Trisubstituted urea as cytokine inhibitors

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

 

The text descriptions are given in facsimile form.

1. Connection, including all enantiomers and pharmaceutically acceptable salts, and the said compound has the formula:

where R is unsubstituted or substituted-HE1-4the alkyl or-O-C1-4a linear alkyl or branched alkyl With1-C4;

R1has the formula:

-(L)x-R3,

R3is a fragment selected from the group consisting of substituted or unsubstituted fanilow where the Deputy is selected from the group1-4alkyl, -O-C1-4alkyl, -S-C1-4alkyl or fluorine;

R2has the formula:

-(L1/sup> )y-R4,

R4is a fragment selected from the group consisting of:

(i) a hydrogen atom;

ii) substituted by-OH, -O-C1-4the alkyl or phenyl, or unsubstituted linear or branched hydrocarbon C1-C10where hydrocarbon represents a C1-6alkyl;

L and L1are bridge fragments-NR5-;

each of the fragments of R5is a hydrogen atom, a linear or branched alkyl With1-C4;

the indices x and y can independently be 0 or 1.

2. The compound according to claim 1, where R is alkyl fragment With1-C4selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl.

3. The compound according to claim 1, where R is a substituted alkyl fragment With1-C4selected from-CH2HE, -CH2Och3, -CH2CH2HE, -CH2CH2Och3, -CH2CH2CH2HE.

4. The compound according to claim 1, where R1has the formula:

-(L)x-R3,

the index x is equal to O, R3is selected from 4-methoxyphenyl, 4-ethoxyphenyl, 4-ftoheia, 4-methylphenyl and 4-methylsulfinylphenyl.

5. The compound according to claim 1, where R2is selected from (S)-2-hydroxy-1,2-dimethylpropylene group, (S)-2-methoxy-1-methylethylamine-group (S)1 phenylethylamine group, and isopropylamino group.

6. Connection, selectable from:

1-(4-methoxyphenyl)-1-{2-[(1S)-2-methoxy-1-methylethylamine]pyrimidine-4-yl}-3-utilmately;

1-(4-methoxyphenyl)-1-{2-[(1S)-2-methoxy-1-methylethylamine]pyrimidine-4-yl}-3-mutilation;

1-(4-ethoxyphenyl)-1-{2-[(1S)-2-methoxy-1-methylethylamine]pyrimidine-4-yl}-3-utilmately.

7. Pharmaceutical composition having the property of inhibiting cytokines, including:

a) an effective amount of one or more compounds according to any one of claims 1 to 6,

b) one or more pharmaceutically compatible excipients.

8. The use of compounds according to claim 1 for the manufacture of a medicinal product for the treatment of diseases mediated by the activity of inflammatory cytokines, such as arthritis.

9. The method of synthesis trehzameshchenny urea, including:

a) chemical interaction of 2,4-diaminopirimidina having the formula:

with bis-trimethylsilyl-trifurcation, leading to the formation of in situ activated 2,4-diaminopirimidina; and

6) chemical interaction mentioned activated 2,4-diaminopirimidina formed in situ on the stage (a), with an isocyanate having the formula:

OCN-R,

leading to the formation of trehzameshchenny urea, having the forms of the Lu:

where R, R1and R4have the meanings indicated in claim 1.

10. The method of synthesis trehzameshchenny urea, including:

a) chemical interaction of 2,4-diaminopirimidina with an amine having the formula:

R1-NH2,

in the presence of NaHCO3where R1matter specified in claim 1, to obtain 2-chloro-4-aminopyrimidine having the formula:

b) chemical interaction of 2-chloro-4-aminopyrimidine with an amine having the formula:

R4-NH2,

where R4matter specified in claim 1,

to obtain 2,4-diaminopirimidina having the formula:

C) processing the obtained 2,4-diaminopirimidina oxalic acid, which is formed oxalate 2,4-diaminopirimidina;

g) processing the received oxalate 2,4-diaminopirimidina bis-trimethylsilyl-trifurcation, with the production of activated 2,4-diaminopirimidina; and

d) processing the obtained activated 2,4-diaminopirimidina an isocyanate having the formula:

OCN-R,

where R has the meanings indicated in claim 1, obtaining trehzameshchenny urea having the formula:



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention pertains to new compounds with general formula: , where R is -(CH2)n-A, where A: where each of B and C independently represent phenyl or phenyl substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, -OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NH-C(O)-(C1-C6alkyl) and -NO2; or n equals an integer from 0 to 3; n1 equals an integer from 1 to 3; n2 equals an integer from 0 to 4; n3 equals an integer from 0 to 3; n4 equals an integer from 0 to 2; X1 is chosen from a chemical bond -S-, -S(O)2-, -NH-, -NHC(O)- and -C=C-, R1 is chosen from C1-C6alkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, tetrahydropyranyl, CN, -N(C1-C6alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, naphtyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolydinyl, thiomopholinyl, tetrazolyl, benzoxazolyl, imidazolidine-2-thionyl, 7,7-dimethylbicyclo[2.2.1]heptane-2-onyl, benzo[1.2.5]oxadiazolyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and pyrrolyl, each of which can be optionally substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NO2, -SO2(C1-C3alkyl), -SO2NH2, -SO2N(C1-C3alkyl)2, -COOH, -CH2-COOH, pyridyl, 2-methylazolyl, morpholino, 1-chloro-2-methylpropyl, phenyl, (optionally substituted with one or more halogens), benzyloxy, and , X2 selected from -O-, -CH2-, -S-, -SO-, -SO2-, -NH- and , R2 represents a ring group, chosen from a phenyl or thienyl group. Each ring group is substituted with a group with formula -(CH2)n4-CO2H; and besides that, the ring group can optionally be substituted with 1 or 2 extra substitutes, independently chosen from halogen, - C1-C6alkyl and -C1-C6alkoxy; R3 is chosen from H, halogen and -NO2; R4 is chosen from H, halogen and morpholino; or its salt form, used in pharmaceuticals. The invention also relates to pharmaceutical compositions, to methods of treatment, and to compounds with formula (A).

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on them, which have inhibiting effect on cytosolic phospholipase A2.

45 cl, 300 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new nitrogen-containing heterocyclic derivatives represented by the formula (I): where symbols have the following meaning: R1 and R2 can be equal or different and denote H-, C1-C6-alkyl, C3-C14-cycloalkyl, C1-C6-alkyl-CO-, HO-CO-, C1-C6-alkyl-O-CO-, H2N-CO-, C1-C6-alkyl-HN-CO-, (C1-C6-alkyl)2N-CO-, C1-C6-alkyl-O-, C1-C6-alkyl-CO-O-, H2N-, C1-C6-alkyl-HN-, (C1-C6-alkyl)2N-, C1-C6-alkyl-CO-NH-, halogen, nitro, morpholine, pyrrolidin, imidazol or cyano; R3 and R4 can be equal or different and denote C1-C6-alkyl, C1-C6-alkyl-O-, (C1-C6-alkyl)2N- or halogen; R5 and R6 can be equal or different and denote H-, C1-C6-alkyl or halogen; R7 and R8 can be equal or different and denote H-, C1-C6-alkyl, HO-, C1-C6-alkyl-O- or halogen; R7 and R8 together can form oxo (O=); R9 denotes heterocyclic group -C1-C6-alkyl-CO-, which can be optionally substituted for at least one substitute selected out of a group b described further, where heterocyclic group is selected out of morpholine, piperazine, pyrrolidin, piperidine, thiomorpholine, azepine, diazepine, oxyazepine, decahydroquinoline, decahydroisoquinoline, hexahydroazepine or 2,5-diazabicyclo[2.2.1]heptane; R10, R11, R12 and R13 can be equal or different and denote H- or C1-C6-alkyl; group b: (1) HO, (2) C1-C6-alkyl-O-, (3) R101 R102N (where R101 and R102 can be equal or different and denote (i) H, (ii) C1-C6-alkyl), (4) halogen, (5) oxo (O=), (6) C3-C14-cycloalkyl, (7) phenyl, (8) pyrrolidine, (9) C1-C6-alkyl, which can be optionally substituted for HO, C1-C6-alkyl-O-, phenyl, C1-C6-alkyl-CO- or morpholine, (10) acyl, which can be optionally substituted for oxo (O=), where acyl is C1-C6-alkyl-CO- or heterocyclic -CO group, where heterocyclic group is imidazol, pyridine or pyrazine, (11) H2N-CO- and (12) C1-C6-alkyl-SO2; A denotes heterocycloalkyl group selected out of piperidine, pyrrolidine or hexahydroazepine; n is 0, or its pharmaceutically acceptable salts. The invention also concerns pharmaceutical composition and application of nitrogen-containing heterocyclic derivatives from each of pp. 1-11.

EFFECT: obtaining new biologically active compounds and pharmaceutical composition based on there, with inhibition effect on sodium channel activity.

16 cl, 226 ex, 32 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: derivatives possess antiproliferative activity and stimulate an apoptosis in cells where absence of normal regulation of development of a cell and its destruction is observed. The derivatives are applied as a part of pharmaceutical compositions in combination with pharmaceutically acceptable mediums. The pharmaceutical compositions can be applied for treatment of diseases caused by hyperproliferation, including tumour growth, lymphoproliterative diseases and angiogenesis. Invention compounds pertain to the group of replaced pyrazoles and Pyrazolinums characterised by the formula of the invention.

EFFECT: derivatives possess useful biological properties.

56 cl, 115 ex

FIELD: chemistry.

SUBSTANCE: invention concerns malonamide derivatives of the formulae (IA) or (IB) , and pharmaceutically acceptable acid additive salts of them, where R1, R1',(R2)1,2,3, R3, R4, R14, L, and are such as described in this invention. Also the invention concerns a medicine with inhibition effect on γ-secretase, which can be applied in treatment of Alzheimer's disease.

EFFECT: obtaining new malonamide derivatives with beneficial biological properties.

17 cl, 188 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: chemistry.

SUBSTANCE: invention relates to new compounds with the general formula (I) in the racemic, enantiomeric form or in any combination of these forms and in which: A represents -CH2-, -C(O)-, -C(O)-C(Ra)(Rb)-; X represents -CH-; Ra and Rb independently represent the hydrogen atom or a radical (C1-C6)alkyl; Rj represents the atom of hydrogen; a radical (C1-C8)alkyl, not necessarily substituted hydroxyl or by one or more identical or different radicals of halogens; (C2-C6)alkenyl; or a radical of the formula -(CH2)n-X1; R2 represents a radical (C1-C8)alkyl not necessarily substituted hydroxyl or by one or more identical or different radicals of halogens; (C2-C6)alkenyl; or a radical of the formula -(CH2)n-X1; each X1 independently represents (C1-C6)alkoxy, (C3-C7)cycloalkyl or heteroaryl, and radicals (C3-C7)cycloalkyl, aryl and heteroaryl are not necessarily replaced by one or more either identical or various assistants chosen from: -(CH2)n'-V1-Y1, halogen and; V1 represents -O-, -S- or a covalent bond; Y1 represents a radical (C1-C6)alkyl, not necessarily substituted hydroxyl or by one or more identical or different radicals of halogens; n represents an integer from 0 up to 6 and n ' - an integer from 0 up to 2 that if n is equal 0 then X1 does not represent a radical alkoxy); or R1 and R2 form together with the atom of nitrogen to which they are attached, heterobicycloalkyl or heterocycloalkyl, are not necessarily replaced by one or more either identical or various substitutes chosen from: hydroxy, (C1-C6)alkyl, not necessarily substituted by hydroxy, (C1-C6)alkoxycarbonyl, heterocycloalkyl and-C(O)NV1'Y1', in which V1' and Y1' independently represent the atom of hydrogen or (C1-C6)alkyl; or R1 and R2 together form a radical of the formula: R3 represents-Z3, -C(RZ3)(R'Z3)-Z3, -C(RZ3)(R'Z3)-(CH2)p-Z3 or -C(O)Z'3; RZ3 and R'Z3 independently represent atom of hydrogen or a radical (C1-C6)alkyl; Z3 represents Z3b, Z3c, Z3d or Z3e; Z3b represents (C1-C6)alkoxy, (C1-C6)alkythio, (C1-C6)alkylamino, or a radical di((C1-C6)alkyl) amino; Z3c represents aryl or a radical heteroaryl; Z3d represents C1-C6)alkoxycarbonyl, aminocarbonyl, (C1-C6)alkylaminocarbonyl, di((C1-C6)alkyl) aminocarbonyl, (C1-C6)alkyl-C(O)NH-, (C3-C7) cycloalkyl, heterocycloalkyl; and radicals (C3-C7) cycloalkyl and heterocycloalkyl are not necessarily replaced by one or more either identical or various substitutes chosen from: (C1-C6)alkoxy, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl and oxy, radicals aryl and heteroaryl are not necessarily replaced by one or more either identical or various substitutes chosen from: halogen, cyanogen, nitro, azide, oxy, (C1-C6)alkylcarbonyl-(C1-C6)alkenyl, (C1-C6)alkylaminocarbonyl-(C1-C6)alkenyl, -SO2-NR31R32, heterocycloalkyl, heteroaryl or -(CH2)P'-V3-Y3; R31 and R32 form together with atom of nitrogen to which they are attached, heterocycloalkyl, V3 represents -O-, -S-, -C(O)-, -C(O)-O-, -O-C(O)-, -SO2-, -SO2NH-, -NR'3-SO2-, -NR'3-, -NR'3-C(O)-, -C(O)-NR'3-, -NH-C(O)-NR'3- or covalent bonds; Y3 represents the atom of hydrogen; radical (C1-C6)alkyl, not necessarily replaced by one or more either identical or different radicals of halogens; radical aryl or a radical aryl-(C1-C6)alkyl; Z3e represents a radical of the formula

, Z'3 represents a radical aryl, not necessarily replaced by one or more oreither identical or various substitutes chosen from: halogen, nitro and -(CH2)P"-V'3-Y'3; V'3 represents -O-, -C(O)-, -C(O)-O, -C(O)-NR'3-,-NH-C(O)-NR'3- or covalent bonds; Y'3 represents the atom of hydrogen or a radical (C1-C6)alkyl, not necessarily replaced by one or more either identical or different radicals of halogens; R'3 represents the atom of hydrogen (C1-C6)alkyl or a radical (C1-C6)alkoxy; p represents an integer from 1 up to 4; p' and p" independently represent an integer from 0 up to 4; R4 represents a radical of the formula -(CH2)S-R'4; R'4 represents a radical guanidine; heterocycloalkyl containing, at least, one atom of nitrogen and not necessarily substituted (C1-C6)alkyl or aralkyl; heteroaryl containing, at least, one atom of nitrogen and not necessarily substituted (C1-C6)alkyl or a radical of the formula -NW4W'4; W4 represents an atom of hydrogen or (C1-C8) alkyl; W'4 represents a radical of the formula -(CH2)S-Z4; Z4 represents an atom of hydrogen (C1-C8) alkyl, (C3-C7)cycloalkyl, heteroaryl and aryl; s and s' independently represent an integer from 0 up to 6; and i) if R3 represents -C(O)-Z'3 and R4 represents a radical of the formula -(CH2)S-NW4W'4, and W4 and W'4 independently represent an atom of hydrogen or a radical C1-C6)alkyl, then -(CH2)s represents neither radical ethylene nor radical -(CH2)-CH((C1-C4)alkyl) and ii), if R3 represents -Z3c and Z3c represents phenyl or naphthyl, then phenyl and naphthyl are not substituted by cyanogen; also note that if R3 represents -Z3d, then Z3d, represents only one (C3-C7)cycloalkyl or heterocycloalkyl; or to their pharmaceutically acceptable salts. The invention also relates to the method of obtaining the compounds of the formula (I), to a pharmaceutical composition, and to the application of compounds of the formula (I) and (I ').

EFFECT: obtaining new biologically active compounds on their basis, possessing activity with respect to receptors MC4.

41 cl, 535 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the tetrahydroquinolin derivatives with the common formula (I) or their pharmaceutically acceptable salts, where R1 and R2 are H or Me; R3 is H, hydroxy or (1-4C)alkoxi; R4 is H, OH, (1-4C)alkoxi; R5 is OH, (1-4C)alkoxi or R7; provided the R4 is H, then R5 differs from OH or (1-4C)alkoxi; R6 is (2-5C)heteroaryl, not necessarily substituted with one or more substitutes, selected from (1-4C)alkyla, bromine or chlorine; (6C)aryl, not necessarily substituted with one or more substitutes, selected from (1-4C)alkyla, (1-4)C-alkoxi, bromine, chlorine, phenyl or (1-4C) (di)alkylamino; (3-8C)cycloalkyl, (2-6C)heterocycloalkyl or (1-6C)-alkyl; R7 is amino, (di)(1-4C)alkylamino, (6C)arylcarbonylamino, (2-5C)heteroarylcarbonylamino, (2-5C)heteroaryl-carbonylokxi, R8-(2-4C)alkoxi, R9-methylamino or R9-methoxi; R8 is amino, (1-4C)alkoxi, (di)(1-4C)-alkylamino, (2-6C)-heterocycloalkyl, (2-6C)heterocycloalkylcarbonylamino or (1-4C)-alkoxicarbonylamino; and R9 is aminocarbonyl, (di)(1-4C)alkylaminocarbonyl, (2-5C)heteroaryl or (6C)aryl. The invention also relates to the pharmaceutical composition which contains the said derivatives, and to the application of the derivatives in fertility modulating.

EFFECT: novel tetrahydroquinolin derivatives with follicle-stimulating hormone receptors modulating activity are obtained.

15 cl, 51 dwg

FIELD: chemistry.

SUBSTANCE: invention refers to new pyridazine -3 (2H) derivatives, the chemical formula of which corresponds to the general formula , in which R1, R2, R3, R4 and R5 have values indicated in the formula of the invention. The compounds of the formula (I) are effective and selective inhibitors of phosphodiesterase 4. The invention also refers to the method of their preparation, pharmaceutical composition which includes these compounds, and to the application for medicine preparation for treatment of disease state or disease which medicable by meance of phosphodiesterase 4 inhibition. Besides, the object of the invention is the method of disease state and disease treatment by means of phosphodiesterase 4 inhibition.

EFFECT: new compounds have effective biological properties.

19 cl, 25 tbl, 278 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of N-form hydroxylamine of the formula (I) where X means -CH2-, -CH(OH)-, -CH(OR)-,-CF2- or -CH(F) - where R meansC1-C7alkyl, R1 means phenyl, quinoline, izo quinoline, pyridyl oxypyridyl, unessentially replaced by substitutesR6, R7, R8, R9, or means a structural fragment of the formula where each of R10 and R11 independently means H, halogen; everyoneR2, R3, R4, R5 independently means H, C1-C7alkyl, n is equal to 0-2 provided that if n is equal to 0 Xmeans-CH2 everyone of R6, R7, R8, R9 H, OH independently means, halogen, C1-C7alkyl, replaced by halogen C1-C7alkyl, C1-C7alkoxy, phenyl or its pharmaceutically acceptable salt.

EFFECT: compounds display high anti-bacteria activity.

12 cl, 1 tbl, 50 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to drugs and concerns using (2R,4R)-2-({[5-(4-fluorophenyl)-pyridin-3-ylmethyl]-amino}-methyl)-chroman-4-ol or its pharmaceutically acceptable salts or solvates used for production of a drug for treatment of catalepsy. Also, invention proposes a pharmaceutical composition for treatment of catalepsy that comprises (2R,4R)-2-({[5-(4-fluorophenyl)-pyridin-3-ylmethyl]-amino}-methyl)-chroman-4-ol as an active component taken in the pharmaceutically effective amount in combination with one or some pharmaceutically acceptable excipients.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

3 cl, 15 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

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of pyrimidine of the general formula (I): or its pharmaceutically acceptable salts or esters hydrolyzed in vivo and possessing properties of selective inhibitor of cyclin-dependent kinases, such as CDK-2, and inhibiting proliferation of cells. Compounds can be used in preparing medicinal agents used in treatment of cancer diseases. In compounds of the formula (I) R1 represents halogen atom; p = 0 or 1; R2 represents sulfamoyl or group B-E-; q = 0 or 1 wherein p + q = 1; R3 represents hydrogen atom, (C1-C6)-alkyl wherein R3can be substituted optionally at carbon atom with one or some M; R4 represents (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl wherein R4 can be substituted optionally with one or some M; or R3 and R4 taken with nitrogen atom to which they are bound form heterocyclic ring substituted optionally at carbon atom with one or some M wherein if indicated heterocyclic ring comprises group -NH then nitrogen atom can be substituted optionally with group chosen from Q; B is chosen from (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C6)-alkyl, phenyl-(C1-C6)-alkyl or (heterocyclic group)-(C1-C6)-alkyl wherein B can be substituted optionally at carbon atom with one or some D and wherein indicated heterocyclic group comprises group -NH- then nitrogen atom can be substituted optionally with group chosen from G; E represents -S(O)r- or -N(Ra)SO2- wherein Ra represents hydrogen atom or (C1-C6)-alkyl and r = 2; D is chosen independently from halogen atom, nitro-, cyano-, hydroxy-, amino-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-, N-(C1-C6)-alkylamino-, N,N-((-C1-C6)-alkyl)2-amino-, (C1-C6)-alkanoylamino-group, (C1-C6)-alkyl-S(O)a wherein a = 0-2, wherein D can be substituted optionally at carbon atom with one or some V; M is chosen independently from halogen atom, nitro-, cyano-, hydroxy-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-, N,N-((C1-C6)-alkyl)2-amino-group, (C1-C6)-alkoxycarbonyl, (C3-C8)-cycloalkyl or heterocyclic group wherein M can be substituted optionally at carbon atom with one or some P; P, X and Y are chosen independently from hydroxy-group, methyl, methoxy-, dimethylamino-group; G and Q are chosen independently from (C1-C4)-alkyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkoxycarbonyl wherein Q can be substituted optionally at carbon atom with one or some X. Also, invention relates to methods for synthesis of compounds, preparing pharmaceutical compositions based on thereof and to a method for inhibition of proliferation of cells.

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

15 cl, 2 sch, 133 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention elates to novel derivatives of uracil of the formula [I] possessing herbicide activity, a herbicide composition based on thereof and to a method for control of weeds. In derivatives of uracil of the formula [I] the group Q-R3 represents a substituted group taken among:

wherein a heterocyclic ring can be substituted with at least a substitute of a single species taken among the group involving halogen atom, (C1-C6)-alkyl-(C1-C6)-alkoxy; Y represents oxygen, sulfur atom, imino-group or (C1-C3)-alkylimino-group; R1 represents (C1-C3)-halogenalkyl; R2 represents (C1-C3)-alkyl; R3 represents OR7, SR8 or N(R9)R10; X1 represents halogen atom, cyano-group, thiocarbamoyl or nitro-group; X2 represents hydrogen or halogen atom wherein each among R7, R8 and R10 represents independently carboxy-(C1-C6)-alkyl and other substitutes given in the invention claim; R9 represents hydrogen atom or (C1-C6)-alkyl. Also, invention relates to intermediate compounds used in preparing uracil derivatives.

EFFECT: improved preparing method, valuable properties of compounds.

40 cl, 16 sch, 12 tbl, 65 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of 5-phenylpyrimidine or their pharmaceutically acceptable acid-additive salts that elicit properties of antagonists of neuropeptide receptor neurokinin-1 (NK-1). This allows their applying for treatment of such diseases as Alzheimer's disease, cerebrospinal sclerosis, attenuating syndrome in morphine withdrawal, cardiovascular alterations and so on. Compounds of invention correspond to the general formula (I):

wherein R1 means hydrogen or halogen; R2 means hydrogen, halogen atom, (lower)-alkyl or (lower)-alkoxy-group; R3 means halogen atom, trifluoromethyl group, (lower)-alkoxy-group or (lower)-alkyl; R4/R4' mean independently hydrogen atom or (lower)-alkyl; R5 means (lower)-alkyl, (lower)-alkoxy-group, amino-group, hydroxyl group, hydroxy-(lower)-alkyl, -(CH2)n-piperazinyl substituted optionally with lower alkyl, -(CH)n-morpholinyl, -(CH2)n+1-imidazolyl, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl, (lower)-alkylsulfanyl, (lower)-alkylsulfonyl, benzylamino-group, -NH-(CH2)n+1N(R4'')2, -(CH2)n-NH-(CH2)n+1N(R4'')2, -(CH2)n+1N(R4'')2 or -O-(CH2)n+1N(R4'')2 wherein R4'' means hydrogen atom or (lower)-alkyl; R6 means hydrogen atom; R2 and R6 or R1 and R6 in common with two ring carbon atoms can represent -CH=CH-CH=CH- under condition that n for R1 is 1; n means independently 0-2; X means -C(O)N(R4'')- or -N(R4'')C(O)-. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds.

15 cl, 4 sch, 86 ex

The invention relates to new derivatives of 4-phenylpyrimidine and their pharmaceutically acceptable acid additive salts, which possess the properties of receptor antagonists neirokinina(NK-1), and can be used to treat diseases, oposredstvovanii NK-1 receptor, for example, headache, Alzheimer's disease, multiple sclerosis, cardiovascular changes, oedema, chronic inflammatory diseases and so on

The invention relates to new nitrogen-containing aromatic 6-membered cyclic compounds of the formula (I) or their pharmaceutically acceptable salts, demonstrating excellent selective PDE V inhibitory activity

FIELD: medicine; pharmacology.

SUBSTANCE: agent possessing wound-healthing, antiinflammatory, antibacterial, immunomodulating, anaesthetising and antitumoral activity on a basis of terpenoids, contains a capsule extract of plants of Pinaceae bloodline exposed to short-term stressful influence, enriched with monoterpenes, obtained from a capsule extract. The pharmaceutical composition possessing wound-healthing, antiinflammatory, antibacterial, immunomodulating, anaesthetising and antitumoral activity, contains the above described agent in effective quantity and the target additive. Application of the above described agent for preparation of a medicinal preparation for treatment of pyoinflammatory diseases.

EFFECT: increased wound-healthing; antiinflammatory; antibacterial; immunomodulating; anaesthetising and antitumoral activities.

8 cl, 1 dwg, 6 tbl, 8 ex

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