Pyrazole derivatives and use thereof as receptor tyrosine kinase inhibitors

FIELD: chemistry.

SUBSTANCE: present invention relates to novel pyrazole derivatives of formula (I) or pharmaceutically acceptable salts thereof, having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths accompanied by high level of Trk, to a method of producing said derivatives, use thereof to prepare a medicinal agent, pharmaceutical compositions based on said derivatives, a method of inhibiting Trk activity and a method of obtaining antiproliferative action. where A denotes a single bond or C1-2alkylene; where the said C1-2alkylene can be optionally substituted with one R22; ring C is a phenyl or a 5-6-member heterocyclic ring with 1-2 heteroatoms selected from N or S. Values of R1-R7, R22 and n are given in the formula of invention.

EFFECT: obtaining pharmaceutically acceptable salts having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths.

20 cl, 5 dwg, 193 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):

in which a represents a simple bond or a C1-2alkylen; where specified With1-2alkylene optionally may be substituted with one R22;
the ring is a phenyl or 5-6-membered heterocyclyl with 1-2 heteroatoms, selected from N or S;
R1and R4independently selected from hydrogen, C1-6of alkyl, C1-6alkoxy, C1-6S(O)andwhere a is 0, C3-6cycloalkyl; where R1and R4independently of each other optionally may be substituted at carbon atoms by one or more R8;
R2selected from hydroxy, amino, C1-6of alkyl, C1-6alkoxy, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl or 5-6-membered heterocyclyl with 1-2 heteroatoms, selected from N, O or S; where R2optionally may be substituted at a carbon atom by one to three R10;
R3selected from halogen, nitro, cyano, C1-6of alkyl, C1-6alkoxy;
R5represents hydrogen or C1-6alkyl;
R6and R7independently selected from hydrogen, halogen, nitro, amino, C1-6of alkyl, N-(C1-6alkyl)amino, C1-6is alkoxycarbonyl; where R6and R7independently of each other optionally may be substituted at a carbon atom by one to three R15;
or R6and R7together with the pyrimidine bond to which they are attached, form a 5 - or 6-membered carbocyclic ring or a 5 - or 6-membered heterocyclic ring with 1 or 2 heteroatoms selected from N or S, where the specified carbocyclic ring or heterocyclic ring optionally may be substituted at a carbon atom with one R17;
n=0 or 1;
R10, R15, R17and R22independently selected from halogen, hydroxy, amino, carboxy, C1-6of alkyl, C1-6alkoxy; where R17may be optionally substituted at a carbon atom with one R19;
R19choose from C1-6alkoxy or 5-6-membered heterocyclyl with 1-2 heteroatoms, selected from N or O; where R19optionally may be substituted at a carbon atom with one R23;
R23represents methyl;
or its pharmaceutically acceptable salt;
provided that the compound is not:
5-bromo-N4-(5-methyl-1H-pyrazole-3-yl)-N2-[1-(2-pyridinyl)propyl]-2,4-pyrimidinediamine;
5-chloro-N4-(5-methyl-1H-pyrazole-3-yl)-N2-[1-(2-pyridinyl)propyl]-2,4-pyrimidinediamine;
5-bromo-N2-[1-(3-methyl-5-isoxazolyl)ethyl]-N4-(5-methyl-1H-pyrazole-3-yl)-2,4-pyrimido the diamine;
5-chloro-N2-[1-(3-methyl-5-isoxazolyl)ethyl]-N4-(5-methyl-1H-pyrazole-3-yl)-2,4-pyrimidinediamine;
5-bromo-N4-(5-methyl-1H-pyrazole-3-yl)-N2-[1-(3-pyridinyl)propyl]-2,4-pyrimidinediamine;
5-chloro-N4-(5-methyl-1H-pyrazole-3-yl)-N2-[1-(3-pyridinyl)propyl]-2,4-pyrimidinediamine;
5-chloro-N4-(5-methyl-1H-pyrazole-3-yl)-N2-[1-(3-pyridinyl)ethyl]-2,4-pyrimidinediamine;
5-bromo-N4-(5-methyl-1H-pyrazole-3-yl)-N2-[1-(3-pyridinyl)ethyl]-2,4-pyrimidinediamine; or
5-bromo-N4-(5-methyl-1H-pyrazole-3-yl)-N2-[1-(2-pyridinyl)ethyl]-2,4-pyrimidinediamine.

2. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where a represents a simple bond.

3. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R4represents hydrogen.

4. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R2selected from C1-6the alkyl.

5. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R3represents fluorine.

6. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R5represents hydrogen.

7. The method of obtaining the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6, including the interaction of a pyrimidine of formula (IV):

where L pre who is a displaced group;
with the compound of the formula (V):

and then, if necessary:
i) the conversion of compounds of formula (I) into another compound of formula (I);
ii) removing any protective groups;
iii) formation of pharmaceutically acceptable salts.

8. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 for use as a medicine with any abscopal properties tyrosine kinase Trk.

9. The use of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6 for preparing a medicinal product for use for the inhibition of Trk activity.

10. The use of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6 for preparing a medicinal product for use for the treatment or prevention of malignant tumors, accompanied by increased levels Trk.

11. The use of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6 for the preparation of drugs with antiproliferative action.

12. The method of inhibition of Trk activity involving the introduction of a therapeutically effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6.

13. The method of obtaining antiproliferative the steps, which provides for the introduction of an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6.

14. Pharmaceutical composition comprising an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6 with at least one pharmaceutically acceptable carrier, diluent or excipient, for use in inhibiting the activity of the Trk.

15. Pharmaceutical composition comprising an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6 with at least one pharmaceutically acceptable carrier, diluent or excipient, for use for the treatment or prevention of malignant tumors, accompanied by increased levels Trk.

16. Pharmaceutical composition comprising an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6 with at least one pharmaceutically acceptable carrier, diluent or excipient, to obtain antiproliferative action.

17. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 for use for the inhibition of Trk activity.

18. The compound of formula (I) or its pharmaceutically acceptable salt p the claim 1 for use for the treatment or prevention of malignant neoplasms, accompanied by increased levels Trk.

19. The compound of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 6 for antiproliferative action.

20. The use of claim 10, where the specified cancer selected from ovarian cancer, breast cancer, colorectal cancer and prostate cancer.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to use of tetrahydrobenzo[4,5]thiophene[2,3-d]pyrimidine derivatives, including groups of known compounds, having formula (I), for preparing a medicinal agent for treating and/or preventing diseases and disorders which require inhibition of the 17β-hydroxysteroid-dehydrogenase (17β-HSD) enzyme, more preferably which require inhbition of type 1 17β-HSD enzyme, type 2 17β-HSD enzyme or type 3 17β-HSD enzyme. In formula X denotes S or SO2, R1 and R2 are separately selected from a group which includes -C1-C12alkyl, where the alkyl can be straight, cyclic, branched or partially unsaturated, and can be optionally substituted with up to three substitutes, independently selected from a group consisting of hydroxyl, C1-C12alkoxy group, thiol, C1-C12alkylthio-, aryloxy group, -CO-aryl, -CO-OR, -O-COR, -O-CO-heteroaryl and a -N(R)2 group; where the said aryl group is phenyl or naphthyl and can be optionally substituted with up to 3 halogen atoms; where the said heteroaryl group is thienyl, furyl or pyridyl; -aryl and arylC1-C12alkyl, where the aryl is selected from a group consisting of phenyl, biphenyl, naphthyl, indanyl, indenyl and fluorenyl. Other values of substitutes are given in the formula of invention.

EFFECT: high efficiency of using novel compounds in therapy.

32 cl, 3 tbl, 7 dwg, 151 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel compounds of formula where values of radicals are given in the formula of invention, and a pharmaceutically acceptable salt thereof. Said compounds have 17β-hydroxysteroid dehydrogenase enzyme (17β-HSD) inhibiting activity. The invention describes use of the formula (I) compound in treating or preventing diseases or disorders which require inhibition of 17β- hydroxysteroid dehydrogenase enzyme, use of the formula (I) compound to prepare a medicinal agent for treating or preventing diseases or disorders which require inhibition of 17β- hydroxysteroid dehydrogenase enzyme, and a pharmaceutical composition based on the formula (I) compound.

EFFECT: derivatives are highly effective.

18 cl, 7 tbl

FIELD: chemistry.

SUBSTANCE: use of compounds of formula (I): where: X denotes >CR1R2 or, when R6 denotes H, X denotes >SO2; Y denotes >CR1R2; Z denotes >C=O, >CH2, single bond; R1 denotes H, R2 denotes H, -COOH, -OH; or R1 and R2 together denote =O, ethylenedioxy or hydroxyimino group; R3 denotes H, lower alkyl group; R4 denotes two H, =O, hydroxyimino group; R5 denotes H, lower alkyl group, halogen; R6 denotes H, lower alkoxy, COOH; R7 and R8 are identical or different from each other and each denotes H, lower alkyl, halogen; and pharmaceutically acceptable salts thereof and esters for preparing a medicinal agent.

EFFECT: agent having neuroprotective action against hypoxia.

2 tbl, 24 ex, 13 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) and formula (II), their tautomers and pharmaceutically acceptable salts. In formula (I) and in formula (II), X - S; R1 - H; R2 - NR5R6; R3 - 5-6-member heteroaryl with 1 heteroatom, selected from N and S, or phenyl, optionally substituted with one or two substituents, selected from halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenalkyl and C1-C6-halogenalkoxy; R4 - H, C1-C6 alkyl, C1-C6 alkoxy or XR3, where X and R3 are determined above; R5 - H; R6 - H; L - N or CR7, where R7 - H; M - S. Invention also relates to pharmaceutical composition, containing as active component invention compound, to method of inhibiting activity of caseinkinase lε and to method of obtaining compounds of formula (I) or formula (II).

EFFECT: compounds of claimed invention possess properties of casein kinase lε inhibitors.

13 cl, 5 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention describes a neutral semiconductor organic compound of formula (I) , where R1 and R2 denote a hydrogen atom, n is the number links in formula (I) and is an integer between 2 and 1000, terminal groups of the compound R3 and R4 denote a hydrogen atom or a linear or branched alkyl group with 1-20 carbon atoms. The invention also describes use of the said compound as a semiconductor in electronic functional elements.

EFFECT: higher oxidation resistance, which enables use of the compound in transistors and other electronic functional elements.

5 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula I. In general formula I A is C or N; B, D and E independently represent CR4, NR5, N, O or S; and a ring containing groups A, B, D, E, selected from thienyl, furan, imidazole, oxazole, isothiazole, thiazole, pyrrol, pyrazole; provided that: b) when A is N, not any of B, D, E can be O or S; and c) when A is C, B is CR4 and one of D or E is N or NR5, when any of D or E cannot be NR5 or N; G is N or C; R1 represents one or more substitutes selected from H, Ra halogen, -OH and -ORa; R2 represents one or more substitutes selected from H, halogen and C1-6-alkyl, and also one of substitutes R2 can be -ORb' , -NRb' Rb', -SRb', -SORb', -SO2Rb', -SO2NRb' Rb'; R3 is H, or Cy, selected from phenyl optionally substituted with one or more substitutes selected from Rc , where Rc independently represents halogen, -ORg', where Rg' independently represents a Rg group, where Rg is C1-6-alkyl; each R4 independently represents H, Re, halogen, -CORe', -CO2Re', -CONRe'Re', -NRe'Re'; R5 independently represents H, Re, -CORe, -CONReRe, -SORe or -SO2Re; each Ra independently represents C1-6-alkyl or halogen- C1-6-alkyl; each R independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rb' independently represents H or Rb; each Rc independently represents halogen, -ORg', -CONRg'Rg', -NRg'Rg'; Rd is Cy optionally substituted with one or more Rf substitutes; each Rc independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rc and Cy*, or Re is Cy, where any of the groups Cy or Cy* can optionally be substituted with one or more substitutes selected from Rc and Rg ; each Re' independently represents H or Re; each Rf independently represents a halogen, -ORh', -CO2Rh; each Rg independently represents Rd or C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rg' independently represents H or Rg; each Rh independently represents C1-6-alkyl, halogen-C1-6-alkyl or hydroxy- C1-6-alkyl; each Rh' independently represents H or Rh; and Cy or Cy* given in definitions above is a partially saturated, saturated or aromatic 3-7-member monocyclic carbocyclic ring which optionally contains 1-2 heteroatoms selected from N and O, and where the ring or rings can be bonded to the remaining part of the molecule through a carbon or nitrogen atom.

EFFECT: obtaining formula I compounds with p38-kinase inhibitory properties which can be used in making drugs for treating such diseases as tumour immune and autoimmune diseases etc.

21 cl, 10 dwg, 8 tbl, 57 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I , where R1 is C1-C7-alkyl; R2 is C1-C7-alkyl, C1-C7-haloalkyl, C3-C8-cycloalkyl; R3 is -NRaRb; possibly substituted phenyl, thiophenyl, furanyl, where the substitutes are selected from a group consisting of halogen, C1-C7-alkoxy, C1-C7-alkylsulphonyl and -C(O)O-C1-C7-alkyl; R4 is hydrogen or C1-C7-alkyl; R5 is hydrogen, halogen, C1-C7-alkyl, phenyl; or R5 together with R4 can form a ring selected from a group consisting of C5-C7-cycloalkyl, tetrahydrofuranyl, piperidine, tetrahydropyran, phenyl or pyridinyl, which can possibly be substituted with -C(O)O-C1-C7-alkyl; Ra and Rb together with the nitrogen atom to which they are bonded form piperidine; and to pharmaceutically acceptable salts thereof. The invention also relates to a medicinal agent based on the said compounds which has GABA-B receptor allosteric enhancement effect.

EFFECT: obtaining novel compounds and a medicinal agent based on the said compounds, which can be used in medicine for treating central nervous system disorders.

13 cl, 42 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel 1-thio-D-glucitol compounds of formula I or to pharmaceutically acceptable salts thereof or hydrates of the compound or salts: , [where R1, R2, R3 and R4 are identical or different, and each is a hydrogen atom, C1-C6-alkyl group), A is -(CH2)n-, -CONH(CH2)n-, -O- or -(CH2)nCH=CH- (where n is an integer from 0 to 3, Ar1 is an arylene group, heteroarylene group, which is an unsaturated 5-9-member mono- or bicyclic group, containing 1-2 heteroatoms, selected from S and N, Ar2 is an aryl group or heteroaryl group which is an unsaturated 5-9-member mono- or bicyclic group containing 1-2 heteroatoms selected from O, S and N, and R5, R6, R7, R8, R9 and R10 are identical or different, and each is (i) a hydrogen atom, (ii) a halogen atom, (iii) a hydroxyl group, (iv) C1-8-alkyl group, optionally substituted with hydroxyl group(s), (v) -(CH2)m-Q {where m is an integer from 0 to 4, and Q is -CO2H, -ORc1, -CO2Ra3, -SRe1, -NHRa6 or -NRa7Ra7 (where each of Ra3, Ra6 and Ra7 is a C1-6-alkyl group, Rc1 is a C1-6-alkyl group, and Rc1 is a C1-6-alkyl group)}, (vi) -O-(CH2)m'-Q' {where m' is an integer from 1 to 4, and Q' is a hydroxyl group,-CO2H, -CO2Ra8, -CONRa10Ra10, -NRa12Ra12 (where each of Ra8, Ra10 and Ra12 is a C1-6-alkyl group)}, (vii) -ORf {where Rf is C3-7-cycloalkyl group or tetrahydropyranyl group)}, (viii) morpholine group, (ix) phenyl group, (x) pyridyl group]. The invention also relates to 1-thio-D-glucitol compounds of formulae IA, II, III, IV, to a pharmaceutical agent, to methods of obtaining 1-thio-D-glucitol compounds, as well as to compounds of formulae XIII, XIV.

EFFECT: obtaining novel biologically active compounds which are inhibitors of sodium-dependent co-transporter-2-glucose.

25 cl, 140 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel acetylenyl-pyrazole-pyrimidine derivatives of general formula (I), having mGluR2 (metabotropic glutamate receptor) antogonist properties). In compounds of general formula (I): either E and J denote N, G denotes C and L denotes N, M denotes CH, or M denotes N, L denotes CH; or L and G denote N, E denotes C, and J and M denote CH; or J, G and L denote N, E denotes C, and M denotes CH; or E and L denote N, J and M denote CH, and G denotes C; R1 denotes H, halogen, CF3, CHF2 or C1-6alkyl; R2 denotes H, halogen, C1-6-alkyl, C1-6-alkoxy, CF3 or CHF2, wherein R1=R2≠H; R3 denotes H; -C(CH3)2OH; linear C1-4-alkyl or C3-4-cycloalkyl, which are possibly substituted with one or more substitutes selected from a group comprising 1-3 F and 1-2 OH; A is selected from a group comprising phenyl or a 5- or 6-member heteroaryl having in the ring 1-2 heteroatoms selected from nitrogen, sulphur or nitrogen and sulphur in the 5-member ring, and 1-2 nitrogen atoms i the 6-member ring, and possibly substituted with 1-3 Ra; Ra denotes halogen; hydroxy; cyano; CF3; NReRf; C1-C6-alkyl, possibly substituted amino or hydroxy; ; C1-6-alkoxy; C3-4-cycloalkyl; CO-NRbRc, SO2-NRbRc; or SO2-Rd-; Rb and RC can be identical or different and are selected from a group comprising H; normal or branched C1-6-alkyl, possibly substituted with one or more substitutes selected from a group comprising F, cyano, hydroxy, C1-6-alkoxy, -NH-C(O)-O-C1-6-alkyl, amino, (C1-6-alkyl)amino, di(C1-6-alkyl)amino, heterocycloalkyl having 6 ring atoms, from which 1-2 heteroatoms are selected from nitrogen or nitrogen and oxygen, or a 6-member heteroaryl with one nitrogen heteroatom in the ring; or a 6-membeer heteroaryl with one nitrogen heteroatom in the ring; or Rb and Rc, together with the nitrogen atom with which they are bonded, can form a heterocyclic ring having 6 members in the ring, from which 1-2 atoms are selected from nitrogen and/or oxygen, and which can be substituted with C1-6-alkyl; Rd denotes OH or C1-6-alkyl; Re and Rf denote H, C1-6-alkyl, possibly substituted hydroxy, -C(O)- C1-6-alkyl; S(O)2-C1-6-alkyl.

EFFECT: compounds can be used in preparing medicinal agents for treating central nervous system (CNS) disorders, such as Huntington's chorea, amyotrophic lateral sclerosis, dementia caused by AIDS, parkinsonism etc.

55 cl, 6 dwg, 321 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the 2,9-disubstituted imidazo[1,2-a]benzimidazole family, specifically to water-soluble salts of 9-aminoethyl-substituted 2-(4-fluorophenyl)imidazo[1,2-a]benzimidazole of general formula I:

,

where NR2 = pyrrolidine-, piperidine-, morpholine-; Y=HBr, H2SO4, (CH2COOH)2 and [CH(OH)COOH]2; n=1, 2.

EFFECT: novel compounds have analgesic action.

2 cl, 2 tbl, 15 ex

Pyrazolepyrimidines // 2412186

FIELD: chemistry.

SUBSTANCE: compounds can be used to treat tumourous diseases, such as solid tumours, breast, lung, large intestine or prostate gland tumours. In compounds of formula

: R1 is selected from a group comprising: (a) saturated cyclic radical containing 3-8 ring atoms, from which 1-3 atoms are N atoms, which can contain up to four substitutes independently selected from a group comprising: (i) lower alkyl; and (ii) CO2R3, OR7 or S(O)nR8; (b) C6-C10aryl, which can contain up to four substitutes independently selected from a group comprising: (i) S(O)nR8, lower alkyl; OR7 and halogen; (c) C3-C8cycloalkyl, which can be substituted with NR5R6; and (d) lower alkyl, which can be substituted: (i) OR7, NR5R6; R2 is selected from a group comprising: (i) H; (ii) lower alkyl; (iii) C6-C10aryl which can be substituted with a halogen, lower alkyl, lower alkoxy group; R3 is selected from a group comprising: (i) H; (ii) lower alkyl; (iv) C3-C8cycloalkyl; R5 and R6 are independently selected from a group comprising: (i) H; (ii) lower alkyl; (iii) C3-C8cycloalkyl; (v) SO2R3; and (vi) CO2R3; R7 is selected from a group comprising H and lower alkyl; R8 is selected from a group comprising: (iii) NR5R6; (iv) lower alkyl; and n equals 1 or 2.

EFFECT: capacity to inhibit activity of cyclin-dependant kinase.

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I and to their pharmaceutically acceptable salts exhibiting inhibitory activity in relation to kinases chosen from Abl, Bcr-Abl, Bmx, BTK, b-RAF, c-RAF, CSK, cSRC, Fes, FGER3, Elt3, 1KKα, 1KKβ, JNK1α1, JNK2α2, Lck, Met, MKK4, MKK6, p70S6K, PAK2, PDGFRα, PKA, PKCα, PKD2, ROCK-II, Ros, Rsk1, SAPK2α, SAPK2β, SAPK3, SAPK4, SGK, Syk, Tie2 and TrkB. In compounds of formula I , n is equal to 1, m is equal to 0, Y1 is chosen from N and CR5, and R5 represents hydrogen, Y2 represents O, R1 represents hydrogen, R2 is chosen from hydrogen and C1-C6alkyl, R3 is chosen from a group including hydrogen, C1-C6alkyl, C1-C6alkoxy, R4 is chosen from NR5C(O)R6 and -C(O)NR5R6 where R5 is chosen from hydrogen and C1-C6 alkyl, and R6 represents phenyl optionally substituted with 1-3 radicals chosen of a group including NR3R3, halogen-substituted C1-C6alkyl, C5-C6heteroaryl(C0-C4)alkyl where heteroaryl contains 1-2 heteroatoms chosen from N and O, C5-C6heterocyclo(C0-C4)alkyl, where heterocyclyl contains 1-2 heteroatoms of N, and C5-C6heterocyclo(C0-C4)alkoxy where heterocyclyl contains 1-2 heteroatoms of N, and any heteroaryl or heterocyclyl contained in R6 is optionally substituted by 1-3 radicals independently chosen from a group including C1-C6alkyl and hydroxy(C1-C6)alkyl.

EFFECT: producing the compounds which can find application for treatment or prevention of diseases or disorders associated with abnormal or unregulated kinase activity, such as proliferative diseases, diseases of immune and nervous system.

8 cl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel chemical compound - 1-(2-isopropoxyethyl)-2-thioxo-1,2,3,5-tetrahydro-pyrrolo [3,2-d]pyrimidin-4-one and pharmaceutically acceptable salts thereof, a pharmaceutical composition containing said compounds and use thereof. Disclosed compound has myeloperoxidase enzyme inhibiting properties.

EFFECT: compounds are especially useful in treating and preventing neuroinflammatory disorders such as Parkinson's disease, cardiovascular disorders and respiratory disorders.

3 cl, 1 tbl, 33 ex

FIELD: chemistry.

SUBSTANCE: described are novel derivatives of genera formula (1) (where A denotes an oxygen or sulphur atom, -CH2- or -NH- group; R1 denotes C1-6alkyl group, possibly substituted ; R1A denotes a hydrogen atom or a C1-6 alkyl group; or these two radicals together with a carbon atom to which they are bonded form a cyclic C3-6 alkyl group; R2 denotes a C1-6 alkyl group or a C3-6 cycloalkyl group; R3 denotes an aryl group or a heteroaryl group, which can be substituted; R4 denotes a hydrogen atom; R5 denotes C1-6 alkyl group, aryl or heteroaryl group, which can be substituted), a pharmaceutical composition containing said derivatives and intermediate compounds. Said compounds (1) can inhibit bonding between SIP and its receptor Edg-1 (SIP1).

EFFECT: possibility of use in medicine.

18 cl, 2 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

and pharmaceutically acceptable salts thereof, where substitutes R1-R4 are as defined in claim 1. Said compounds have 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) enzyme inhibiting activity.

EFFECT: compounds can be used in form of a pharmaceutical composition.

15 cl, 1 tbl, 94 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new imidazopyrazines of formula where Q1 and R1 have the values specified in the patent claim, and to their pharmaceutically acceptable salts showing IGF-1R enzyme inhibiting activity and applicable for treatment and/or prevention of various diseases and conditions which are sensitive to tyrosine kinase inhibition.

EFFECT: preparation of the compounds showing IGF-1R enzyme inhibiting activity.

27 cl, 294 ex

Chemical compounds // 2405780

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I): , in which: R1 and R2 are independently specified from hydrogen, C1-6alkyl, C1-6alkoxy and cyclopropyl; X1, X2 and X3 independently represent =N- or =CR10; R3 and R10 are independently specified from hydrogen, halogen, nitro, cyano, amino, carboxy, carbamoyl, C1-6alkyl, N-(C1-6alkyl)amino, N,N(C1-6alkyl)2amino, C1-6alkanoylamino, C1-6alkoxycarbonyl; R4 represents hydrogen; R5 and R6 are independently specified from hydrogen, hydroxy and C1-6alkyl where R5 and R6 independently can be optionally substituted in carbon atom with one or more R16 where R16 represents hydroxy; A represents a single link or C1-2alkylene; where specified C1-2alkylene can be optionally substituted with one or more R18; the ring C represents a saturated, partially saturated or unsaturated mono- or bicyclic ring containing 5 or 6 atoms in which at least one atom can be specified from nitrogen, sulphur or oxygen which can be linked with carbon or nitrogen atom where the -CH2- group can be optionally substituted with -C(O)- and ring sulphur atom can be optionally oxidised to produce S-oxide; R7 is specified from halogen and C1-6alkyl where R7 can be optionally substituted in carbon atom with halogen; n is equal to 0.1 or 2; where R7 values can be equal or different; and R18 is independently specified from halogen and hydroxy; or its pharmaceutically acceptable salt. Also the invention refers to their pharmaceutical compositions and methods for preparation and application thereof for cancer treatment.

EFFECT: preparation of new compounds which can find application for cancer treatment.

23 cl, 96 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to the following compounds: N-(1-{4-[2-(1-acetylamino-ethyl)-1-ethyl-1H-imidazol-4-yl]-benzyl}-3-hydroxy-propyl)-3-chloro-4-(2,2,2,-trofluoro-1-methyl-ethoxy)-benzamide, N-(1-{4-[2-(1-methyl-1-hydroxy-ethyl)-1-ethyl-1H-imidazole-4-yl}-benzyl}-3-hydroxy-propyl)-3-chloro-4-(,2,2,2-trifluoro-1-methyl-ethoxy)-benzamide, N-(1-{4-[2-(1-hydroxy-1-methyl-ethyl)-1-methyl-1H-imidazole-4-yl]-benzyl}-3-hydroxy-propyl)-3-chloro-4-(2,2,2,-trifluoro-1-methyl-ethoxy)-benzamide, 3-chloro-N-[2-[(N,N-dimethylglicyl)amino]-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridine-2-yl]phenyl}methyl)ethyl]-4-[(1-methylethyl)oxy]benzamide, 3-chloro-N-(1-(2-(dimethylamino)acetamido)-3-(4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl)propan-2-yl)-4-isopropoxybenzamide, 3-chloro-N-(2-[(2-methylalanyl)amino]-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}ethyl)-4-[(1-methylethyl)oxy]benzamide, 3-chloro-N-[(3-hydroxy)-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridine-2-yl]phenyl}methyl)propyl]-4-[(1-methylethyl)oxy]benzamide, as well as to their pharmaceutically acceptable salts.

EFFECT: obtained compounds and salts can be used for treatment cell proliferative diseases and disorders by modulating activity of mitotic kinesin CENP-E.

26 cl, 102 ex, 7 tbl

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