpholino, and phenyl is not substituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2HE, alkoxy, NR10R11, trifloromethyl, cryptometer;

R8, R9, R10, R11 independently of one another mean a hydrogen atom, (C1-C6)-alkyl, phenyl, possibly substituted with halogen;

their racemates, enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts to obtain a drug that inhibits the phosphorylation of Tau-protein.

3. The compounds of formula (I)

in which R means Of;

R3 means a radical (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-quinil, and these radicals are not substituted or substituted by one or more substituents selected among halogen, C(O)OR8, phenyl, heteroaryl represents pyridyl, thienyl, triazolyl, azepin, formyl;

R4, R5, R6 and R7 independently from each other chosen from the following radicals: hydrogen, halogen, CN, NO2, NH2, NHSO2R9, trifluoromethyl, tripterocarpa, (C1-C6)-alkyl, phenyl, phenyl-(C1 6)-alkyl, pyridyl, possibly substituted amino or hydroxy-group, thienyl, furanyl, morpholino, and phenyl is not substituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2HE, (C1-C6)-alkoxyl, NR10R11, trifloromethyl, cryptometer;

R8, R9, R10, R11 independently of one another mean a hydrogen atom, (C1-C6)-alkyl, phenyl, possibly substituted with halogen;

their racemates, the enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts, except

N-(1H-indazol-3-yl)benzhydrylamine, N-(6-chloro-1H-indazol-3-yl)-2,2,2-trifurcated, N-(1H-indazol-3-yl)butanamide, N-(1H-indazol-3-yl)phenylacetamide, N-(5-nitro-1H-indazol-3-yl)ndimethylacetamide and 5-amino-3-acetamidophenol.

4. Compounds according to claim 3, characterized in that they correspond to the formula (I)

in which R means Of;

R4 and R7 denote H;

R3 means a radical (C1-C6)-alkyl, (C2-C6)-alkenyl, and these radicals are not substituted or substituted by one or more substituents selected among halogen, COOH, C(O)OR8, phenyl, heteroaryl represents pyridyl, thienyl, triazolyl, azepin, formyl;

R5 and R6 independently from each other chosen among the following the radicals: hydrogen atom, halogen, CN, NO2, NH2, NHSO2R9, phenyl, phenyl-(C1-C6)-alkyl, pyridyl, possibly substituted amino or hydroxy-group, thienyl, furanyl, morpholino, and phenyl is not substituted or substituted by one or more substituents selected among halogen, CN, NO2, NH2HE, (C1-C6)-alkoxyl, NR10R11, trifloromethyl, cryptometer;

R8, R9, R10, R11 independently of one another mean a hydrogen atom, (C1-C6)-alkyl, phenyl, possibly substituted with halogen;

their racemates, the enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts, except

N-(1H-indazol-3-yl)benzhydrylamine, N-(6-chloro-1H-indazol-3-yl)-2,2,2-trifurcated, N-(1H-indazol-3-yl)butanamide, N-(1H-indazol-3-yl)phenylacetamide, N-(5-nitro-1H-indazol-3-yl)ndimethylacetamide and 5-amino-3-acetamidophenol.)

5. The connection, characterized in that it is chosen from the

(2Z)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acids;

ethyl-(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate;

4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butane acid;

(2Z)-4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butenova acids;

(2E)-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenova acids;

4-[(5-bromo-1H-indazol-3-yl)amino]-4-oxo-2-butane acid;

(2E)-N-(6-chloro-1H-indazol-3-yl)-2-butanamide;

N-(6-chloro-1H-indazol-3-yl)-3-butenonitrile;

methyl-4-[(6-chloro-1H-indazol-3-yl)amino]-4-oxo-2-butenoate;

N-(6-chloro-1H-indazol-3-yl)ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)butanamide;

(2E)-N-(6-bromo-1H-indazol-3-yl)-2-butanamide;

(2E)-N-(5-methyl-1H-indazol-3-yl)-2-butanamide;

N-(6-chloro-1H-indazol-3-yl)-2-propenamide;

(2E)-N-(6-(trifluoromethyl)-1H-indazol-3-yl)-2-butanamide;

ethyl-4-[[6-(trifluoromethyl)-1H-indazol-3-yl]amino]-4-oxobutanoate;

(2E)-N-(5-(trifluoromethyl)-1H-indazol-3-yl)-2-butanamide;

N-[5-chloro-1H-indazol-3-yl]-2-butanamide;

N-[4-chloro-1H-indazol-3-yl]-2-butanamide;

N-[6-(trifluoromethyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]propanamide;

N-[5-(trifluoromethyl)-1H-indazol-3-yl]butanamide;

N-[5-nitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-1H-indazol-3-yl]butanamide;

N-[6-(3-pyridyl)-1H-indazol-3-yl]butanamide;

N-[4-iodine-1H-indazol-3-yl]butanamide;

N-[6-phenyl-1H-indazol-3-yl]butanamide;

N-[6-bromo-5,7-dinitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-7-nitro-1H-indazol-3-yl]butanamide;

N-[6-bromo-5-nitro-1H-indazol-3-yl]butanamide;

N-[(6-furan-3-yl)-1H-indazol-3-yl]butanamide;

N-[[6-(4-benzyloxy)phenyl]-1H-indazol-3-yl] b is tnamed;

N-[6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]benzolamide;

N-[6-(3,5-differenl)-1H-indazol-3-yl]butanamide;

N-[6-(3-thienyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2-thiopheneacetic;

N-[5-(3-forbindelseshandtering)-1H-indazol-3-yl]benzamide;

N-[6-(2-phenylethyl)-1H-indazol-3-yl]butanamide;

N-(6,7-debtor-1H-indazol-3-yl)butanamide;

N-[6-(4-methoxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-methylthiophenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-trifloromethyl)-1H-indazol-3-yl]butanamide;

N-[6-(2-propenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2-pyridinecarboxamide;

N-[6-(4-forfinal)-1H-indazol-3-yl]butanamide;

N-[6-[4-(1,1-dimethylethyl)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-bromo-7-amino-1H-indazol-3-yl]butanamide;

N-[6-[4-(trifluoromethyl)phenyl]-1H-indazol-3-yl]butanamide;

N-[6-(4-were)-1H-indazol-3-yl]butanamide;

N-[6-(3,5-dichlorophenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl] - for 3,5-dichlorobenzamide;

N-[6-(4-chlorophenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]benzoyltrifluoroacetone;

N - [6-chloro-1H-indazol-3-yl]benzoylpropionic;

N-[6-(4-ethylphenyl)-1H-indazol-3-yl]butane is a;

N-[6-(4-pyridinyl)-1H-indazol-3-yl]butanamide;

N-[5-amino-1H-indazol-3-yl]butanamide;

N-[5-bromo-6-chloro-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2-methylpropanamide;

4-chloro-M-[6-chloro-1H-indazol-3-yl]butanamide;

N-[5-phenyl-6-chloro-1H-indazol-3-yl]butanamide;

N-[5-bromo-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-(4-nitrophenyl)-1H-indazol-3-yl]butanamide;

N-[6-(2-chlorophenyl)-1H-indazol-3-yl]butanamide;

N-[6-(3-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-pyridinyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(3-furanyl)-1H-indazol-3-yl]butanamide;

N-[6-(2-chloro-4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5,6-dibromo-1H-indazol-3-yl]butanamide;

N-[6-chloro-1H-indazol-3-yl]-2,2,3,3,4,4,4-getattributename;

N-[6-chloro-5-(4-forfinal)-1H-indazol-3-yl]butanamide;

N-[6-(4-AMINOPHENYL)-1H-indazol-3-yl]butanamide;

N-[6-[4-(dimethylamino)phenyl]-1H-indazol-3-yl]butanamide;

N-(6-chloro-1H-indazol-3-yl)-4-methyl-1-piperazinecarboxamide;

N-(6-chloro-1H-indazol-3-yl)-1-piperidineacetate;

N-(6-chloro-1H-indazol-3-yl)-4-morpholinoethyl;

N-(6-chloro-1H-indazol-3-yl)-1H-1,2,4-triazole-1-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-2-(cyclohexylamino)ndimethylacetamide;

2-[(phenylmethyl)amino]-N-(6-PI is the p-1H-indazol-3-yl]ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-1H-azepin-1-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-1-piperazinecarboxamide;

N-(6-chloro-1H-indazol-3-yl)-2-[[3-(dimethylamino)propyl]amino]-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)thiomorpholine-4-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-1-pyrrolidineethanol;

N-(6-chloro-1H-indazol-3-yl)-2-[[2-(dimethylamino)ethyl]amino]-ndimethylacetamide;

N-(6-chloro-1H-indazol-3-yl)-1-cyclopropanecarboxylate;

N-(6-chloro-1H-indazol-3-yl)-1-cyclopropylbenzene;

N-(6-chloro-1H-indazol-3-yl)-2-(2-diethylaminoethylamine)-acetamidocinnamate;

N-(6-chloro-1H-indazol-3-yl)-2-(2-diethylaminoethylamine)ndimethylacetamide;

N-[5,6-diphenyl-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-were)-1H-indazol-3-yl]butanamide;

N-[5-phenyl-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-pyridinyl)-1H-indazol-3-yl]butanamide;

N-[5-(4-AMINOPHENYL)-6-chloro-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-ethylphenyl)-1H-indazol-3-yl]butanamide;

N-[6-chloro-5-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5,6-bis(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5-(3-furanyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5-(4-ethylphenyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[5-(3-pyridinyl)-6-(4-hydroxyben the l)-1H-indazol-3-yl]butanamide;

N-[5-(2-furanyl)-6-(4-hydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-(5-bromo-6-chloro-7-nitro-1H-indazol-3-yl)butanamide;

N-(5-bromo-6,7-debtor-1H-indazol-3-yl)butanamide;

N-[6-(4-cyanophenyl)-1H-indazol-3-yl]butanamide;

N-(6,7-debtor-5-nitro-1H-indazol-3-yl)butanamide;

N-(6,7-debtor-5-phenyl-1H-indazol-3-yl)butanamide;

N-[6-(6-hydroxypyridine-3-yl)-1H-indazol-3-yl]butanamide;

N-[6-(3,4-dihydroxyphenyl)-1H-indazol-3-yl]butanesulfonate;

N-[6-(3,4-dihydroxyphenyl)-1H-indazol-3-yl]butanamide;

N-[7-fluoro-5-nitro-6-[2-(phenylethyl)amino]-1H-indazol-3-yl]butanamide;

N-(7-fluoro-5-nitro-6-morpholino-1H-indazol-3-yl)butanamide;

N-(7-fluoro-5-amino-6-morpholino-1H-indazol-3-yl)butanamide;

N-(5-bromo-7-fluoro-6-morpholino-1H-indazol-3-yl)butanamide;

N-[7-fluoro-6-(trifluoromethyl)-1H-indazol-3-yl]butanamide;

N-(6-bromo-4,5,7-Cryptor-1H-indazol-3-yl)butanamide;

N-[6-(6-aminopyridine-3-yl)-1H-indazol-3-yl]-butenonitrile;

N-[6-(6-aminopyridine-3-yl)-1H-indazol-3-yl]butanamide;

2-chloro-N-(6,7-debtor-1H-indazol-3-yl)ndimethylacetamide;

N-(6,7-debtor-1H-indazol-3-yl)-1-piperidineacetate;

its racemate, its enantiomers, tautomers and their pharmaceutically acceptable salts.

6. The pharmaceutical composition inhibiting phosphor is licensing Tau-protein, characterized in that it contains in a pharmaceutically acceptable medium compound according to any one of p-5.

7. Drug, inhibitory phosphorylation of Tau - protein, characterized in that it contains at least one compound defined in any of p-5.

8. The method of obtaining compounds of formula (I), such as defined by claim 3, and where R is an oxygen atom, characterized in that carry out the acylation derivatives of the formula (II)

in which R4, R5, R6 and R7 have the same meanings as in section 3, and if necessary the compound obtained transformed into a pharmaceutically acceptable salt.

9. The method of obtaining of claim 8, wherein the derivative of formula (II) is obtained from the derivative of formula (III)

by reaction with hydrazine.



 

Same patents:

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of general formula I , in which stands for thiophendiyl, phenylene or pyridindiyl; R1 represents alkyl, alkenyl, alkinyl, which optionally contain one or several substitutes, selected from group including halogen, cyano-, nitro- amino group, -NH-alkyl and N(alkyl)2; or -CH2-(O-CH2-CH2-)mO-alkyl; -(CH2)n-O-alkyl; -(CH2)n-C(O)-NH-alkyl; -(CH2)n-NH-C(O)-alkyl; -(CH2)n-C(O)alkyl; -(CH2)n-C(O)-O-alkyl; or -(CH2)n-O-C(O)-alkyl; or group -NR3R4, in which R3 and R4 independently represent hydrogen; alkyl, alkenyl or alkinyl, which optionally contain one or several substitutes, selected from group including halogen, cyano-, nitro- amino group, -NH-alkyl and N(alkyl) 2; or -CH2-(O-CH2-CH2-)mO-alkyl; -(CH2)n-(O)-alkyl; -(CH2)n-C(O)-NH-alkyl; -(CH2)n-NH-C(O)-alkyl; -(CH2)n-C(O)alkyl; -(CH2)n-C(O)-O-alkyl; or -(CH2)n-O-C(O)-alkyl; n is 1-6; m is 1-4; and to its pharmaceutically acceptable salts. Invention also relates to medication.

EFFECT: obtaining novel biologically active compounds, intended for inhibition tumor cell proliferation.

25 cl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns to new diamides of pyrimidine-4,6-dicarboxylic acid of I formula, selective inhibitors of collagenases possessing properties which concern to the metalloproteinase superfamily and the matrix metalloproteinases. The bonds render influence on hyperactivity of the matrix metalloproteinase-13 (MMP-13) and thus do not render influence on MMP-3 and MMP-8. In the formula I R1 means an atom of hydrogen, R2 means - (C1-C6)-alkyl where alkyl is unitary replaced by phenyl where phenyl is replaced 1) -(C0-C6)-alkyl-C(O)-N(R9)-(R10), where R9 and R10 identical or different and independently from each other mean i) atom of hydrogen or ii) - (C1-C6)-alkyl or R9 and R10 together with atom of nitrogen to which they are bound, form 5, 6-links the sated cycle, and instead of one or two other atoms of carbon there can be also a heteroatom from an oxygen row, sulphur and nitrogen, and in case of nitrogen atoms of nitrogen independently from each other can be unsubstituted or substituted with (C1-C6)-alkyl, 2) -(C0-C6)-alkyl-C(O)-NH-SN, 3) -O-(C0-C6)-alkyl-C(O)-N(R9)-(R10) where R9 and R10 have the specified above value, 4) -(C0-C6)-alkyl-C(O)-N (R8)-(C0-C6)-alkyl-N(R9)-(R10) where R8 means hydrogen, R9 and R10 have the specified above value, 5) -(C0-C6)-alkyl-C(O)-N(R8)-(C0-C6)-alkyl-Het, and R8 has the specified above value, and Het means the sated or nonsaturated monocyclic heterocyclic system with number of links from 3 to 6 which contains in a cycle of 1 or 2 identical or different heteroatoms from a number nitrogen, oxygen and sulphur and unsubstituted or one-, two- or triple independently from each other is replaced by halogen, b) hydroxy,) -(C1-C6)-alkyl, and alkyl is unsubstituted or one-, two- or triple is substituted by halogen, d)=0,e)-Het, R4 and R5 or R5 and R6 together with atom of Carboneum to which they are bound, independently from each other form 5 or 6-unit cycle which is sated and contains one or two heteroatoms from an oxygen row.

EFFECT: obtaining of bonds which can find application for treatment of degenerate diseases of joints, such as osteoarthritis, rheumatic disease.

7 cl, 3 tbl, 117 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention concerns to 3,4-disubstituted tsiklobuten-1,2-diones of the formula I or their pharmaceutically to comprehensible salts or solvates, . A is chosen from the group including

X=-O-, -NH-, -S-,

.

n=1-5

B is chosen from the group including

. The bonds can be used at treatment of mediated chemokine diseases, such as acute both chronic inflammatory diseases and a cancer. The pharmaceutical composition and application of bonds I are also described.

EFFECT: obtaining of bonds which can be used at treatment of mediated chemokine diseases, such as acute both chronic inflammatory diseases and cancer.

50 cl, 31 ex

FIELD: chemistry.

SUBSTANCE: compound of formula I , its diastereomers or salts, where dot line represents optional double bond, m and p independently stand for 0, 1, 2 or 3; R1 stands for H, -N(R8)-C(O)-NR6R7, -N(R8)-S(O)2-NR6R7, -N(R8)-C(O)-N(R8a)-S(O)2-NR6R7, etc.; R1a stands for H or group OH; or R1 or R1a together form oxo; or R1 and R1a together with carbon atom, to which they are bound, form optionally substituted oxo spiro-condensed heterocyclic group, representing fully saturated 5-member monocyclic group, containing 2 nitrogen atoms; R2 stands for heteroaryl, (heteroary)alkyl, representing 5-6-member aromatic ring, contaning 1 nitrogen atom and/or 1 atom of oxygen and/or sulphur, and optionally condensed with aryl ring; aryl, (aryl)alkyl, alkyl, alkenyl or cycloalkyl, representing partly or fully saturated C3-C6 monocyclic structure, any of which can be optionally, independently, substituted with one or more groups T1, T2 or T3; J stands for bond, C1-4 alkylene, R3 stands for -R5, -C(Z1)-R5, -N(R8a1)-C(Z1)-R5, -N(R8a1)-C(Z1)-O-R5, -N(R8a1)-S(O)2-R5; R4 stands for alkyl, halogenalkyl, cycloalkyl, aryl, which can be optionally condensed with heteroaryl 6-member ring, containing 1-2 heteroatoms, selected from group SO2, N, etc.; R5 stands for -NR6aR7a or heteroaryl, (heteroaryl)alkyl, representing 5-6-member aromatic ring, which contains 1-3 nitrogen atoms and/or 1 or 2 atoms of oxygen or sulphur, optionally condensed with heteroaryl ring, representing 6-member aromatic ring, containing 1 nitrogen atom, etc.; R6a, R7a independently represent H, alkyl, aryl, (aryl)alkyl, heteroaryl, representing 5-6-member aromatic ring, which contains 1-2 nitrogen atoms, optionally condensed with aryl or heteroaryl ring, representing 6-member aromatic ring with 1 nitrogen atom; any of which can be optionally, independently, substituted with one or more groups T1c, T2c or T3c; R6, R7, R8, R8a, R8a1 R8a2, and R9, independently, represent H, alkyl, hydroxy, alkoxy, (hydroxy)alkyl, (alkoxy)alkyl, (cyano)alkyl, (alkenyl)alkyl, -NR12R13, cycloalkyl, (cycloalkyl)alkyl, optionally condensed with aryl; aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, etc.; R10, R10a, R11 and R11a, independently, represent H, alkyl, aryl, (aryl)alkyl, , hydroxy, (hydroxy)alkyl; heteroaryl, (heteroaryl)alkyl, representing 5-member aromatic ring, which contains 2 nitrogen atoms, or R11 and R11a can together form oxogroup, or R10a can together with R11a form bond, or R10 can together with R9 form saturated 3-4-member cycle; R12 and R13, independently, represent H, alkyl; W represents =NR8a2, =N- CO2R8a2, =N- CN; X represents C(=O), C=N-CN; Z1represents =O, or =N-CN; RX represents one optional substituent, bound with any suitable carbon atom in cycle, independently selected from T1g, T2g or T3g. Compounds of formula I are applied for manufacturing medication for treatment of IKur-mediated disorders.

EFFECT: cycloalkyl compounds, useful as inhibitors of potassium channels function.

13 cl, 694 ex, 1 tbl

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds of formula (I), its pharmaceutically acceptable salts, possessing qualities of chemokine receptor modulators. Compounds can be applied for asthma, allergic rhinitis, COLD, inflammatory intestinal disease, irritated intestine syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis or cancer. In compound of formula (I) , R1 represents group selected from C1-8alkyl, said group is possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4 , -NR5R6 , phenyl, phenyl is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4,-NR5R6,-SR10,C1-6alkyl and trifluoromethyl; R2 represents group selected from C1-8alkyl, said group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-(C1-6alkyl)-N-(phenyl)amino; R3 represents hydrogen, R4 represents hydrogen or group selected from C1-6alkyl and phenyl, R5 and R6, independently, represent hydrogen or group selected from C1-6alkyl and phenyl, said group being probably substituted with 1, 2 or 3 substituents, independently selected from -OR14, -NR15R16, -COOR14,-CONR15R16, or R5 and R6 together with nitrogen atom, to which they are bound, form 4-7-member saturated heterocyclic ring system, possibly containing additional heteroatom, selected from oxygen and nitrogen atoms, ring possibly being substituted with 1, 2 or 3 substituents, independently selected from -OR14, -COOR14,-NR15R16,CONR15R16 and C1-6alkyl; R10 represents hydrogen or group selected from C1-6alkyl or phenyl; and each from R7, R8, R9, R14, R15, R16 independently represents hydrogen, C1-6alkyl or phenyl; X represents hydrogen, halogeno; Rx represents trifluoromethyl, -NR5 R6 , phenyl, naphtyl, heteroaryl, heteroring can be partly or fully saturated, and one or more ring carbon atoms can form carbonyl group, each phenyl or heteroaryl group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR4, -NR5R6, -CONR5R6, -COR7, -COOR7, -NR8COR9, -SR10, -SO2R10, -SO2NR5R6, -NR8SO2R9, C1-6alkyl or trifluoromethyl; or Rx represents group selected from C1-6alkyl, said group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6, phenyl or heteroaryl, where heteroaryl represents monocyclic or bicyclic aryl ring, containing from 5 to 10 ring atoms, from which 1, 2 or 3 ring atoms are selected from nitrogen, sulfur or oxygen. Invention also relates to methods of obtaining compounds, versions, pharmaceutical composition and application for manufacturing medications using compounds of invention.

EFFECT: obtaining novel compounds of formula (I), its pharmaceutically acceptable salts, possessing properties of chemokine receptor moduators.

25 cl, 138 ex

FIELD: chemistry.

SUBSTANCE: in compound of general formula I or its pharmaceutically acceptable salts or N-oxides R1 stands for , R2 stands for R3 stands for C0-4alkyl.

EFFECT: possibility to use compounds in elaboration of anti-cancer pharmaceutical preparations.

11 cl, 1 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: compounds of formula (I) can be efficient with respect to diseases, in which phosphorylation of Tau protein takes place. , R3 stands for CONR1R2, where R1 and R2 can be substituted with heterocycle; R5, R6, R7 independently on each other are selected from halogen and phenyl; R1, R2 independently on each other stand for hydrogen, (C1-C6)alkyl or together with nitrogen of group CONR1R can form heterocycle.

EFFECT: obtaining novel biologically active compounds.

4 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: in novel compounds of formula (I) X stands for C, N; R1 stands for H or (lower) alkyl, R2 stands for 9(lower) alkyl, -(CH2)n-R2a; R2a stands for C3-C8cycloalkyl, optionally and independently mono-, di-, tri- or tetrasubstituted with the following groups: OH, (lower)alkyl, (lower)alkoxy, 5- or 6-member single-valent saturated heterocyclic ring, containing from one to two heteroatoms, independently selected from nitrogen, oxygen and sulfur, said heterocyclic ring being optionally and independently mono-, di- or tri-substituted with the following groups: OH, (lower)alkyl, (lower)alkoxy, 5- or 6-member single-valent heteroaromatic ring, containing from one to two heteroatoms, independently selected from nitrogen, oxygen and sulfur, said heteroaromatic ring being optionally and independently mono-, di- or tri-substituted with the following groups: OH, (lower) alkyl, (lower)alkoxy, C3-C6cycloalkyl; R3 stands for C3-C6cycloalkyl, being optionally and independently mono-, di- or tri- or tetra-substituted with groups: OH, (lower) alkyl, (lower)alkoxy, phenyl, which optionally and independently is mono-, di- or tri- or tetra-substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, (lower)alkylamino, halogenated (lower)alkyl, halogenated (lower)alkoxy, nitro; R4 stands for 5- or 6-member single-valent heteroaromatic ring, containing from one to two nitrogen heteroatoms, said heteroaromatic ring being optionally and independently mono-, di- or tri- substituted with the following groups: OH, (lower) alkyl, (lower)alkoxy, halogen; naphtyl, which optionally and independently is mono-, di- or tri- substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, (lower)alkylamino, halogenated (lower)alkyl, halogenated (lower)alkoxy, nitro; or phenyl, which optionally and independently is mono-, di- or tri- substituted with groups: OH, (lower)alkyl, (lower)alkoxy, halogen, nitro, halogenated (lower)alkyl, halogenated (lower)alkoxy, cyano, (lower)alkylsulfonyl, -NR7R8; or two neighbouring substituents in said phenyl residue together represent -O-(CH2)p-O-, -(CH2)2-C(O)NH-; R5 and R6 each independently represent H, (lower)alkyl; R7 and R8 each independently represent hydrogen, (lower)alkyl, or R7 and R8 together with nitrogen atom, to which they are bound, form 5- or 6- member saturated or aromatic heterocyclic ring, which optionally contain nitrogen as additional heteroatom; said saturated or aromatic heterocyclic ring, being optionally substituted with the following groups: OH, (lower)alkyl, (lower)alkoxy; m equals 1 or 2, n equals 0 or 1, p equals 1, 2 or 3; or their pharmaceutically acceptable salts.

EFFECT: increased antagonistic activity of compounds.

19 cl

FIELD: chemistry.

SUBSTANCE: in novel substituted aryl ketones of formula (I) Z stands for groupings and A1, A2, A3, R1, R2, R3, R4, R5, R6, R7, X and Y and m are such as given in formula of invention. In substituted aryl carboxylic acid of formula (II) and derivative of aryl carboxylic acid of formula (III) A1, A2, A3, R1, R2, X and Y are such as given in item 1 of invention formula, R12 stands for allyl, which are intermediate products. Also described is means to fight undesirable plants based on formula (I) compound.

EFFECT: increased herbicidal activity.

7 cl, 3 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to acidylated heteroarylcondensed cycloalkenylamines with formula I in any of their stereoisomeric form or in form of their mixtures in any ratio, or their pharmaceutical salts, where in formula I: ring A represents an aromatic 6-member ring, containing 1 nitrogen atom, or a 5-member aromatic ring, containing 1 sulphur atom; one or two of R1, R2, R3 and R4 is independently chosen from a group consisting of hydrogen, halogen or C1-C4-alkyl, and the other R1, R2, R3 and R4 represent hydrogen; R5 represents an Ar group or Hetar group. Description is also given of a pharmaceutical composition based on compound with formula I and use of the latter.

EFFECT: regulation of the expression of the enzyme endothelial NO-synthesis.

10 cl, 31 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention claims ethers of substituted 1H-indol-3-carboxylic acid of the general formula 1 or their pharmaceutically acceptable salts. Compounds can be applied as active substance for pharmaceutical compositions and for application of these compositions in production of medicine for virus disease prevention and treatment, especially for diseases caused by infection hepatitis viruses (HCV, HBV) and influenza A viruses. In the general formula 1 R1 is aminogroup substitute selected out of hydrogen, optionally substituted inferior alkyl, optionally substituted C3-6cycloalkyl, optionally substituted aryl selected out of phenyl, naphthyl or 5-6 member heteroaryl containing 1-2 heteroatoms selected out of nitrogen, oxygen and sulfur, and possibly condensed with benzene ring of optionally substituted heterocyclyl, which can be optionally substituted 5-6-member heterocyclyl with 1-2 heteroatoms in heterocyclic ring selected out of nitrogen and oxygen; R2 is alkyl substitute selected out of hydrogen, optionally substituted hydroxyl group, optionally substituted mercapto group, optionally substituted arylsulfinyl group; optionally substituted amino group, optionally substituted 5-6-member heterocyclyl containing 1-2 heteroatoms selected out of nitrogen, oxygen and sulfur; R3 is hydrogen or optionally substituted inferior alkyl; R14 and R24 are independently substitutes of cyclic system, selected out of hydrogen or halogen atom, cyano group, trifluoromethyl, optionally substituted phenyl or optionally substituted heterocyclyl which is an optionally substituted 5-6-member heterocyclyl with 1-2 heteroatoms in heterocyclic ring, selected out of nitrogen, oxygen or sulfur, possibly condensed with benzene ring.

EFFECT: improved efficiency of compositions.

15 cl, 3 tbl, 1 dwg, 6 ex

FIELD: medicine.

SUBSTANCE: present invention concerns application of new biologically active substances of the general formula of 1 either their racemates, or their optical isomers, or their pharmaceutically comprehensible salts and-or hydrates, and also to a pharmaceutical composition and its use at manufacturing of the medicinal preparations applied to treatment and-or preventive maintenance of diseases, caused by flu viruses. In compounds of the general formula 1, R1 are represented by the substituent to the amino group chosen from unessentially replaced C1-C6alkyl, unessentially replaced aryl or unessentially replaced 5-6 term azaheterocycl, R14 and R24 independently from each other represent the substituent to an amino group chosen from hydrogen, unessentially replaced C1-C6alkyl, unessentially replaced C3-C8cycloalkyl, or R14 and R24, together with atom of nitrogen to which they are bound, form through R14 and R24 unessentially replaced 5-6-term azaheterocycl with 1-3 heteroatoms in a ring and which can be monocyclic or condensed with a benzene ring, or aminoethanamidine; R2 is a substituent chosen from hydrogen, of unessentially replaced mercapto group, unessentially replaced amino group, unessentially replaced hydroxyl represents alkyn; R3 represents the lowest alkyl; R5 the substituent to the cyclic system chosen from hydrogen, atom of halogen, cyano group, unessentially replaced aryl or unessentially replaced 5-6-term heterocycl represents, the containing 1-2 heteroatoms chosen from nitrogen, oxygen or sulphur and which can be monocyclic or condensed with a benzene ring.

EFFECT: invention provides increase of efficiency of a composition and a method of treatment.

11 cl, 1 dwg, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the compound of formula I: , where R1, R2 and R3 are equal or different and represent hydrogen, halogen, alkyl, aloxy, hydroxyl, nitro, amino, alkylcarbonylamino, alkylamino or dialkylamino group, R4 represents hydrogen, alkyl or alkylaryl group; X represents CH2, oxygen atom and sulphur atom; n represents 2 or 3, and individual (R)- and (S)-enantiomers or the mixture of enantiomers and its pharmaceutically acceptable salts; where alkyl termine denotes straight and branched hydrocarbon chains, containing fro one to six atoms of carbon, optionally substituted by aryl, alkoxy, halogen, alkoxycarbonyl or hydroxycarbonyl groups, termine aryl denotes phenyl or naphtyl group, optionally substituted alkyloxy group, halogen or nitro group, termine halogen denotes fluorine, chlorine, bromine or iodine. The compounds have valuable pharmaceutical properties and perspectives for the treatment of cardiovascular disorder, such as hypertension and chronic heart failure. The method of production of individual (R)- and (S)-enantiomers or the mixture of enantiomers and pharmaceutically acceptable salts of the compound of formula I, pharmaceutical composition having inhibitor dophamine-β-hydrolaze potency, containing therapeutic effective volume of the compound of formula I, different variants of formula I compound application and intermediate compounds are described.

EFFECT: production of new compounds, imidazole derivatives having useful biological properties.

21 cl, 2 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of benzimidazol of the general formula I R1 designates phenyl group which unessentially contains up to three substitutors independently chosen of the group including F, Cl, Br, J, R4; R2 designates monocyclic or bicyclic 5-10-terms heteroaryl group which contains 1-2 heteroatoms, chosen of N, S and O; R3 designates H; R4 designatesC1-6alkyl; A designates C2-6 alkylene group; B designates group COOH, CONH2, CONHR5 or CONR5R5, in each case attached to atom of carbon of group A; R5 and R5 ' independently designate the residue chosen from group includingC1-6 alkyl where one C-atom can be replaced by O, and(C0-3 alkandiil-C3-7 cycloalkyl); and to their pharmaceutically acceptable salts, except for following compounds: 6 [[1-phenyl-2 (pyridine-4-il)-1H-benzimidazol-6-il] oxi] hexanic acid and 6 [[1-phenyl-2 (benzothien-2-il)-1H-benzimidazol-6-il] oxi] hexanic acid. The invention relates also to pharmaceuticals and to application of compounds of general formula I.

EFFECT: new biologically active compounds possess inhibiting effect on activation of microglia.

10 cl, 34 ex

FIELD: organic chemistry, medicine, pharmacy, chemical technology.

SUBSTANCE: invention relates to novel substituted esters of 1H-indol-3-carboxylic acids of the general formula (1): or their racemates, or their optical isomers, or their pharmaceutical acceptable salts and/or hydrates. Compounds can be used in treatment of such diseases as infectious hepatitis, human immunodeficiency, atypical pneumonia and avian influenza. In compound of the general formula (1) R1, R41 and R42 each represents independently of one another a substitute of amino group chosen from hydrogen atom, optionally linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and possibly an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 carbon atom in ring with one or some heteroatoms chosen from nitrogen oxygen or sulfur atoms; or R41 and R42 in common with nitrogen atom to which they are bound form 5-10-membered azaheterocycle or guanidyl through R41 and R42; R2 represents an alkyl substitute chosen from hydrogen atom, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl; R5 represents a substitute of cyclic system chosen from hydrogen atom, halogen atom, cyano group, optionally substituted aryl or optionally substituted and possibly an annelated heterocycle that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms. Also, invention relates to methods for treatment, drugs and pharmaceutical compositions using compounds of this invention.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of synthesis.

22 cl, 3 tbl, 8 dwg, 6 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to a compound of the formula (I): , wherein carbon atom designated as * is in (R)- or (S)-configuration; R1 represents (C1-C6)-alkyl; R2 represents hydrogen atom (H), (C1-C6)-alkyl or (C1-C6)-halogenalkyl; R3 represents H or halogen atom; R4 represents phenyl, naphthyl, pyridyl, pyridazinyl, pyrimidinyl, furanyl, thienyl, thiazolyl, isoxazolyl, pyrazolyl or pyrazinyl wherein R4 group is substituted optionally with 1-4 R14-substitutes; each among R5, R6 and R7 is chosen independently from the following group: H, halogen atom, -OR11, -CN, (C1-C4)-halogenalkyl or (C1-C6)-alkyl; or R5 and R6 taken in common can represent -O-C-(R12)2-O-; R8 represents H; R11 represents H or (C1-C4)-alkyl; R12 represents (C1-C4)-alkyl; R12 is chosen independently in each case from a substitute chosen from the following group: halogen atom, -OR11, -NR11R12, morpholinyl, (C1-C6)-alkyl and (C1-C4)-halogenalkyl, or its pharmaceutically acceptable salt or solvate. Also, invention describes a pharmaceutical composition used in blocking in reuptake of norepinephrine, dopamine and serotonin based on compounds of the formula (I). Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties, improved method of treatment.

39 cl, 2 tbl, 49 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to group of novel derivatives of 4,5-dihydro-1H-pyrazole and their stereoisomers that are strong antagonists of cannabinoid (CB1) receptors. These compounds are useful in treatment of some diseases associated with cannabinoid system disorders. Compounds have the general formula (I) wherein R represents phenyl or thienyl substituted with halogen atom, or R represents pyridyl; R1 represents phenyl that can be substituted with 1-2 substitutes chosen from halogen atom and trifluoromethyl group; R2 represents hydrogen atom; R3 represents hydrogen atom or branched or direct (C1-C4)-alkyl group; R4 represents branched or direct (C2-C4)-alkyl group that is substituted with hydroxy-, amino-, monoalkylamino-, dialkylamino-, methoxy-, acetoxy-, aminooxy-group or one fluorine atom, or R4 represents branched or direct (C1-C8)-alkoxy-group that can be substituted with amino-group, monoalkylamino-group or dialkylamino-group, or R4 represents (C4-C8)-nonaromatic heterocyclic or (C4-C8)-nonaromatic heterocycloalkyl-alkyl group that comprise 1-2 heteroatoms chosen from nitrogen (N) and oxygen (O) atom that can be substituted with (C1-C3)-alkyl group, or R4 represents hydroxy-group or imidazolylalkyl group or pyridylmethyl group; or if R represents hydrogen atom or methyl then R4 can represent group -NR6R7 wherein R6 represents hydrogen atom and R7 represents (C2-C4)-trifluoroalkyl; or R3 and R4 in common with nitrogen atom to which they are bound form saturated or unsaturated monocyclic or bicyclic heterocyclic group comprising 4-10 atoms in cycle that comprises 1-2 heteroatoms chosen from N and O, or group -SO2 wherein indicated group can be substituted with (C1-C4)-alkyl, hydroxy-group, hydroxyalkyl, pyridyl, amino-, monoalkylamino-, dialkylamino-group, monoalkylaminoalkyl, dialkylaminoalkyl or piperidyl group; R5 represents phenyl group substituted with 1-3 substitutes Y wherein Y represents halogen atom, trifluoromethyl group or (C1-C3)-alkyl, or R5 represents branched or direct (C1-C8)-alkyl. Also, invention relates to pharmaceutical compositions containing one or some these compounds as an active component.

EFFECT: valuable biological and medicinal properties of compounds and pharmaceutical compositions.

5 cl, 4 tbl, 92 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of thiophene of the general formula (I): , wherein R1 is chosen from group consisting of hydrogen atom (H), -C(O)R7, -CO2R7, -C(O)NR7R8, -C(O)N(R7)OR8, -C(O)N(R7)-R2-OR8, -C(O)N(R7)-Ph, -C(O)N(R7)-R-Ph, -C(O)N(R7)S(O)2R8, -R2-OR7, -R2-O-C(O)R7, -C(S)R7, -C(S)NR7R8, -C(S)N(R7)-Ph, -C(S)N(R7)-R2-Ph, -R2-SR7, -CN, -OR7 and Het wherein Het represents tetrazolyl; Q1 represent group of the formula: -(R2)a-(Y1)b-(R2)c-R3 wherein a, b and a are similar or different and each means independently 0 or 1, and at least one among a or b means 1; n means 0, 1, 2, 3 or 4; Q2 represents group of the formula: -(R2)aa-(Y2)bb-(R2)cc-R4, or two adjacent Q2 groups represent -OR7 and in common with carbon atoms to which they are bound form 5-7-membered heterocycle comprising 1 or 2 heteroatoms chosen from oxygen atom (O); R5 is chosen from group consisting of H, alkyl and -NR7R8, or their pharmaceutically acceptable salts and solvates. Compounds can be used in treatment of states mediated by Polo-like kinase and sensitive neoplasm. Also, invention describes a method for synthesis of these compounds and preparing pharmaceutical compositions based on thereof.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

27 cl, 1 tbl, 199 ex

FIELD: organic chemistry, chemical technology, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): and their pharmaceutically acceptable salts possessing inhibitory effect on activity of dipeptidyl peptidase IV (DPP IV) that can be used, for example, in treatment of diabetes mellitus type 2. In compounds of the formula (I) X means nitrogen atom (N) or -C-R5; R1 and R2 mean independently hydrogen atom, (C1-C6)-alkyl; R3 means saturated or aromatic 5-7-membered heterocyclyl comprising 1-2 heteroatoms chosen from nitrogen, sulfur and oxygen atoms, possibly condensed with 1-2 benzene rings, saturated or aromatic 5-7-membered heterocyclyl comprising 1-2 heteroatoms chosen from nitrogen, sulfur and oxygen atoms, possibly condensed with 1-2 benzene rings, mono-, di- or tri-substituted independently with (C1-C6)-alkyl, (C1-C6)-alkoxy-group, perfluoro-(C1-C6)-alkyl or halogen atom, phenyl, naphthyl, phenyl or naphthyl mono-, di- or tri-substituted independently with halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, or perfluoro-(C1-C6)-alkyl; R4 means (lower)-alkyl, (lower)-alkoxy-, (lower)-alkylthio-group, saturated or aromatic 7-7-membered heterocyclyl comprising 1-2 heteroatoms chosen from nitrogen, sulfur and oxygen atoms, possibly condensed with 1-2 benzene rings, saturated or aromatic 5-7-membered heterocyclyl comprising 1-2 heteroatoms chosen from nitrogen, sulfur and oxygen atoms, possibly condensed with 1-2 benzene rings mono-, di- or tri-substituted independently with (C1-C6)-alkyl, (C1-C6)-alkoxy-group, perfluoro-(C1-C6)-alkyl or halogen atom, phenyl, naphthyl, phenyl or naphthyl mono-, di- or tri-substituted independently with halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-, amino-group or perfluoro-(C1-C6)-alkyl, 4-fluorophenyloxy-(C1-C6)-alkyl or (C3-C6)-cycloalkyl; R5 means hydrogen atom or (C1-C6)-alkyl. Also, invention relates to methods for synthesis of compounds of the formula (I), pharmaceutical compositions and their using for preparing medicaments used in treatment and/or prophylaxis of DPP IV-mediated diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of synthesis.

21 cl, 93 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns to new diamides of pyrimidine-4,6-dicarboxylic acid of I formula, selective inhibitors of collagenases possessing properties which concern to the metalloproteinase superfamily and the matrix metalloproteinases. The bonds render influence on hyperactivity of the matrix metalloproteinase-13 (MMP-13) and thus do not render influence on MMP-3 and MMP-8. In the formula I R1 means an atom of hydrogen, R2 means - (C1-C6)-alkyl where alkyl is unitary replaced by phenyl where phenyl is replaced 1) -(C0-C6)-alkyl-C(O)-N(R9)-(R10), where R9 and R10 identical or different and independently from each other mean i) atom of hydrogen or ii) - (C1-C6)-alkyl or R9 and R10 together with atom of nitrogen to which they are bound, form 5, 6-links the sated cycle, and instead of one or two other atoms of carbon there can be also a heteroatom from an oxygen row, sulphur and nitrogen, and in case of nitrogen atoms of nitrogen independently from each other can be unsubstituted or substituted with (C1-C6)-alkyl, 2) -(C0-C6)-alkyl-C(O)-NH-SN, 3) -O-(C0-C6)-alkyl-C(O)-N(R9)-(R10) where R9 and R10 have the specified above value, 4) -(C0-C6)-alkyl-C(O)-N (R8)-(C0-C6)-alkyl-N(R9)-(R10) where R8 means hydrogen, R9 and R10 have the specified above value, 5) -(C0-C6)-alkyl-C(O)-N(R8)-(C0-C6)-alkyl-Het, and R8 has the specified above value, and Het means the sated or nonsaturated monocyclic heterocyclic system with number of links from 3 to 6 which contains in a cycle of 1 or 2 identical or different heteroatoms from a number nitrogen, oxygen and sulphur and unsubstituted or one-, two- or triple independently from each other is replaced by halogen, b) hydroxy,) -(C1-C6)-alkyl, and alkyl is unsubstituted or one-, two- or triple is substituted by halogen, d)=0,e)-Het, R4 and R5 or R5 and R6 together with atom of Carboneum to which they are bound, independently from each other form 5 or 6-unit cycle which is sated and contains one or two heteroatoms from an oxygen row.

EFFECT: obtaining of bonds which can find application for treatment of degenerate diseases of joints, such as osteoarthritis, rheumatic disease.

7 cl, 3 tbl, 117 ex

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