Triazolo[4,5-d]pyrimidine compounds, pharmaceutical compositions based on thereof and method for treatment, method for their preparing and intermediate compounds

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

 

The text descriptions are given in facsimile form.

1. Connection triazolo[4,5-d]pyrimidine of the General formula I

where R1denotes unbranched3-5alkyl, optionally substituted by one or more halogen atoms;

R2denotes a phenyl group optionally substituted by one or more fluorine atoms;

R3and R4are both hydroxy groups;

R denotes H, where X denotes CH2, OCH2CH2or communication;

or their pharmaceutically acceptable salt, or MES or MES of such salt,

provided that:

when X is CH2or a bond, R1may not be the prop is scrap,

when X represents CH2and R1denotes CH2CH2CF3, butyl or pentyl, phenyl group, R2should be replaced by fluorine,

when X denotes co2CH2and R1- propyl, phenyl group, R2should be replaced by fluorine.

2. The compound according to claim 1, in which R1means 3,3,3-cryptochromes, non-branched butyl or unbranched propyl.

3. The compound according to claim 1 or 2, in which R2denotes phenyl or 4-forfinal or 3,4-differenl.

4. The compound according to any one of claims 1 to 3, in which R stands for CH2OH or och2CH2OH.

5. The compound according to claim 1, which is:

[1R-[1α,2A,3β(1R*,2S*),5β]]-3-[7-[[2-(4-forfinal)-cyclopropyl]amino]-5-[(3,3,3-cryptochromes)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidine-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;

[1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(3,4-differenl)-cyclopropyl]amino]-5-[(3,3,3-cryptochromes)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidine-3-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol;

[1S-(1α,2α,3β(1S*,2R*),5β]]-3-[7-[[2-(3,4-differenl)-cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo-[4,5-d]pyrimidine-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol;

[1R-[1α,2α,3β(1R*,2S*),5β]]-3-[5-(butylthio)-7-[[2-(3,4-differenl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]-pyrimidine-3-yl]-5-(GI is roximity)-cyclopentane-1,2-diol;

[1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(butylthio)-7-[[2-(4-forfinal)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidine-3-yl]-cyclopentane-1,2,3-triol;

[1S-(1α,2α,3β(1S*,2R*),5β]-3-[7-[[2-(3,4-differenl)-cyclopropyl]amino]-5-[(3,3,3-cryptochromes)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidine-3-yl]-5-(hydroxyethoxy)-cyclopentane-1,2-diol;

[1S-[1α,2α,3β,5β(1S*,2R*)]]-3-(2-hydroxyethoxy)-5-[7-(2-vinylcyclopropyl)amino]-5-[(3,3,3-cryptochromes)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidine-3-yl]-cyclopentane-1,2-diol;

[1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(butylthio)-7-[[2-(3,4-differenl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidine-3-yl]cyclopentane-1,2,3-triol;

[1S-[1α,2α,3β(1S*,2R*),5β]]-3-[5-(butylthio)-7-[(2-vinylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidine-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol; where the alkyl groups are unbranched;

or their pharmaceutically acceptable salt, or solvate, or a solvate of such a salt.

6. [1S-[1α,2α,3β(1S*,2R*),5β]]-3-[7-[2-(3,4-differenl)cyclopropyl)amino]-5-(n-propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidine-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol.

7. Pharmaceutical composition having antagonistic/agonistic activity against P2Treceptor, comprising a compound according to any one of claims 1 to 6 in combination with a pharmaceutically acceptable the first diluent, adjuvant and/or carrier.

8. Pharmaceutical composition comprising a compound according to any one of claims 1 to 6, intended for the treatment or prevention of myocardial infarction, hemorrhage, thrombotic nature of the transient disorders of cerebral circulation and/or peripheral vascular disease or prevent the growth or spread of tumors.

9. The compound according to any one of claims 1 to 6, intended for the treatment or prevention of myocardial infarction, hemorrhage, thrombotic nature of the transient disorders of cerebral circulation and/or peripheral vascular disease or prevent the growth or spread of tumors.

10. The compound according to any one of claims 1 to 6 as an active ingredient in the manufacture of a medicinal product intended for the treatment or prevention of myocardial infarction, hemorrhage, thrombotic nature of the transient disorders of cerebral circulation and/or peripheral vascular disease or prevent the growth or spread of tumors.

11. Method for the treatment or prevention of disorders mediated P2Treceptor selected from myocardial infarction, hemorrhage, thrombotic nature of the transient disorders of cerebral circulation and/or peripheral vascular disease or prevent the growth or spread what I tumors, which includes an introduction to a subject suffering from this disorder or susceptible to such condition, a therapeutically effective amount of a compound according to any one of claims 1 to 6.

12. The method of obtaining the compounds of formula (I) according to claim 1, wherein the compound of formula (II):

where R and R1defined in claim 1 and L denotes a leaving group,

subjected to interaction with [R-(R*,R*)-2,3-dihydroxybutanedioate (1:1) compounds of the formula (III):

where R2defined in claim 1,

in the presence of a base in an inert solvent at ambient temperature.

13. The compound of formula (II):

where R and R1defined in claim 1 and L denotes a leaving group.

14. The compound of formula (V):

where R1and R is defined in claim 1 and L represents a leaving group.

Priority items:

04.12.1998 according to claims 1-4, 6-14;

09.04.1999 according to claim 5.



 

Same patents:

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

SUBSTANCE: invention relates to novel hydrogenated azepino[4,3-b]indoles of the general formula (1): , their racemates, optical isomers, geometric isomers and their pharmaceutically acceptable salts and/or hydrates. In the general formula (1) a dotted line with accompanying unbroken line represents a simple or double bond; R1 and R2 represent independently of one another substitutes of amino-group chosen from hydrogen atom, possibly substituted (C1-C8)-alkyl possibly substituted with aryl, 5-6-membered azaheterocyclyl, (C1-C8)-alkoxycarbonyl, possibly substituted phenyl, possibly substituted carbonylamino- or thiocarbonylamino-group, substituted acyl, (C1-C8)-alkylsulfonyl, possibly substituted arylsulfonyl and wherein substitutes in indicated R1 and R2 are chosen independently from (C1-C8)-alkyl, halogen atoms, nitro-, carboxy-, alkoxy-group, aryl; Rin represents one or some similar or different substitutes of cyclic system chosen from hydrogen atom, (C1-C8)-alkyl, (C6-C10)-aryl, halogen atom, 5-6-membered azaheterocyclyl. Also, invention relates to methods for synthesis of these compounds, their using and pharmaceutical composition and libraries of compounds. Synthesized compounds possess neuroprotective, cognitive-stimulating and anti-histaminic properties and can be used in treatment of different neurological disorders, allergic and autoimmune diseases, for example, for memory improvement.

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

25 cl, 2 tbl, 12 ex

FIELD: medicine, pharmaceuticals.

SUBSTANCE: invention relates to compound of general formula I having structure of triazole[4,5-d]pyrimidine derivatives, or pharmaceutically acceptable salts, or prodrugs thereof. Disclosed is method for application of said compound or pharmaceutically acceptable salt thereof to produce pharmaceutical for treatment and prophylaxis of conditions ameliorated with blockage of adenosine A2A receptors. Also disclosed are pharmaceutical composition including compound of formula I, or pharmaceutically acceptable salt, or prodrug thereof in combination with pharmaceutically acceptable carrier or excipient. Said pharmaceutical compositions may be administered to subject by peroral, rectal, parantheral, transdermal, subdermal, etc. methods. Pharmaceutical of present invention are useful in treatment of Parkinson's disease, depression, cognitive or mental disturbances, acute or chronic pain, narcolepsy, etc.

EFFECT: composition of improved neuroprotective characteristics.

50 cl, 3 tbl

FIELD: organic chemistry, medicine, pharmacy, biochemistry.

SUBSTANCE: invention relates to a method for treatment of states caused by activity of p38 kinase. Method involves administration to a patient needed in this treatment of at least one compound of the formula (I): or its pharmaceutically acceptable salt or solvate wherein R3 means hydrogen atom, methyl, perfluoromethyl, methoxy-group, halogen atom, cyano-group or NH2-group; X is chosen from -O-, -OC(=O)-, -S-, -S-, -S(=O)-, -SO2-, -C(=O)-, -CO2-, -NR10-, -NR10C(=O)-, -NR10C(=O)NR11-, -NR10CO2-, -NR10SO2-, -NR10SO2NR11-, -SO2NR10-, -C(=O)NR10, halogen atom, nitro- and cyano-group, or X is absent; Z is chosen from oxygen (O), sulfur (S), nitrogen (N) atoms, and -CR20 being wherein Z means -CR20 optionally substituted bicyclic aryl or heteroaryl with R4 or R5; R1 means hydrogen atom, -CH3, -OH, -OCH3, -SH, -SCH3, -OC()=O)R21, -S(=O)R22, -SO2NR23R25, -CO2R21, -C(=O)NR24R25, -NH2, -NR24R25, -NR21SO2NR24R25, -NR21SO2R22, -NR24C(=O)R25, -NR24CO2R25, -NR21C(=O)NR24R25, halogen atom, nitro- or cyano-group; R2 is chosen from the following group: (a) hydrogen atom under condition that R2 doesn't mean hydrogen atom if X means -S(=O)-, -SO2-, -NR10CO2- or -NR10SO2-; (b) alkyl, alkenyl and alkynyl comprising up to four R26 groups or pentafluoroalkyl as substitutes; (c) aryl and heteroaryl comprising up to three groups R27 as substitutes, and (d) heterocyclo-group or heteroalkyl optionally comprising keto-group (=O), up to three groups R27 as substitutes, and/or comprising carbon-carbon bridge comprising 3-4 carbon atoms, or (e) R2 is absent if X means halogen atom, nitro- or cyano-group; R4 means substituted aryl, aryl comprising NOSE-alkyl, substituted heteroaryl or optionally substituted bicyclic 7-11-membered saturated or unsaturated carbocyclic or heterocyclic fragment as a substitute, and R5 means hydrogen atom, alkyl or substituted alkyl with exception of cases when Z means O or S and then R5 is absent, or R4 and R5 in common with Z form optionally substituted bicyclic 7-11-membered aryl or heteroaryl; R6 means hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group, substituted heterocyclo-group, -NR7R8, -OR7 or halogen atom; R10 and R11 are chosen independently from the following group: hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heterocyclo-group and substituted heterocyclo-group; R7, R8, R21, R24 and R25 are chosen independently from the following group: hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group and substituted heterocyclo-group; R20 means hydrogen, lower alkyl or substituted alkyl, or R20 can absent if carbon atom to which is bound and in common with R4 and R5 represents part of bicyclic aryl or heteroaryl; R22 means alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group or substituted heterocyclo-group; R26 is chosen from the following group: halogen atom, trifluoromethyl, halogenalkoxy-group, keto (=O)-, nitro-, cyano-group, -SR28, -OR28, -NR28R29, -NR28SO2, -NR28SO2R29, -SO2R28, -SO2NR28R29, -CO2R28, -C(=O)R28, -C(=O)NR28R29, -OC(=O)R28, -C(=O)NR28R29, -NR28C(=O)R29, -NR28CO2R29,=N-OH, =N-O-alkyl; aryl optionally comprising as a substitute from one to three R27 groups; cycloalkyl optionally comprising a substituted keto-group (=O), from one to three R27 groups, or carbon-carbon-containing bridge comprising of 3-4 carbon atoms; and heterocyclo-group comprising optionally as a substitute keto-group (=O), from one to three R27 groups or comprising carbon-carbon bridge comprising 3-4 carbon atoms, and wherein each R28 and R29 is chosen independently from the following group: hydrogen atom, alkyl, alkenyl, aryl, aralkyl, (C3-C7)-cycloalkyl and (C3-C7)-heterocycle, or they can form in common (C3-C7)-heterocycle; and each R28 and R29, in turn, can comprise optionally up to two substitutes representing alkyl, alkenyl groups, halogen atoms, halogenalkyl groups, halogenalkoxy-, cyano-, nitro-, amino-, hydroxy-, alkoxy-, alkylthio-groups, phenyl, benzyl, phenyloxy- and benzyloxy-groups; and R27 is chosen from the following group: alkyl, R32 and (C1-C4)-alkyl comprising as substitutes from one to three R32groups and wherein each R32 group is chosen independently from the following group: halogen atom, halogenalkyl, halogenalkoxy-, nitro-, cyano-groups, -SR30, -OR30, -NR30R31, -NR30SO2, -NR30SO2R31, -SO2R30, -SO2NR30R31, -CO2R30, -C(=O)R30, -C(=O)NR30R31, --OC(=O)R30, -OC(=O)NR30R31, -NR30C(=O)R31, -NR30CO2R31 and from 3-7-membered carbocyclic or heterocyclic ring comprising optionally as a substitute alkyl, halogen atom, hydroxy-, alkoxy-group, halogenalkyl, halogenalkoxy-, nitro-, amino- or cyano-group, and wherein each R30 and R31 is chosen independently from the following group: hydrogen atom, alkyl, alkenyl, aryl, aralkyl, (C3-C7)-cycloalkyl, and heterocycle, or they in common can form (C3-C7)-heterocycle. 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EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

30 cl, 14 tbl, 152 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel compound of the general formula (I): wherein R means hydrogen atom (H), -OH, carbamoyl group; n = 1 or 2, or to its pharmaceutically acceptable salt. Compounds of the formula (I) are potential inhibitors of cellular adhesion mediated by integrins that allows its using as components of pharmaceutical composition used in treatment or prophylaxis of inflammatory, autoimmune or allergic state or rejection mediated by LFA-1.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

19 cl, 2 sch, 3 dwg, 3 tbl, 7 ex

FIELD: organic chemistry, medicine, biochemistry.

SUBSTANCE: invention relates to a novel crystalline form of 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidine-1-yl}-3-oxopropionitrile. This form shows characteristic peaks in powder roentgenogram obtained by using Cu as radiation source and expressed as degrees two-theta at about 5.7; 16.1; 20.2 and 20.5. Also, invention relates to a method for preparing this form and its using in preparing medicinal agents in treatment or prophylaxis of diseases mediate by protein-tyrosine-kinases, such as JAK3. Method for preparing this form involves interaction of 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxopropionitrile with citric acid.

EFFECT: improved preparing method, valuable properties of compound.

5 cl, 1 tbl, 4 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to a novel 1,2-disubstituted derivative of imidazo[1,2-a]-benzimidazole. Invention describes 1-(3-pyrrolidinopropyl)-2-(4-fluorophenyl)imidazo[1,2-a]-benzimidazole dihydrochloride of the formula (I): Compound possesses topical anesthetizing effect in carrying out the surface (terminal) anesthesia. Invention provides preparing a novel compound possessing useful biological properties.

EFFECT: valuable medicinal property of compound.

3 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compounds of the general formula (I) wherein radical values are given in the invention claim that are novel histamine receptors antagonist. Preferable compound is 3-[2-[4-(11,12-dihydro-6H-benzimidazo]2,1-b][3]benazepin-6-yl)-2-(phenylmethyl)-1-piperidinyl]ethyl]-2,10-dimethylpyrimido[1,2-α]benzimidazole-4(10H)-one or its salts, isomers and N-oxides. Proposed compounds are useful in prophylaxis and treatment of increased intracranial pressure and/or secondary ischemia caused by craniocerebral trauma.

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

13 cl, 13 tbl, 5 dwg, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to diazacycloalkanes of the general formula (I): wherein G1 represents condensed polycyclic group. Compounds are selective and strong acting agonists of oxytocin and can useful in treatment of erectile dysfunction. Also, invention describes a pharmaceutical composition based on compounds of the formula (I) and their using in manufacturing the pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

31 cl, 136 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to a novel 1,2-disubstituted derivative of imidazo[1,2-a]imidazole. Invention describes 1-(3-diethylaminopropyl)-2-4-fluorophenyl)-imidazo[1,2-a]benzimidazole of the formula (I): . Compound elicits local anesthetic effect in surface (terminal), infiltration, conduction and epidural anesthesia. Invention provides synthesis of a novel compound possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds.

6 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of diazabicyclic alkanes of the formula (1) and their pharmaceutically acceptable salts and stereoisomers wherein R1 means phenyl, 3-indolyl or benzo[b]thiophene-3-yl and wherein indicated phenyl group can be substituted with halogen atom; R2 and R3 represent independently halogen atom, -CH3 or -CF3; R4 represents hydrogen atom (H), hydroxyl group (-OH), -CH2OH, -NH2, dialkyl-(C1-C3)-N, pyrrolidine-1-yl, piperidine-1-yl, morpholine-4-yl or morpholine-4-yl substituted with one or two methyl or methoxymethyl groups, morpholine-4-ylamino-group, morpholine-4-ylmethyl, imidazole-1-yl, thiomorpholine-4-yl, 1,1-dioxothiomorpholine-4-yl or 3-oxa-8-azabicyclo[3.2.1]oct-8-yl; R5 means hydrogen atom; R4 and R5 can represent in common keto-group, 1,3-dioxane-2-yl or 1,3-dioxalane-2-yl; R6 represents H, morpholine-4-yl substituted with methyl group or -CH2OH wherein indicated group -CH2OH can form ester with organic acid; X represents oxygen atom (O); n = 1 or 2. Proposed compounds possess antagonistic activity with respect to NK1-receptors. Also, invention describes intermediate compounds used in synthesis of compounds of the formula (I), pharmaceutical composition and using compounds in preparing drugs in treatment, for example, such diseases as chronic pains, inflammatory diseases and disorders of the central nervous system.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

7 cl, 6 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

The invention relates to new compounds of General formulas I, II, III

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or their pharmaceutically acceptable salts, in which the dotted lines indicate optional double bonds; A is-CR7or N; - - NR1R2, -CR1R2R11, -C(= CR2R12R1, -NHCHR1R2, -ОСHR1R2, -SCHR1R2, -CHR2OR12,

-CHR2SR12, -C(S)R2or-C(O)R2N-ethyl-2,2,2-triptorelin; G is oxygen, sulfur, NH, NH3hydrogen, methoxy, ethoxy, triptoreline, methyl, ethyl, dimethoxy, NH2, NHCH3N(CH3)2or trifluoromethyl; Y Is N; Z is NH, O, S, -N(C1-C2alkyl) or-C(R13R14), where R13and R14independently of one another represent hydrogen, trifluoromethyl or methyl, or one of the elements of R13and R14is cyano and the other is hydrogen or stands; R1- C1-C6alkyl which may be optionally substituted by one or two substituents R8independently from each other selected from the group comprising hydroxy, fluorine, chlorine, bromine, iodine, CF3C1-C4alkoxy, -O-CO-(C1-C4alkyl), where (C1-C2- C1-C12alkyl, aryl or -(C1-C4alkylene)aryl, where aryl is phenyl, naphthyl; R3is methyl, ethyl, fluorine, chlorine, bromine, iodine, cyano, methoxy, OCF3, methylthio, methylsulphonyl, CH2HE or CH2OCH3; R4is hydrogen, C1-C4alkyl, fluorine, chlorine, bromine, iodine, C1-C4alkoxy, triptoreline, -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3, -CF3, amino, nitro, -NH(C1-C4alkyl), -N(CH3)2, -NHCOCH3, -NHCONHCH3, hydroxy, -CO(C1-C4alkyl), -Cho, COOH, cyano, or-COO(C1-C4alkyl), where C1-C4the alkyl may be substituted by one Deputy chosen from the group comprising hydroxy, amino, -NHCOCH3, -NH(C1-C2alkyl), -N(C1-C2alkyl)2, fluorine, chlorine, cyano, nitro; R5is phenyl, naphthyl, pyridyl, pyrimidyl, where each of the above groups R5substituted with one to three substituents that are independently from each other selected from fluorine, chlorine, C1-C6the alkyl or C1-C6alkoxyl, or one Deputy chosen from the group comprising hydroxy, iodine, bromine, formyl, cyano, nitro, trifluoromethyl, amino, -(C1-C6these groups of R5may be optionally substituted with one hydroxy-group; R6is hydrogen or C1-C6alkyl; R7is hydrogen, methyl; R11is hydrogen, hydroxy, fluorine or methoxy; R12is hydrogen or C1-C4alkyl, and R16and R17independently of one another represent hydrogen, hydroxy, methyl, ethyl, methoxy or ethoxy, except that both R16and R17cannot both be methoxy or ethoxy; or R16and R17together form oxo (=O) group; provided that if G is an atom of oxygen, sulfur, NH or NCH3he is joined by a double bond to a five-membered ring of the formula III, and further provided that R6is absent when the nitrogen atom to which it is linked, is attached by a double bond to an adjacent carbon atom in the ring

The invention relates to new substituted aminomethanesulfonic General formula (I) possessing a highly effective herbicide action, as well as the way they are received, herbicide tool based on these intermediate compounds of General formula (II)

The invention relates to new derivatives of arylethanolamine formula I or its pharmaceutically acceptable salts, which have a high affinity for endothelin and can find application in medicine

The invention relates to new derivatives of glycinamide formula (I), which, as agonists of the receptors, cholecystokinin, can be used in pharmaceuticals, which allows to treat some digestive disorders, obesity, psychosis and other
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