Pyridine [2,3-d] pyrimidine derivatives as selective kdr and fgfr inhibitors

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of pyridine [2,3-d] pyrimidine of general formula (I) and their pharmaceutically acceptable salts, which possess properties of KDR and FGFR inhibitors. Compounds can be applied to produce medications for treatment of cancer, for instance, of mammary gland, large intestine, lungs and prostate gland. In general formula (I) , Ar and Ar' independently on each other are selected from group that includes phenyl; phenyl substituted with 1-3 substituents selected from group C1-C4alkyl, hydroxy, halogen, halogen-substituted C1-C4alkyl, C1-C4alkoxy; 6-member nitrogen-containing heteroaryl and 6-member nitrogen-containing heteroaryl substituted with C1-C4alkoxygroup, on condition that Ar standing for heteroaryl does not represent 2-pyridyl, and standing for substituted heteroaryl does not represent substituted 2-pyridyl, R1 is selected from group including phenyl, C1-C10alkyl, C1-C10alkyl independently containing substituents selected from group that includes phenyl, C3-C6cycloalkyl. Invention also relates to intermediate compounds for compounds of general formula (I) and to pharmaceutical compositions.

EFFECT: obtaining derivatives and their pharmaceutically acceptable salts which possess properties of selective KDR and FGFR inhibitors.

21 cl, 2 tbl, 20 ex

 

The text descriptions are given in facsimile form.

1. The compounds of formula

or their pharmaceutically acceptable salts, where

Ar and Ar' independently from each other selected from the group comprising phenyl; phenyl substituted by 1-3 substituents selected from group C1-C4alkyl, hydroxy, halogen, halogen-substituted C1-C4alkyl, C1-C4alkoxy; 6-membered nitrogen containing heteroaryl and 6-membered nitrogen containing heteroaryl, substituted C1-C4alkoxygroup is Oh, provided that Ar is heteroaryl does not mean 2-pyridyl and is substituted heteroaryl does not mean substituted 2-pyridyl,

R1selected from the group comprising phenyl,1-C10alkyl, C1-C10alkyl, containing substituents independently selected from the group comprising phenyl,3-C6cycloalkyl.

2. The compounds of formula I according to claim 1, where Ar means a 6-membered nitrogen containing heteroaryl, substituted C1-C4alkoxygroup, non-substituted 2-pyridyl.

3. The compounds of formula I according to claim 2, where Ar denotes a substituted 3-pyridyl.

4. The compounds of formula I according to claim 3, where Ar' is phenyl or phenyl substituted the 1-3 substituents selected from the group comprising From1-C4alkyl, hydroxy, halogen, halogen-substituted C1-C4alkyl, C1-C4alkoxy.

5. The compounds of formula I according to claim 1, where R1means phenyl.

6. The compounds of formula I according to claim 1, where R1means C1-C10alkyl or C1-C10alkyl, containing substituents independently selected from the group comprising phenyl,3-C6cycloalkyl.

7. The compounds of formula I according to claim 1, of formula

or their pharmaceutically acceptable salts, where

R1selected from the group comprising phenyl,1-C10alkyl,

C1-C10alkyl, containing substituents independently selected from the group comprising phenyl,3-C6cycloalkyl,

R2and R3independently selected from the group including halogen, C1-C4alkyl, halogen-substituted C1-C4alkyl, C1-C4alkoxy,

R4, R5, R6, R7and R26independently selected from the group including H, halogen, C1-C4alkyl, halogen-substituted C1-C4alkyl and OR23moreover, at least two of them mean N,

R23means N or C1-C4alkyl.

8. The compounds of formula II according to claim 7, where R6means OR23.

9. The compounds of formula II according to claim 7, where R4and R26mean halogen.

10. The compounds of formula II according to claim 7, where R5and R7mean OR23.

11. The compounds of formula II according to claim 7, where R26means unsubstituted With1-C4alkyl.

12. The compounds of formula II according to claim 7, where R4, R5, R6and R26mean N.

13. The compounds of formula II according to claim 7, where R5and R26mean OR23.

14. The compounds of formula II according to claim 7, where R26means OR23.

15. The compounds of formula II according to claim 7, where R6and R7mean OR23.

16. The compounds of formula II according to claim 7, where R6means OR23.

17. The compounds of formula I, p is 1, selected from the group including

6-(4-methoxyphenyl)-8-phenyl-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

6-(2,6-dichlorophenyl)-8-phenyl-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

6-(3,5-acid)-8-phenyl-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

8-phenyl-2-phenylamino-6-o-tolyl-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

6,8-diphenyl-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

6-(2,5-acid)-8-phenyl-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

6-(2-methoxyphenyl)-8-phenyl-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

6-(3,5-bis-triptoreline)-8-phenyl-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

8-phenyl-2-phenylamino-6-pyridin-4-yl-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

8-phenyl-2-phenylamino-6-pyridin-3-yl-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

6-(3,4-acid)-8-phenyl-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

6-(4-methoxyphenyl)-2-(6-methoxypyridine-3-ylamino)-8-phenyl-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he,

8-isobutyl-6-(4-methoxyphenyl)-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he

8-cyclopropylmethyl-6-(4-methoxyphenyl)-2-phenylamino-5,8-dihydro-6N-pyrido[2,3-d]pyrimidine-7-he.

18. Compounds according to any one of claims 1 to 17, having the properties of a selective inhibitor and the activity of FGFR kinase and KDR to obtain drugs.

19. Pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1 to 18 and a pharmaceutically acceptable carrier or excipient.

20. The pharmaceutical composition according to claim 19, to obtain drugs for cancer treatment.

21. A compound selected from the group comprising methyl ether 3-(2,4-dichloropyrimidine-5-yl)-2-(4-methoxyphenyl)propionic acid, methyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-(4-methoxyphenyl)propionic acid, methyl ester 2-(2,6-dichlorophenyl)-3-(2,4-dichloropyrimidine-5-yl)propionic acid, methyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-(2,6-dichlorophenyl)propionic acid, methyl ester 3-(2,4-dichloropyrimidine-5-yl)-2-(3,5-acid)propionic acid, methyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-(3,5-acid)propionic acid, methyl ester 3-(2,4-dichloropyrimidine-5-yl)-2-o-tolylpropan acid, methyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-o-tolylpropan acid, methyl ester 3-(2,4-dichloropyrimidine-5-yl)-2-phenylpropionic acid, methyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-phenylpropionic acid, ethyl ester 3-(2,4-dichloropyrimidine-5-yl)-2-(2,5-acid)propionic acid, ethyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-(2,5-acid)propionic acid, methyl ester 3-(2,4-dichloropyrimidine-5-is)-2-(2-methoxyphenyl)propionic acid, ethyl ester of 3-(2,4-diphenylbenzidine-5-yl)-2-(2-methoxyphenyl)propionic acid, methyl ester 2-(3,5-bis-triptoreline)-3-(2,4-dichloropyrimidine-5-yl)propionic acid, methyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-(3,5-bis-triptoreline)propionic acid, ethyl ester 3-(2,4-dichloropyrimidine-5-yl)-2-pyridine-4-ylpropionic acid, ethyl ether 3-(2,4-diphenylbenzidine-5-yl)-2-pyridine-4-ylpropionic acid, ethyl ester 3-(2,4-dichloropyrimidine-5-yl)-2-pyridin-3-ylpropionic acid, ethyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-pyridin-3-ylpropionic acid, ethyl ester 3-(2,4-dichloropyrimidine-5-yl)-2-(3,4-acid)propionic acid, ethyl ester 3-(2,4-diphenylbenzidine-5-yl)-2-(3,4-acid)propionic acid, methyl ester 3-(4-chloro-2-phenylaminopyrimidine-5-yl)-2-(4-methoxyphenyl)propionic acid, methyl ester 3-(2-chloro-4-phenylaminopyrimidine-5-yl)-2-(4-methoxyphenyl)propionic acid, methyl ester 3-[2-(6-methoxypyridine-3-ylamino)-4-phenylaminopyrimidine-5-yl]-2-(4-methoxyphenyl)propionic acid, methyl ester 3-(2-phenylamino-4-isobutyleneisoprene-5-yl)-2-(4-methoxyphenyl)propionic acid methyl ester 3-(2-phenylamino-4-cyclopropanemethylamine-5-yl)-2-(4-methoxyphenyl)propionic acid.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: described is obtaining and pharmaceutical application of substituted derivatives of arylalkane acid of formula I , where ring A, ring B, R1, R2, R3, R4, R5, X, Alk1, Alk2, Ar1 and Ar2 are such as determined in said description. Said compounds, as selective agonists activating (RAPPs) receptors, activated by peroximal proliferator, in particular, RXRs/RAPPs-alfa, RXRs/RAPPs-gamma and RXRs/RAPPs-delta heterodimers, are applied in treatment and/or prevention of type 2 diabetes and connected with it metabolic syndrome, such as hypertension, obesity, insulin-resistence, hyperlipidemia, hyperglycemia, hyperolesterinemia, artheriaslerosis, coronary artery disease, and other cardio-vascular disorders, and possess improved profile of side effects, connected with common RAPPs-gamma agonists.

EFFECT: obtaining compunds, which possess improved profile of side effects, connected with common RAPPs-gamma agonists.

22 cl, 38 ex, 2 tbl, 10 dwg

FIELD: chemistry.

SUBSTANCE: novel compounds are selected from group, consisting of: 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl- 4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihudro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4;9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide and 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-benzylamide. Invention also relates to pharmaceutical composition and to application of compounds of general formula 1.

EFFECT: obtaining novel biologically active compounds and based on them pharmaceutical composition, possessing antagonistic activity with respect to vasopressin receptors.

60 cl, 153 ex

FIELD: chemistry.

SUBSTANCE: in general formula I

R1 is phenyl or 5-6-member heterocycle, containing one N atom and/or one O atom; R2 is imidazole or annelated imidazole, selected from group, including a), b), c), d) and e); and R3 stands for hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophen-3-yl, 3-methylbenzo[b] thiophen-2-yl, thiophen-2-yl or thiophen-2-ylmethyl, R4 is hydrogen or lower alkyl, R5 is hydrogen, lower alkyl, halogen, morpholinyl, -NR'R", piperydinyl, optionally substituted with hydroxy-group, or is pyrrolidin-1-yl; R6 is hydrogen or -(CH2)nO-lower alkyl, R7 is hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridin-4-yl, whose ring can contain as substituents lower alkyl, halogen-lower alkyl or pyrrolidin-1-ylmethyl or is -(CH2)n-C(O)-NR'R"; R'/R" independently on each other stand for hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl, X is -CH2-, -NR'''- or -O-; R''' is hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3 or benzyl; n is 1 or 2.

EFFECT: increase of composition and treatment method efficiency.

14 cl, 56 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: in substituted with carbamate groups pyrazolpyridines of general formula (I): R1 stands for group -NR3C(=O)OR4, R2 stands for hydrogen atom or NH2, R3 stands for hydrogen atom or alkyl group with number of carbon atoms from one to four, R4 stands for alkyl group with number of carbon atoms from one to six, as well as to their salt, isomers and hydrates; to methods of their obtaining, medication based on them, as well as to application of said compounds for manufacturing medications for cardio-vascular diseases.

EFFECT: useful biological properties of compounds.

13 cl, 9 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention concerns new histamine receptor blockers in the form of 2,3,4,5-tetrahydro-1H-pyrido-[3,4-b]indoles of the general formula 1 , where: R1 is an aminogroup substitute selected out of optionally substituted C1-C5alkyl; R2i is one or several same or different substitutes selected out of hydrogen, halogen, C1-C3 alkyl, CF3; Ar is phenyl or 5-6-member heterocycle containing 1-2 nitrogen or sulphur atoms in the cycle, unsubstituted or substituted by halogen, C1-C5alkyl, C1-C5alkoxy, substituted aminogroup or trifluormethyl; W is CH2 group optionally substituted CH2CH2 group or optionally substituted CH=CH group.

EFFECT: enhanced antiallergic and autoimmune effect.

4 tbl

FIELD: chemistry.

SUBSTANCE: in novel compounds of formula (I) R1 is selected from , R2 stands for hydrogen or (lower) alkoxy; R3, R4, R5 and R6 are selected each independently from hydrogen, (lower) alkyl, halogenated (lower) alkyl, haloid or cycloalkyl; on condition that R2, R3, R4, R5 and R6 do not all stand for hydrogen; R7, R8 and R9 stand each independently for hydrogen, (lower) alkyl, (lower) alkoxy, (lower) hydroxyalkyl or halogenated (lower) alkyl; on condition that R7, R8 and R9 do not all stand for hydrogen; R10 stands for (lower) alkyl or halogenated (lower) alkyl.

EFFECT: obtaining novel biologically active compounds with improved properties.

16 cl, 38 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new substituted 2,3,4,5-tetrahydro-1N-pyrido[4,3-b]indoles with general formula 1.1, 1.2 or 1.3, their pharmaceutical salts and/or hydrates with antihistamine activity. In general formulae 1.1, 1.2 or 1.3 radicals assume values given below . In 1.1 compounds, R1 represents a substitute, chosen from hydrogen or unsubstituted C1-C5 alkyl; R2 represents a hydrogen atom or C1-C4 alkyl; R3i represents one or more single or different substitutes, chosen from hydrogen, halogen, C1-C3 alkyl or CF3; n=0 or 1-3; in 1.2 compounds R1 represents a substitute of an amino group, chosen from hydrogen or optionally substituted C1-C5 alkyl; R3 represents one or more single or different substitutes, chosen from hydrogen, halogen, C1-C3 alkyl or CF3, and Ar1 represents an aryl or heterocyclyl, containing at least one carboxyl and/or alkoxycarboxyl substitute or R3i represents a carboxyl and/or alkyloxycarboxyl substitute, and Ar1 represents optionally substituted aryl or heterocyclyl; in 1.3 compounds, R2 represents a hydrogen atom or C1-C4 alkyl; R3i represents one or more single or different substitutes, chosen from hydrogen, halogen, C1-C3 alkyl or CF3, and Ar2 represents optionally substituted aryl or heterocyclyl; k=0 or 1-4; m=1 or 2.

EFFECT: compounds can be used for making drug formulation for treating allergies, autoimmune diseases such as pollen allergy, urticaria, bronchial asthma etc.

17 cl, 10 dwg, 2 tbl,13 ex

FIELD: chemistry.

SUBSTANCE: invention refers to of serotonin receptor 5-NT6 antagonists, simultaneously regulating calcium ions homeostasis in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of general formula I, its pharmaceutically acceptable salt and/or hydrate. In general formula I where: R1 is amides substitute selected from optionally substituted C1-C5 alkyl; R2i represents one or number of identical or various substitutes selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar represents halogen unsubstituted or substituted C1-C6 alkyl, C1-C6 alkoxy, phenyl substituted with amides or trifluoromethyl or optionally substituted aromatic hexamerous heterocycle containing 1-2 nitrogen atoms per one cycle, W represents ethyl group-CH2CH2 - vinyl group or ethynyl group. Invention also concerns new compounds selected from group of compounds of formula 1, methods of production thereof, pharmaceutical compositions and methods of their use.

EFFECT: production of composition that simultaneously regulates calcium ions homeostasis in cells.

34 cl, 7 dwg, 4 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: present invention concerns new piperidinyl compounds of the formula (I) and (II) which are selectively binding integrine receptors, pharmaceutical compositions and application of the compositions for obtaining medication with antagonistic effect on integrine receptors, where W, R2, Z and q are described in the claim.

EFFECT: pharmaceutical composition for obtaining medication with antagonistic effect on integrine receptors.

33 cl, 1 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the general formula: , where R1 is an inferior alkyl, -(CH2)n-aryl, unsubstituted or substituted by one or two substitutes from the group of inferior alkyl, inferior alkoxy-, halogen or trifluormethyl, or pyridine; R2 is an inferior alkyl, -(CH2)n- aryl, unsubstituted or substituted by one or two substitutes from the group of inferior alkyl, inferior alkoxy-, halogen or trifluoromethyl, nitro-, cyano-, -NR'R", hydroxy-, or heteroaryl group that is a monovalent heterocyclic 5- or 6-membered aromatic radical with N atoms, either R2 is a heteroaryl that is monovalent heterocyclic 5- or 6-membered aromatic radical where heteroatoms are chosen from N, O or S group, unsubstituted or substituted by one or two substitutes from the group of inferior alkyl or halogen; R3 is pyridine or aryl, unsubstituted or substituted by a halogen or inferior alkyl; R4 is hydrogen or hydroxy-. A is -S(O)2- or -C(O)-; X, Y are -CH2- or -O- independently from each other, though both X and Y should not be -O- at the same time; R'R" are hydrogen or inferior alkyl independently from each other; n is 0, 1 or 2. Also the invention concerns pharmaceutically acceptable additive salts and acids of the compounds, and a medicine based on it.

EFFECT: new biologically active compounds show inhibition effect in glycine absorption.

21 cl, 214 ex, 1 tbl

The invention relates to new derivatives of 4-hydroxypiperidine General formula (I), where X denotes-O-, -NH-, -CH2-, -CH= , -CO2-, -SOP(lower alkyl) -, or-CONH-, R1- R4independently from each other, is hydrogen, hydroxy, nitro-group, a lower alkylsulfonyl, 1 - or 2-imidazolyl, 1-(1,2,4-triazolyl), R5and R6independently from each other, is hydrogen, lower alkyl, hydroxy - or oxoprop, R7- R10independently from each other, is hydrogen, lower alkyl, halogen, trifluoromethyl or lower alkoxygroup, n = 0 or 1, or their pharmaceutically acceptable acid additive salts

The invention relates to new cycloalkenes and cycloalkanes, suitable as pharmaceutically active substances, more particularly to derivatives of 1,3-substituted of cycloalkene and cycloalkane formula (I)

Z-CH2-Y (I)

where Z stands for a group

< / BR>
where

where R is aryl, 2-, 3 - or 4-pyridinyl, unsubstituted or substituted lower alkyl, lower alkoxyl, hydroxyl or halogen, 2-, 4 - or 5-pyrimidinyl, unsubstituted or substituted lower alkyl, lower alkoxide, hydroxyl or halogen, 2-pyrazinyl, unsubstituted or substituted lower alkyl, lower alkoxyl, hydroxyl or halogen, 2 - or 3-thienyl, unsubstituted go substituted lower alkyl or halogen, 2 - or 3-furanyl, unsubstituted or substituted lower alkyl or halogen, 2-, 4 - and 5-thiazolyl, unsubstituted or substituted lower alkyl or halogen, 3-indolyl, 2-, 3 - or 4-chinoline, and m is the number 1, 2, or 3, or group

< / BR>
in which R and m have the above meanings;

Y - group

< / BR>
where R is the specified value,

mixtures of their isomers or the individual is

The invention relates to new biologically active compounds, in particular to new pyridone derivative exhibiting analgesic activity

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 general formula , R is unsubstituted or substituted with -OH, C1-4alkyl or -O-C1-4alkyl, straight or branched alkyl C1-C4; R1 has formula -(L)x-R3; R3 is a fragment, chosen from a group consisting of substituted or unsubstituted phenyls, where the substitute is chosen from C1-4alkyl, -O-C1-4alkyl, -S-C1-4alkyl or fluorine; R2 has formula -(L1)y-R4; R4 is a fragment, chosen from a group consisting of i) hydrogen atom; ii) substituted with -OH, -O-C1-4alkyl or phenyl or unsubstituted straight or branched hydrocarbyls C1-C10, where the hydrocarbyl is C1-6alkyl; L and L1 are bridge fragments -NR5-; each of the fragments R5 is a hydrogen atom, straight or branched alkyl C1-C4; indices x and y can independently assume values 0 and 1.

EFFECT: compounds can be used for curing diseases, mediated by activity of phlogistic cytokines, such as arthritis.

10 cl, 4 dwg, 3 tbl, 200 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new pyrimidine of the general formula (I), which possess properties of the inhibitor of CDK-kinase. In the general formula (I) R1 designates hydrogen, halogen, C1-C6alkyl, R2 designates C1-C10alkyl, C1-C10alkenyl, or C3-C10cycloalkyl which can be mono-, bi- or tricyclic or denotes one- or polysubstituted by identical or different substitutes from the number of hydroxy-group, halogen, C1-C6alkoxygroup, C1-C6kalkylthiogroup, -NH-(CH2)n-C3-C10cycloalkyl, C3-C10 cycloalkyl, C1-C6hydroxyalkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, -NHC1-C6alkyl, -N(C1-C6alkyl)2, C1-C6alkanoil, -CONR3R4, -COR5, C1-C6alkylOAc, where Ac indicates C1-C4alkylCO-group, carboxygroups, phenyl, 5-6-member heteroaryl, containing 1-2-heteroatom in the ring, selected from nitrogen, -(CH2)n- phenyl, -(CH2)n-5-6-member heteroaryl containing 1-2-heteroatom in a ring, selected from nitrogen, phenyl-(CH2)n-R5, -(CH2)nPO3(R5)2 and -R6 and -NR3R4C1-C10alkyl, or C3-C10cycloalkyl, in this case phenyl, C3-C10 cycloalkyl, heteroaryl, -(CH2)n-phenyl and -(CH2)n heteroaryl can be one or polysubstituted by identical or different substitutes from halogens, hydroxygroup, C1-C6alkyl, C1-C6alkoxygroup, benzoxy-group and -CF3 groups, and ring of C3-C10 cycloalkyl and C1-C10alkyl can be separated by one or several nitrogen atoms, oxygen and/or sulfur and/or the said ring can be interrupted by one or two groups of =C=O or R2 designates the group X designates oxygen or group-NH-, and one of A and B independently indicates hydrogen, and the other indicates hydrogen, hydroxygroup, C1-C3alkyl, C1-C6alkyoxy,group SR7, SO2R7, CO(OH)R7, CR7(OH)R7, C1-C6alkyl-P(O)OR3OR4, COR7 or A and B together form C3-6-cycloalkyl ring which does not necessarily have to be interrupted by 1-3 atoms of nitrogen, oxygen and/or sulfur and/or can be interrupted by =C=O or =SO2 groups, and/or does not necessarily have to contain one or several double bonds, X designates oxygen or group-NH-, either one from A and B independently indicates hydrogen, and the other indicates hydrogen, hydroxygroup, C1-C3alkyl, C1-C6alkyoxy,group SR7, SO2R7, CO(OH)R7, CR7(OH)R7, C1-C6alkyl-P(O)OR3OR4, COR7 or A and B together form C3-6-cycloalkyl ring which does not necessarily have to be interrupted by 1-3 atoms of nitrogen, oxygen and/or sulfur and/or can be interrupted by =C=O or =SO2 groups, and/or does not necessarily have to contain one or several double bonds, values of R3 -R10 are specified in the formula of the invention.

EFFECT: connections can be used for the treatment of cancer, autoimmune diseases caused by chemotherapeutic means of alopecia and inflammations of mucous membrane, cardiovascular diseases, infectious diseases, chronic neurodegenerative and viral infections.

13 cl, 1 tbl, 540 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention relates to the pyrimidine derivatives with general formula I and their pharmaceutically acceptable salts, which possess tyrosine kinase ZAP-70, FAK and Syk-inhibiting activity, and to their application. The compounds can be used for treatment or prevention of diseases or conditions, where the activation of tyrosine kinase ZAP-70, FAK and/or Syk is involved, e.g., heart failure, chronic obstructive pulmonary disease, Alzheimer's disease et al. In general formula (I) , X is for CR0; R0, R1, R2, R3 and R4 - each identifies independently hydrogen; C1-C8alkyl; hydroxyC1-C8 alkyl; or R3 and R4 together with the adjoined nitrogen and carbon atoms create the 5-10-term heterocyclic ring and, besides, contain 1, 2 or 3 heteroatoms, chosen from N, O and S; or R1 , R2 and R3 each identifies independently the halogen; C1-C8alcoxy; hydroxyC1-C8 alcoxy; C1-C8 alcoxy -C1-C8 alcoxy; phenyl; 5-6-term heterocyclic ring; containing 1-4 heteroatoms, chosen from N and O; nitro; carboxy; -N(C1-C8alkyl)C(O)-C1-C8 alkyl; -CONR10R11; -SO2N(R10)R11; where R10 and R11 each identifies independently the hydrogen; hydroxy; C1-C8 alkyl; C2-C8alkenyl; C3-C8cycloalkyl; C3-C8 cycloalkyl -C1-C8 alkyl; C2-C8 alcoxy -C1-C8 alkyl; hydroxy C1-C8 alcoxy -C1-C8 alkyl; hydroxyC1-C8 alkyl; or 5-10-term heterocyclic ring, containing up to two heteroatoms, chosen from N and S; or R1 and R2 together with the adjoined carbon atoms create the aryl or 5-10-term heteroaryl radical, containing one or two heteroatoms, chosen from N, O and S; or R5 and R6 identifies independently from each other the hydrogen; halogen; cyano; C1-C8 alkyl; haloC1-C8alkyl; R7, R8 and R9 identifies independently from each other the hydrogen; hydroxy; C1-C8alkyl; haloC1-C8alkyl; C1-C8alcoxy; -Y-R12, where Y means the simple link or O and R12 means C1-C4alkyl, substituted or unsubstituted 5-, 6- or 7-term heterocyclic ring, containing 1, 2 or 3 heteroatoms, chosen from N, O and S; carboxy; -N(C1-C8 alkyl)-CO-NR10R11; - -N(R10)(R11); R7 and R8 or R8 and R9, correspondingly, together with the adjoined carbon atoms create the 5- or 6-term heteroaryl containing 1, 2 or 3 heteroatoms, chosen from N; or 5- or 6- term carbocyclic ring; or R7 means hydrogen, hydroxyl, C1-C4alkyl, unsubstituted or terminally substituted hydroxyl group; C1-C8alcoxy group, unsubstituted or terminally substituted by hydroxyl, C1-C4 alcoxy group or unsubstituted or substituted C1-C4alkyl 5-6-term heterocyclic ring, containing 1-3 heteroatoms, chosen from N and O; Provided, one R1, R2 or R3 means -CON(R10)R11; or -SO2N(R10)R11.

EFFECT: therapeutic efficiency is increased.

7 cl, 14 tbl, 184 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes novel derivatives of triazolo[4,5-d]pyrimidine of the general formula (I): wherein R1 means (C3-C5)-alkyl that can be substituted with halogen atom; R2 means phenyl that can be substituted with fluorine atom; R3 and R4 are similar and mean hydroxy-group; R means XOH wherein X means -CH2, -OCH2CH2 or a bond, or their pharmaceutically acceptable salt or solvate of solvate of such salt under condition that when X means -CH2 or a bond then R1 doesn't mean propyl group; when X means -CH2 and R1 means -CH2CHCF3, butyl or pentyl groups then phenyl group at R2 must be substituted with fluorine atom; when X means -OCH2CH2 and R1 means propyl then phenyl group at R2 must be substituted with fluorine atom. Also, invention describes a pharmaceutical composition based on these compounds, method for their synthesis and novel intermediate compounds of the formula (II) , (V) and R-(R*,R*)-2,3-dihydroxybutanedioate (1:1) of compound of the formula (III): . Also, invention relates to a method for treatment of diseases mediated by P2T-receptors, such as myocardium infarction, prophylaxis or propagation of tumors and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions, improved method of synthesis.

15 cl, 9 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) or their pharmaceutically acceptable salts or solvates possessing properties of modulator of activity of insulin-like growth factor-1 (IGF-1) receptors, their synthesis and using. These compounds can be used in cancer treatment also. In the general formula (I) R1 represents a 5- or 6-membered heteroaromatic ring comprising at least one ring heteroatom chosen from nitrogen, oxygen or sulfur atom and wherein this ring is optionally substituted with at least a substitute chosen from (C1-C6)-alkyl, (C1-C6)-alkoxy-group (each can be optionally substituted with at least one substitute chosen from halogen atom, hydroxyl and trifluoromethyl group), halogen atom, cyano-group, hydroxyl, (C1-C6)-alkoxycarbonyl, -C(O)NR7N8, and unsaturated 5-6-membered ring that can comprise at least one heteroatom chosen from nitrogen atom, and wherein this ring is optionally substituted with at least one substitute chosen from (C1-C6)-alkyl, (C1-C6)-alkoxy-group (each can be optionally substituted with at least one substitute chosen from halogen atom, hydroxyl and trifluoromethyl group), halogen atom and cyano-group; R2 represents (C1-C4)-alkyl group; R3 represents hydrogen atom or halogen atom; R4 represents 5-membered heteroaromatic ring comprising at least one ring heteroatom chosen from nitrogen atom, and wherein this ring is optionally substituted with at least one substitute chosen from (C1-C6)-alkyl, (C1-C6)-alkoxy-group (each can be optionally substituted with at least one substitute chosen from halogen atom, hydroxyl and trifluoromethyl group),(C3-C6)-cycloalkyl; each R7 and R8 represents independently hydrogen atom, or R7 and R8 in common with nitrogen atom to which they are bound form 4-6-membered saturated heterocycle.

EFFECT: improved method of synthesis and preparing, valuable medicinal properties of compounds and pharmaceutical composition.

24 cl, 102 ex

FIELD: organic chemistry, chemical technology, fungicides.

SUBSTANCE: invention relates to a novel compound - 4-methoxy-5-nitro-6-thiocyanopyrimidine of the formula (I) that possesses fungicide activity in experiments in separate strains of fungi (in vitro) and in field conditions (in vivo). Also, invention relates to a method for synthesis of 4-methoxy-5-nitro-6-thiocyanopyrimidine. Method involves interaction of 4-methoxy-5-nitro-6-chloropyrimidine with alkaline metals or ammonium thiocyanate. As usually, the process is carried out at temperature 20-500C in organic solvent medium.

EFFECT: improved method of synthesis.

3 cl, 1 sch, 6 tbl, 4 ex

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