Aminothiazole inhibitors of cyclin-dependent kinase

 

The invention relates to new derivatives of aminothiazole formula I and their pharmaceutically acceptable salts, where R1and R2independently of one another denote hydrogen, fluorine or lower alkyl; R3denotes heteroaryl selected from oxazolyl, which is substituted by one or more substituents selected from lower alkyl, halogen, carbamoyl, allyloxycarbonyl, alkylcarboxylic; or benzoxazole; R4denotes hydrogen;-alkyl which can be optionally substituted with halogen, alkoxy, hydroxy, allyloxycarbonyl, alkylcarboxylic, amino, carbamoyl; CO-cycloalkyl; CO-aryl, where aryl represents phenyl which may be optionally substituted with halogen, lower alkyl, alkoxy, amino, cyano or naphthyl, and so on; or COO-alkyl; COO-cycloalkyl; soo-phenyl; COO-alkyl-phenyl; SO2-alkyl; SO2-phenyl, C(NCN)NH-phenyl, where phenyl may be optionally substituted with halogen; R5denotes hydrogen; m is an integer from 0 to 2; n is 0. Pharmaceutical composition having the effect of an inhibitor of protein kinase containing a compound of formula I and a pharmaceutically acceptable carrier. Pharmaceutical composition having an action inhibant. The method of inhibition of cyclin-dependent kinase, comprising the administration to a mammal in need, an effective amount of the compounds of formula I. the Technical result - obtaining new derivatives isothiazolinones acid. 17 C. and 9 C.p. f-crystals, 2 PL.

Description text in facsimile form (see graphic part). T Those

Claims

1. Connection aminothiazole formulaand their pharmaceutically acceptable salts, where R1and R2independently of one another denote hydrogen, fluorine or lower alkyl; R3denotes heteroaryl selected from oxazolyl, which may be substituted by one or more substituents selected from lower alkyl, halogen, carbamoyl, alkoxycarbonyl, alkylcarboxylic; or benzoxazole; R4denotes hydrogen, alkyl which may be optionally substituted with halogen, alkoxy, hydroxy, alkoxycarbonyl, alkylcarboxylic, amino, carbamoyl; CO-cycloalkyl; CO-aryl, where aryl represents phenyl which may be optionally substituted with halogen, lower alkyl, alkoxy, amino, piano or naphthyl; CO-halogeno, lower alkyl, alkoxy, hydroxy, carboxy, trifluoromethyl, amino or naphthyl; WITH heteroaryl where heteroaryl represents furyl, pyrrolyl, pyridinyl, imidazolyl, pyrrolidinyl, oxazolyl, pyrazolyl, pyrazinyl, indolyl, isoindolyl, chinoline, benzothiazolyl, benzimidazolyl; CO-alkylglycerol where heteroaryl is thienyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl, pyrimidinyl, indolyl, isoindolyl, chinoline, benzothiazolyl, benzoxazolyl; CO-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic nitrogen-containing ring; CONH-alkyl, where alkyl optionally may be substituted by alkoxy, hydroxy; CONH-cycloalkyl, CONH-phenyl, where phenyl may be optionally substituted with halogen, lower alkyl, alkoxy, carbamoyl, amino; CONH-alkyl-cycloalkyl; CONH-alkyl-phenyl, where phenyl may be optionally substituted with halogen, lower alkyl, alkoxy; CONH-heteroaryl where heteroaryl represents pyridinyl, triazolyl, pyrazolyl, isoxazolyl, chinoline, benzothiazolyl; CONH-alkyl-heteroaryl where heteroaryl represents furyl, thienyl, pyridinyl, pyrimidinyl, imidazolyl, indolyl; CONH-heteroseksualci where heteroseksualci is a 5-6-membered neurom the sludge; SO2is phenyl; C(NN)NH-phenyl, where phenyl may be optionally substituted with halogen; R5denotes hydrogen; m is an integer from 0 to 2; n is 1.

2. Connection on p. 1, wherein R1and R2denote independently hydrogen, fluorine or lower alkyl; R3does

where Y denotes oxygen;
R4denotes hydrogen, alkyl which may be optionally substituted with halogen, alkoxy, hydroxy, alkoxycarbonyl, alkylcarboxylic, amino, carbamoyl; CO-cycloalkyl; CO-aryl, where aryl represents phenyl which may be optionally substituted with halogen, lower alkyl, alkoxy, amino, cyano or naphthyl; CO-alkyl-cycloalkyl; CO-alkyl-aryl, where aryl represents phenyl which may be optionally substituted with halogen, lower alkyl, alkoxy, hydroxy, carboxy, trifluoromethyl, amino or naphthyl; CO-heteroaryl where heteroaryl represents furyl, pyrrolyl, pyridinyl, imidazolyl, pyrrolidinyl, oxazolyl, pyrazolyl, pyrazinyl, indolyl, isoindolyl, chinoline, benzothiazolyl, benzimidazolyl; CO-alkylglycerol where heteroaryl is thienyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl, cloaker is a 5-6-membered non-aromatic nitrogen-containing ring; CONH-alkyl, where alll optionally may be substituted by alkoxy, hydroxy; CONH-cycloalkyl, CONH-phenyl, where phenyl may be optionally substituted with halogen, lower alkyl, alkoxy, carbamoyl, amino; CONH-alkyl-cycloalkyl; CONH-alkyl-phenyl, where phenyl may be optionally substituted with halogen, lower alkyl, alkoxy; CONH-heteroaryl where heteroaryl represents pyridinyl, triazolyl, pyrazolyl, isoxazolyl, chinoline, benzothiazolyl; CONH-alkyl-heteroaryl where heteroaryl represents furyl, thienyl, pyridinyl, pyrimidinyl, imidazolyl, indolyl; CONH-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic N - or O-containing ring; or COO-alkyl; COO-cycloalkyl; soo-phenyl; COO-alkyl-phenyl; or SO2-alkyl; SO2is phenyl; C(NN)NH-phenyl, where phenyl may be optionally substituted with halogen;
R5denotes hydrogen;
R7and R8independently represent hydrogen, lower alkyl;
m denotes an integer from 0 to 2;
n is 1.

3. Connection on p. 1, wherein R1and R2denote independently hydrogen, fluorine or lower alkyl; R3does

where Y denotes oxygen;
R4indicates Anilox, amino, carbamoyl; CO-cycloalkyl; CO-alkyl-aryl, where aryl represents phenyl which may be optionally substituted with halogen, lower alkyl, alkoxy, hydroxy, carboxy, trifluoromethyl, amino or naphthyl; CO-alkyl-heteroaryl where heteroaryl is thienyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl, pyrimidinyl, indolyl, isoindolyl, chinoline, benzothiazolyl, benzoxazolyl; CO-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic nitrogen-containing ring; CONH-heteroseksualci, where heteroseksualci is a 5-6-membered non-aromatic N - and O-containing ring; CONH-alkyl, where alkyl optionally may be substituted by alkoxy, hydroxy; CONH-alkyl-phenyl, where phenyl may be optionally substituted with halogen, lower alkyl, alkoxy, and CONH-cycloalkyl;
R5denotes hydrogen;
R7and R8represent hydrogen;
m is 0;
n is 1.

4. Connection on p. 1, wherein R1and R2denote independently hydrogen, fluorine or lower alkyl; R3does

where Y denotes oxygen;
R4means CO-alkyl, which may be optionally substituted with halogen, aaryl represents phenyl, which may be optionally substituted with halogen, lower alkyl, alkoxy, hydroxy, carboxy, trifluoromethyl, amino or naphthyl; CO-alkyl-heteroaryl where heteroaryl is thienyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl, pyrimidinyl, indolyl, isoindolyl, chinoline, benzothiazolyl, benzoxazolyl; CO-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic nitrogen-containing ring; CONH-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic N - and O-containing ring; CONH-alkyl, where alkyl optionally may be substituted by alkoxy, hydroxy; CONH-alkyl-phenyl, where phenyl may be optionally substituted with halogen, lower alkyl, alkoxy, and CONH-cycloalkyl;
R5denotes hydrogen;
R7and R8denote alkyl;
m is 0;
n is 1.

5. Connection on p. 1, wherein R1and R2denote independently hydrogen, fluorine or lower alkyl; R3does

where Y denotes oxygen;
R4means CO-alkyl, which may be optionally substituted with halogen, alkoxy, hydroxy, alkoxycarbonyl, alkylcarboxylic, amino, carbamoyl;-cyclea slim-alkyl, alkoxy, hydroxy, carboxy, trifluoromethyl, amino or naphthyl; CO-alkyl-heteroaryl where heteroaryl is thienyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl, pyrimidinyl, indolyl, isoindolyl, chinoline, benzothiazolyl, benzoxazolyl; CO-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic nitrogen-containing ring; CONH-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic N - and O-containing ring; CONH-alkyl, where alkyl optionally may be substituted by alkoxy, hydroxy; CONH-alkyl-phenyl, where phenyl may be optionally substituted with halogen, lower alkyl, alkoxy, and CONH-cycloalkyl;
R5denotes hydrogen;
R7denotes hydrogen;
R8denotes alkyl;
m is 0;
n is 1.

6. Connection on p. 1, wherein R1and R2denote independently hydrogen, fluorine or lower alkyl; R3does

where Y denotes oxygen;
R4means CO-alkyl, which may be optionally substituted with halogen, alkoxy, hydroxy, alkoxycarbonyl, alkylcarboxylic, amino, carbamoyl; CO-cycloalkyl; CO-alkyl-aryl, where aryl is Soboh what tormation, amino or naphthyl; CO-alkyl-heteroaryl where heteroaryl is thienyl, pyridinyl, imidazolyl, thiazolyl, oxazolyl, pyrimidinyl, indolyl, isoindolyl, chinoline, benzothiazolyl, benzoxazolyl; CO-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic nitrogen-containing ring; CONH-heteroseksualci where heteroseksualci is a 5-6-membered non-aromatic N - and O-containing ring; CONH-alkyl, where alkyl optionally may be substituted by alkoxy, hydroxy; CONH-alkyl-phenyl, where phenyl may be optionally substituted with halogen, lower alkyl, alkoxy, and CONH-cycloalkyl;
R5denotes hydrogen;
R7denotes alkyl;
R8denotes hydrogen;
m is 0;
n is 1.

7. Connection on p. 1, characterized in that it is a
N-[5-[[(5-ethyl-2-oxazolyl)methyl] thio] -2-thiazolyl] ndimethylacetamide;
N-[5-[[(5-ethyl-2-oxazolyl)methyl] thio] -2-thiazolyl] benzamide;
N-[5-[[(5-ethyl-2-oxazolyl)methyl] thio] -2-thiazolyl] benzosulfimide;
N-[5-[[(4,5-dimethyl-2-oxazolyl)methyl] thio] -2-thiazolyl] ndimethylacetamide;
N-[5-[[(5-tert. butyl-2-oxazolyl)methyl] thio] -2-thiazolyl] ndimethylacetamide;
N-[5-[[(5-tert. butyl-2-oxazolyl)methyl] thio] -2-thiazolyl] trimethylacetamido;
N-[5-[[(4-ethyl-2-oxaz the tion, with the action of the inhibitor of protein kinase containing a derivative of thiazole and a pharmaceutically acceptable carrier, characterized in that it contains as derived thiazole compound under item 1.

9. Pharmaceutical composition having the effect of an inhibitor of protein kinase containing a derivative of thiazole, pharmaceutically acceptable carrier and an anti-cancer agent, characterized in that it contains as derived thiazole compound under item 1 in the form of a fixed dosage forms.

10. The pharmaceutical composition according to p. 8 containing a connection on p. 1 in combination with a pharmaceutically acceptable carrier used in combination with anti-cancer treatment or in combination with an anticancer agent, the input sequence.

11. The pharmaceutical composition according to p. 10, characterized in that the specified combination, including the connection specified under item 1 and the specified pharmaceutically acceptable carrier, entered before applying anti-cancer treatment or anti-cancer agent.

12. The pharmaceutical composition according to p. 8, characterized in that the specified combination, including the connection specified under item 1 and the pharmaceutically acceptable carrier is introduced after proteinkinase, includes introduction to the mammal in need of this, the effective number of connections on p. 1.

14. The method of inhibition of cyclin-dependent kinase, comprising the administration to a mammal in need, an effective amount of the compounds under item 1.

15. The method of inhibiting cdc2 (cdk1), including introduction to a mammal in need, an effective amount of the compounds under item 1.

16. The method of inhibiting cdk2, including the introduction to a mammal in need, an effective amount of the compounds under item 1.

17. Method of inhibiting cdk3, including the introduction to a mammal in need, an effective amount of the compounds under item 1.

18. Method of inhibiting cdk4, including the introduction to a mammal in need, an effective amount of the compounds under item 1.

19. Method of inhibiting cdk5, including the introduction to a mammal in need, an effective amount of the compounds under item 1.

20. How cdk6 inhibition, comprising the administration to a mammal in need, an effective amount of the compounds under item 1.

21. Method of inhibiting cdk7, including the introduction to a mammal in need, an effective amount of the compounds under item 1.

22. Spontania by p. 1.

23. A method of treating proliferative diseases comprising administration to a mammal in need, a therapeutically effective amount of the composition under item 8.

24. A method of treating cancer, comprising the administration to a mammal in need, a therapeutically effective amount of the composition under item 8.

25. A method of treating proliferative diseases comprising administration to a mammal in need, a therapeutically effective amount of the composition under item 9.

26. A method of treating proliferative diseases comprising administration to a mammal in need, a therapeutically effective amount of the composition of p. 10.

 

Same patents:

The invention relates to amino acid derivatives of the formula I

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or its non-toxic salt or its hydrate, the pharmaceutical composition having inhibitory effect on calcium channel iv-type; the inhibitor calcium channel N-type; a pharmaceutical composition for prevention and/or treatment of cerebral infarction and pharmaceutical compositions for the treatment of pain

The invention relates to a derivative of sulfoaluminate and sulphoniumhydroxide acid of formula I, its pharmaceutically acceptable salts, where W is-HE-or-NHOH; X denotes (a) a heterocyclic radical selected from the group comprising imidazolines, dihydrobenzofuranyl and so on, b) -NR1SO2R2where R1denotes a hydrogen atom, R2denotes an unsubstituted phenylalkyl and so on; Y represents carbon or sulfur, with the proviso that when Y represents carbon, n is equal to 2; Z represents phenyl, optionally substituted with halogen, unsubstituted alkoxy, phenyloxy, optionally substituted with halogen, phenylacetonitrile, 4-methylpiperazine, 4-phenylpiperidine, pyridyloxy, -NR'1COR'2, -SO2R'2where R'1denotes a hydrogen atom, R'2denotes phenyl, optionally substituted by hydroxy or phenyl, pyridinyl, substituted-CF3; m denotes an integer from 1 to 4, n represents an integer of 1 or 2

The invention relates to new cyclic diamine compounds of the formula I, where

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represents an optionally substituted divalent residue of benzene, where the substituents are selected from unsubstituted lower alkyl groups, unsubstituted lower alkoxygroup, unsubstituted lower acyl group, a lower allylthiourea, lower alkylsulfonyl group, halogen atom, etc. or unsubstituted pyridine; Ar represents a phenyl group which may be substituted by one to four groups selected from unsubstituted lower alkyl group, the unsubstituted alkoxygroup, low allylthiourea, lower alkylsulfonyl group, and so on, optional substituted amino group, alkylenedioxy; X is-NH-, oxygen atom or sulfur atom; Y is a sulfur atom, sulfoxide or sulfon; Z represents a single bond or-NR2-; R2- the atom of hydrogen or unsubstituted lower alkyl group; l = 2 or 3; m = 2 or 3; n = 1, 2, or 3, or their salts, or their solvate

The invention relates to new derivatives isothiazolinones acid of the formula I, where R stands for a group-OR1or-SR2in which R1means alkyl with 1-6 carbon atoms, a substituted once residues selected from the group comprising halogenoalkanes with 1-6 carbon atoms and 1 to 5 halogen atoms, dialkylamino with 1-6 carbon atoms in each alkyl part, phenylalkyl with 1-4 carbon atoms in the CNS parts and pyrrolidinyloxyl with 1-4 carbon atoms in the CNS part, and twice by hydroxyl, or so, m and n is 2, R3means phenyl, R4means alkyl with 1-4 carbon atoms, R2means alkyl with 1-6 carbon atoms, or R2means phenylalkyl with 1-2 carbon atoms in the alkyl part, with the phenyl portion may be substituted with halogen

The invention relates to a new derivative of solidilin formula (I) where one of X, Y and Z represents C=O or C=S, and one of the remaining X, Y and Z denotes a group With=, and the other group C=S; R1, R2and R3are Deputy or X, Y and Z, or nitrogen atom and may be the same or different and denote hydrogen, halogen, hydroxy, nitro, etc., the group -(CH2)n-O - and may be joined through the nitrogen atom, or X, Y, Z, n is 1-4, Ar denotes a phenylene or naftilan, R4denotes hydrogen or forms a bond with group a, And denotes nitrogen or CR5, R5denotes hydrogen, halogen or forms a bond with R4In means O or S, when a is CR5and means that, when a is N, its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salt and solvate

The invention relates to the derivatives of propanolamine formula (I) and their pharmaceutically acceptable salts, where R1and R2means phenyl, naphthyl, pyridyl, thienyl, pyrimidyl, thiazolyl, hinely, piperazinil, oxazolyl, which may be substituted with halogen, HE, NO2, NH2, COOH, etc., R3-R8mean hydrogen, hydroxyl, (C1-C8-alkoxy, NH2-THE OTHER9, -N(R9R10, R9-R10mean hydrogen or (C1-C8)alkyl, X is CH or N, Y represents CH or N, provided that the residues R1, R2X and Y are not simultaneously mean R1- phenyl, R2is phenyl, X is CH, Y is CH

The invention relates to the derivatives of pyrrolidine formula I

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where R1- H, C1-C6alkyl; phenyl, possibly substituted; biphenyl, possibly substituted; 1H, 5H - pyrido [3,2,1-ij] chinolin; phenyl WITH1-C6alkyl, optionally substituted; biphenyl WITH1-C6alkyl, optionally substituted; biphenylcarboxylic; terphenyl; naphthyl, optionally substituted; Z denotes-S-, -O-, -och2-, -N(R16), where R16- H, C1-C6alkyl, C3-C8cycloalkyl1-C6alkyl, panels1-C6alkyl, a chemical bond; X1means-CO-, -(CH2)r-CO-N(R17), where R17means H, C1-C6alkyl (where r = 0 or 1), -CH2NHSO2-, -(CH2)s-N (R18)-CO- (where R18- N, s=1-3), - CH2NHCОСН2O-, -CH2N (R19Of PINES = CH- (where R19- H, -CH2OCH2-, -CH2-N (R20)-CH2- (where R20- H, C1-C6alkyl, C1-C6alkylsulphonyl, phenylcarbinol)1-C5alkylen,2-C4albaniles, a chemical bond; X2- phenylene, optionally substituted hydroxy, theoffender, purandar, piperidinyl,< / BR>
< / BR>
< / BR>
R2and R3each - H; and R4- phenyl, possibly substituted with halogen; R5- phenyl, possibly substituted; a cycle of G is phenyl,3-C7cycloalkyl, pyridyl, thienyl; loop J is phenyl; L is phenyl; p=0-2;----- means the presence or absence of chemical bonding;displays a CIS - or TRANS-configuration D relative to E; provided that X1means-CH2NHCО-, X2means 1,4-phenylene and X3means a chemical bond or a C1-C5alkylen, when the carbon atom bound CD and adjacent carbon atom in the cycle are connected by a simple relation and V1does not mean a chemical bond, when X1means-CH2O-; and pharmaceutically acceptable salt or hydrate of the compound

The invention relates to new heterocyclic compounds of the formula (I), where R1represents a group of formula (II), R is 2,4-dioxothiazolidine-5-ylmethylene group and others, And represents C1-6alkylenes group, A represents an oxygen atom, R4represents a substituted phenyl or pyridyl which may have a Deputy, R6represents a hydrogen atom or a C1-6alkyl group, D represents an oxygen atom or sulfur, E is a CH group or a nitrogen atom, or their pharmacologically acceptable salts

The invention relates to the derivatives of hintline formula I in which Z denotes-O-, -NH - or-S-; m = 1-5, integer, provided that when Z represents-NH-, m = 3 - 5; R1is hydrogen, C1-3alkoxy; R2is hydrogen; R3hydroxy, halogen, C1-3alkyl, C1-3-alkoxy, C1-3alkanoyloxy, trifluoromethyl or cyano; X1denotes-O-, -NR7, -NR8CO-, where R7and R8each is hydrogen, C1-3alkyl; R4choose one of the listed in paragraph 1 of the claims of the seven groups, except 4-(3,4,5-trimethoxyphenyl)-6,7-dimethoxyquinazoline, 4-(3-methoxybenzylthio)-6,7-dimethoxyquinazoline, 4-(3-chlorophenylthio)-6,7-dimethoxyquinazoline, 4-(3-chlorophenoxy)-6,7-dimethoxyquinazolin and 4-(3,4,5-trimethoxyaniline)-6,7-dimethoxyquinazolin, or their salts
The invention relates to a method of producing dibenzothiazoledisulphide oxidation alkaline solution of 2-mercaptobenzthiazole oxygen in the presence of a catalyst - derived phthalocyanine cobalt at the 50oWith, the process is carried out at 3-10-fold excess of 2-mercaptobenzthiazole solubility in a weak alkaline medium, where the concentration of the alkali metal hydroxide is 0.35 to 1.0 wt.%, in the presence of desulfosarcina cobalt as a catalyst in number (3-5)X10-4mol 1 mol 2-mercaptobenzthiazole

The invention relates to new pyrimidine derivative of General formula (I) or their pharmaceutically acceptable salts, with high antisecretory activity with the properties of reversible proton pump inhibitor that can be used to obtain valuable medicines
The invention relates to the technology of organic synthesis, namely industrial method for producing N,N'-DICYCLOHEXYL-2-benzothiazolesulfenamide used as accelerator of sulfur vulcanization of rubber mixtures

The invention relates to a method of obtaining modified in the 16,17-position epothilones, according to which the protected position of 3.7 or unprotected epothilone a or b a) hydronaut double bond in position 16,17 or) double bond in position 16,17 spend epoxidation and, if necessary, the obtained epoxide reduced to the alcohol in position 16, to a method for epothilone-N-oxides, in which the protected position of 3.7 or unprotected epothilone And or transferred to N-oxide, the N-oxide optionally subjecting the reaction of Qatar; the method of obtaining modified in the C-19 position epothilones by metallizirovanaya in position C-19 secured or unsecured epothilone a or b, as well as to modified epothilones General formula I

The invention relates to new compounds having formula I or formula II:

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< / BR>
where R1represents H, lower alkylthio or R1together with R2form a-CH2-; each of R2and R3independently represents H or lower alkyl; R4represents Oh or H2; R5is H, unsubstituted lower alkyl, cyclohexyl - lower alkyl; each of R6and R7independently represents hydrogen, phenyl, naphthyl, -C(O)-NHCHR13CO2R14or substituted phenyl, where the Deputy represents halogen, lower alkyl, lower alkoxy, hydroxy, or phenyl - lower alkoxy; R8represents H or lower alkyl; R9represents H or lower alkyl; R12is NR9or S; R13is lower alkylthio; R14represents H or lower alkyl; or their pharmaceutically acceptable salts, with the exception of 4,5-bis(4-methoxyphenyl)-2-(4-thiazolidinediones)thiazole and its hydrochloride

The invention relates to a new derivative of solidilin formula (I) where one of X, Y and Z represents C=O or C=S, and one of the remaining X, Y and Z denotes a group With=, and the other group C=S; R1, R2and R3are Deputy or X, Y and Z, or nitrogen atom and may be the same or different and denote hydrogen, halogen, hydroxy, nitro, etc., the group -(CH2)n-O - and may be joined through the nitrogen atom, or X, Y, Z, n is 1-4, Ar denotes a phenylene or naftilan, R4denotes hydrogen or forms a bond with group a, And denotes nitrogen or CR5, R5denotes hydrogen, halogen or forms a bond with R4In means O or S, when a is CR5and means that, when a is N, its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salt and solvate

The invention relates to the derivatives of propanolamine formula (I) and their pharmaceutically acceptable salts, where R1and R2means phenyl, naphthyl, pyridyl, thienyl, pyrimidyl, thiazolyl, hinely, piperazinil, oxazolyl, which may be substituted with halogen, HE, NO2, NH2, COOH, etc., R3-R8mean hydrogen, hydroxyl, (C1-C8-alkoxy, NH2-THE OTHER9, -N(R9R10, R9-R10mean hydrogen or (C1-C8)alkyl, X is CH or N, Y represents CH or N, provided that the residues R1, R2X and Y are not simultaneously mean R1- phenyl, R2is phenyl, X is CH, Y is CH

The invention relates to a new method of obtaining biphenylenediisocyanate formula (I), its enantiomers and diastereoisomers and its salts, where X is oxygen, Y is nitrogen, each R3and R4directly connected with the carbon ring and independently represents alkyl, each of R1and R2directly connected with the carbon ring and independently represents hydrogen or alkyl, each of R11, R12, R13and R14independently represents hydrogen, J is oxygen, K is nitrogen, L is carbon, R is 0 or an integer from 1 to 2, which includes (a) the interaction of ester of pinacol formula II with haloperidolum compound of formula III in the presence of palladium (0) catalyst and, optionally, the base, with the formation of asutamisega derivative of the formula IV and (b) removing the protection of the nitrogen atom in the compound of formula IV with the formation of the compounds of formula I
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