Method for preparing 3-{2-[4-(6-fluorobenzo[d]isoxazole-3-yl)piperidine-1-yl]ethyl}-2-methyl-6,7,8,9-tetrahydro-4h-pyrido[1,2-a]pyrimidine-4-one, intermediate derivatives for its preparing and method for preparing intermediate derivative

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to a method for preparing a pharmaceutically active compound 3-{2-[4-(6-fluorobenzo[d]isoxazole-3-yl)piperidine-1-yl]ethyl}-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-4-one (risperidone) of the formula (I): that possesses the neuroleptic properties. Method involves the condensation reaction of (2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-yl)acetaldehyde of the formula (II): with (6-fluoro-3-piperidinyl)-1,2-benzisoxazole of the formula (IV): to yield intermediate enamine representing 3-{2-[4-(6-fluorobenzo[d]isoxazole-3-yl)piperidine-1-yl]vinyl}-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-4-one of the formula (III): and the following reduction of this enamine in the presence of hydride. Also, invention claims intermediate compounds of the formula (II) and formula (III) and describes a method for preparing compound of the formula (II) comprising oxidation of 3-(2-hydroxyethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-4-one of the formula (X): Method is characterized by high reproducibility in large-scale manufacturing and represents the unique combination of the synthesis simplicity, decreased cost, safety and protection of the environment.

EFFECT: improved preparing method.

9 cl, 3 ex

 



 

Same patents:

FIELD: organic chemistry of heterocyclic compounds, pharmacy.

SUBSTANCE: invention relates to new bicyclic heteroaromatic compounds of the general formula (I): wherein R1 represents phenyl optionally substituted with NHR5 or OR5; R2 represents (C1-C4)-alkyl or phenyl; R5 represents phenylcarbonyl, (C4-C6)-heterocycloalkylcarbonyl, (C2-C8)-alkenylsulfonyl and others; Y represents nitrogen atom (N); Z represents -NH2 or -OH. A represents sulfur atom (S) or a bond; B represents -N(H) or oxygen atom (O); X1-X2 represent C=C, -NH-C(O), C=N and others; Proposed compounds show agonistic activity with respect to LH receptor and can be used in medicine.

EFFECT: valuable medicinal properties of compounds.

10 cl, 34 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of β-carboline of the general formula (I)

showing properties of phosphodiesterase V inhibitor (PDE V). In the general formula (I) R1 means hydrogen atom; n = 0; X is taken among the group consisting of oxygen (O), sulfur (S) atoms and NRD; R2 is taken among the following group: phenyl (that can be optionally substituted with 1-3 RB), 6-membered nitrogen-containing heteroaryl and 5-6-membered heterocycloalkyl comprising 1-2 oxygen atoms and condensed with benzene ring (optionally substituted with 1-3 RB); R4 is taken among the group consisting of hydrogen atom, carboxy-group. (C1-C6)-alkylcarbonyl, di-[C1-C8)-alkyl]-aminoalkoxycarbonyl, di-[(C1-C8)-alkyl]-amino-(C1-C8)-alkylaminocarbonyl; a = a whole number from 0 to 1; Y is taken among the group consisting of -CH2, -C(O); Z is taken among the group consisting of -CH2, -CHOH, and -C(O) under condition that when Z represents -CHOH or -C(O) then X represents -NH; is taken among the group consisting of naphthyl, 5-6-membered heteroaryl comprising 1-3 heteroatoms taken among nitrogen, oxygen and/or sulfur atoms possibly condensed with benzene ring; m = a whole number from 0 to 2; R3 is taken independently among the group consisting of halogen atom, nitro-group, (C1-C8)-alkyl, (C1-C8)-alkoxy-group, trifluorophenyl, phenyl (optionally substituted with 1-3 RB), phenylsulfonyl, naphthyl, (C1-C8)-aralkyl, 5-6-membered heteroaryl comprising 1-3 nitrogen atoms in the ring (optionally substituted with 1-3 RB). Also, invention relates to a pharmaceutical composition, a method for its preparing and methods for inhibition of phosphodiesterase V activity (PDE V), and for increase of the cGMP concentration.

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

14 cl, 11 sch, 7 tbl, 13 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of pyridopyrimidines of the formula (I): or (II): wherein Z means nitrogen atom (N) or -CH; W means -NR2; X1 means oxygen atom (O), -NR4 (wherein R4 means hydrogen atom or alkyl), sulfur atom (S) or -CR5R6 (wherein R5 and R6 mean hydrogen atom); X2 means oxygen atom (O); Ar1 means unsubstituted or substituted phenyl; R2 means hydrogen atom, alkyl or acyl; R1 means hydrogen atom, alkyl, halide alkyl and others; R3 means alkyl; cycloalkyl and others; R8 and R9 mean hydrogen atom, alkylsulfonyl and others, and to their pharmaceutically acceptable salts, and to intermediate compounds that are used for preparing compounds of the formula (I) and (II). Indicated compounds show inhibitory activity with respect to activity of p38 kinase and can be used in preparing a medicine agent for treatment of p38-mediated disturbances.

EFFECT: improved preparing methods, valuable medicinal properties of compounds and composition.

38 cl, 3 tbl, 116 ex

FIELD: biochemistry, medicine, in particular new bioactive compounds having peptide hormone vasopressin agonistic activity.

SUBSTANCE: disclosed are compounds of general formula 1 or 2 or tautomers, or pharmaceutically acceptable salts thereof, wherein W represents N or C-R4; R1-R4 are independently H, F, Cl, Br, alkyl, O-alkyl, NH2, NH-alkyl, N(alkyl)2, NO2 or R2 and R3 together may form -CH=CH-CH=CH-; G1 represents bicyclic or tricyclic condensed azepine derivatives selected from general formulae 3-8 wherein A1, A4, A7, and A10 are independently CH3, O, and NR5; A2, A3, A9, A11, A12, A14, and A15 are independently CH and N; or A5 represents covalent bond and A6 represents S; or A5 represents N=CN and A6 represents covalent bond; A8 and A12 are independently NH, N-CH3 and S; A16 and A17 both represent CH2 or one of A16 and A17 represents CH2 and the other represents CH(OH), CF2, O, SOa, and NR5; R5 represents H, alkyl, CO-alkyl, and (CH2)bR6; R6 represents phenyl, pyridyl, OH, CO2H; a = 0-2; b = 1-4; Y represents CH or N; Z represents CH=CH or S; and G2 represents group selected from groups of formulae 9-11 wherein Ar represents phenyl, pyridyl, naphthyl, and mono- or polysubstituted phenyl, pyridyl, wherein substituents are selected from F, Cl, Br, alkyl, NO2; D represents covalent bond or NH; E1 and E2 both are H, OMe, F, or one of E1 and E2 represents OH, O-alkyl, OBn, OPh, OAc, F, Cl, Br, N2, NH2, NHBn or NHAc and the other represents H; or E1 and E2 together form =O, -O(CH2)gO- or -S(CN2)gS-; F1 and F2 both represent H or together form =O or =R; L represents OH, O-alkyl, NH2, NH-alkyl, and NR9R10; R7 represents COR8; R8 represents OH, O-alkyl, NH2, NH-alkyl, N(alkyl)2, pyrolidinyl, and piperidinyl; R9 and R10 both are alkyl or together form -(CH2)h-; V represents O, N-CN or S; c = 0 or 1; d = 0 or 1, e = 0 or 1; f = 0-4; g = 2 or 3; h = 3-5, with the proviso, that both d and e are not 0. Also disclosed are pharmaceutical composition having agonistic activity in relate to V2 receptor, method for treatment one or more diseases (e.g., enuresis, nycturia, diabetes insipidus, hemorrhage disorders, urinary incontinence.

EFFECT: new compounds with value biological characteristics.

41 cl, 19 tbl, 193 ex

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

SUBSTANCE: invention describes bicyclic N-acylated imidazo-3-amines or imidazo-5-amines salts of the general formula (I): wherein R1 means tert.-butyl, 1,1,3,3-tetramethylbutyl, (C4-C8)-cycloalkyl, phenyl disubstituted with (C1-C4)-alkyl, -CH2Ra wherein Ra means the group -CO(OR') wherein R' means (C1-C8)-alkyl; R2 means hydrogen atom, the group -CORb wherein Rb means (C1-C8)-alkyl or (C3-C8)-cycloalkyl; R3 means (C1-C8)-alkyl, (C3-C8)-cycloalkyl, phenyl, pyridyl, furfuryl or thiophenyl; A means tri-linked fragment of ring of the formula: wherein R6 and R7 mean hydrogen atom or tetra-linked fragment of ring of the following formulae: wherein R4' means hydrogen atom or benzyloxy-group; R5' means hydrogen atom; R6' means hydrogen atom, (C1-C8)-alkyl or nitro- (NO2)-group; R7' means hydrogen atom, (C1-C8)-alkyl, or R6' and R7' mean in common the following fragment of ring: -CRi=CRj-CH=CH- wherein Ri and Rj mean hydrogen atom; R5'' means hydrogen, chlorine atom or (C1-C8)-alkyl; R6'' means hydrogen atom; R7''n means hydrogen atom, amino- (NH2)-group or (C1-C8)-alkyl; R4''', R6''' and R7''' mean hydrogen atom; R8 means (C1-C8)-alkyl or (C3-C8)-cycloalkyl; X means anion of inorganic or organic acid, or their acid-additive compounds. Also, invention relates to a method for their preparing and a pharmaceutical composition based on thereof. These new compounds show affinity to opiate μ-receptor and can be used, in particular, as analgesic agents.

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

12 cl, 2 dwg, 32 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention describes new 7-azaindoles of the general formula (I): wherein n = 1 or 2; R1 means mono- or multi-unsaturated, linear or branched (C2-C10)-alkenyl, linear or branched, unsubstituted (C1-C10)-alkyl that can be monosubstituted with (C1-C6)-alkoxy-group, naphthyl, pyridinyl, (C3-C6)-cycloalkyl, phenyl that, in turn, can be substituted with (C1-C6)-alkyl, halogen atom, (C1-C6)-alkoxy-group or hydroxy-group, or radical of the formula: ; R2 and R3 are similar or different being only one of them can mean hydrogen atom and mean (C1-C5)-alkyl possibly substituted with -O-(C1-C6)-alkyl or pyridyl, phenyl possibly substituted twice with -F, -Cl, -Br, -O-(C1-C3)-alkyl or monosubstituted with -COOH or -COO-(C1-C3)-alkyl, pyridyl possibly twice substituted with -Cl, -Br, or group of formulae: or , or R2 and R3 in common with N-atom mean: or under condition that if n = 1 then they don't mean simultaneously: R1 - (C1-C6)-alkyl; R2 - hydrogen atom (H) or (C1-C6)-alkyl, and R3 or wherein R and R' mean independently -Cl or -Br. These compounds possess inhibitory activity with respect to activity of phosphodiesterase 4. Also, invention relates to a medicinal agent comprising these compounds, methods for its preparing and using these compounds for preparing medicinal agents.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and drug.

17 cl, 6 tbl, 40 ex

FIELD: organic chemistry, medicine, pharmacology, pharmacy.

SUBSTANCE: invention relates to a new physiologically active composition effecting on nicotine receptors and prepared in the form of tablets, granules, capsules, suspensions, solutions and injections. As an active component the composition comprises pharmaceutically effective amount of substituted 1-oxo-1,2-dihydro[2,7]-naphthyridine of the general formula (1)

or its salt, N-oxide or hydrate wherein R1 represents hydrogen atom, inert substitute, optionally substituted (C1-C5)-alkyl, optionally substituted amino-group; R2 and R3 represent independently of one another hydrogen atom, nitrile group, formyl group, inert substitute, optionally substituted (C1-C5)-alkyl, carboxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group or optionally substituted carbamoyl group; R4 at carbon atoms of pyridine moiety represents: hydrogen atom, halogen atom, inert substitute, optionally substituted hydroxy-(C1-C5)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group, optionally substituted carbamoyl group; R4 at nitrogen atom of pyridine moiety forms pyridinium salt with pharmacologically acceptable anion and represents inert substitute. Also, invention relates to new substituted 1-oxo-1,2-dihydro[2,7]naphthyridines of the general formula (1) or their salts, N-oxides or hydrates wherein R1 and R4 have value given in cl. 1, and R2 and R3 represent independently of one another carboxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group or optionally substituted carbamoyl group. Also, invention relates to a method for their preparing and to a method for modulating activity of nicotine receptor and using compounds of the general formula (1) by cl. 1 for preparing physiologically active composition, and as ligands of nicotine receptors for aims of experimental investigations of physiological processes as "pharmacological tools". Also, invention relates to a set for preparing the composition.

EFFECT: improved preparing method, valuable properties of compounds and compositions.

7 cl, 2 sch, 2 tbl, 5 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention describes a compound of the general formula (I) or (II) wherein R1 represents hydrogen atom; R2 is taken among the group consisting of aryl and heteroaryl; R3 is taken among the group consisting of halogen atom, nitro-, cyano-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, trifluoromethyl, trifluoromethoxy-group, -NH2, -NH-(C1-C6)-alkyl and -N-(C1-C6)-alkyl)2; b is a whole number from 0 to 4; R4 is taken independently among the group consisting of halogen atom, hydroxy-, carboxy-, oxo-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C1-C6)-alkoxycarbonyl, phenyl (wherein phenyl group can be substituted optionally with one-three substitutes taken independently among RD), phenylsulfonyl, heteroaryl (wherein heteroaryl can be substituted optionally with one-three substitutes taken independently among RD), heterocycloalkyl, -NH2, -NHRA, -N-(RA)2,

wherein each RD is taken independently among halogen atom, hydroxy-, carboxy-, oxo-group, (C1-C4)-alkyl, (C1-C4)-alkylthio, hydroxy-(C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylcarbonyl, trifluoromethyl, trifluoromethoxy-group, -NH2. -NHRA, -N-(RA)2, -C(O)N(RA)2, -SO2N(RA)2, acetylamino-, nitro-, cyano-group, formyl, (C1-C6)-alkylsulfonyl, carboxy-(C1-C6)-alkyl and aralkyl; c = 0; a means a whole number from 0 to 1; Y is taken among the group consisting of a residue -(C1-C)-alkyl, -C(O)-, -(C2-C6)-alkenyl)-carbonyl, -carbonyl-(C1-C6)-alkyl)-, -C(S)-, -C(O)NH-(C1-C6)_alkyl), -C(O)-(C3-C7)-cycloalkyl)- and (C3-C7)-cycloalkyl)-C(O)-; represents phenyl;

is taken among the group consisting of phenyl, heteroaryl and cycloalkyl under condition that when R1 represents hydrogen atom, R3 represents hydrogen atom, b = 0, c = 1, Y represents -CH2-, represents phenyl and represents phenyl then R2 is not trimethoxyphenyl, and its pharmaceutically acceptable salts. Also, invention describes a pharmaceutical composition designated for inhibition of activity of phosphodiesterase comprising a pharmaceutically acceptable vehicle and compound by cl. 1, method for preparing pharmaceutical composition, methods for treatment of sexual dysfunction by using compound by cl. 1 or pharmaceutical composition, method for increasing the concentration of cGMP in penis tissue and method for treatment of state when inhibition of activity of phosphodiesterase shows the favorable effect. Invention provides preparing novel compounds possessing useful biological properties.

EFFECT: valuable medicinal and biochemical properties of compounds and composition.

17 cl, 7 tbl, 98 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new urea-substituted imidazoquinolines of the formula (1):

wherein R, R1, R2 and n have values given in the description, and to pharmaceutical preparations based on these compounds. Proposed compounds possess effect of immunomodulators initiating biosynthesis of different cytokines. Also, invention relates to methods for treatment of different states, among them viral diseases and neoplastic pathologies.

EFFECT: improved method for induction, valuable properties of compounds.

47 cl, 11 tbl, 142 ex

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention describes derivatives of imidazo-3-ylamine of the general formula (I):

wherein X and Y mean CH or nitrogen atom (N) under condition that X and Y don't mean nitrogen atom (N) simultaneously; R1 means tert.-butyl, (CH2)nCN wherein n means 4, 5 or 6, phenyl substituted optionally with (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C4-C8)-cycloalkyl, 1,1,3,3-tetramethylbutyl or CH2Ra wherein Ra represents hydrogen atom, branched or linear (C1-C8)-alkyl, phenyl substituted optionally with halogen atom, (C1-C4)-alkoxy-group, CO(OR') wherein R' means linear (C1-C4)-alkyl or branched (C3-C5)-alkyl, PO(OR')2 wherein R' means linear (C1-C4)-alkyl or branched (C3-C5)-alkyl; R2 means hydrogen atom, CORb wherein Rb represents branched or linear (C1-C4)-alkyl; R3 means methyl, ethyl, tert.-butyl, (C3-C8)-cycloalkyl, phenyl monosubstituted optionally at position 3, 5 or 6 or optionally multisubstituted at position 4 and additionally at position 2 and/or 3, and/or 5, and/or 6 with halogen atom, hydroxyl group (OH), (C1-C4)-alkyl or (C1-C4)-alkoxy-group, naphthyl, optionally substituted (C1-C4)-alkoxy-group, di-(C1-C4)-alkylamino-group, pyrrole substituted optionally with (C1-C4)-alkyl, benzylsulfonyl, COOCH3, pyridyl substituted optionally with (C1-C4)-alkyl, OH, hydroxy-(C1-C4)-alkyl, furan substituted optionally with (C1-C4)-alkyl, nitro-group (-NO2), halogen-substituted phenyl, CH2COOCH3, COOH, thiophene substituted optionally with halogen atom, (C1-C4)-alkyl, (C1-C4)alkylsulfanyl, -NO2, phenoxy-group, thiophene, alkynylphenyl, unsubstituted anthracene or quinoline substituted optionally with halogen atom under condition that R3 doesn't means cyclohexyl-unsubstituted phenyl or phenyl monosubstituted with carboxylic acid amide at position 3 if R1 means tert.-butyl, n-propyl, n-butyl, 1,1,3,3-tetramethylbutyl, cyclohexyl, monosubstituted phenyl, 2,6-dimethylphenyl or benzyl, and R2 means simultaneously hydrogen atom or -CO-(methyl) and under condition that R2 doesn't mean hydrogen atom if R1 means benzyl simultaneously and R3 means methyl or R1 means simultaneously CH2C(O)-tert.-butyl and R3 means unsubstituted phenyl, in forms of bases or pharmaceutically acceptable salts, and a method for their preparing and a medicinal agent based on thereof. Described compounds possess analgesic activity and can be used in medicine.

EFFECT: improved preparing method, valuable medicinal properties of compounds and agent.

7 cl, 2 tbl, 33 ex

FIELD: organic chemistry, antibacterial agents.

SUBSTANCE: invention describes 8-cyano-1-cyclopropyl-7-(1S,6S)-2,8-diazabicyclo-[4.3.0]-nonane-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid of the formula (I): with the crystalline modification A and a drug eliciting effect against pathogenic microorganisms. The prepared crystalline modification shows stability and doesn't transform to another crystalline modification or amorphous form being even at prolonged storage.

EFFECT: improved and valuable properties of compound.

4 cl, 4 dwg, 6 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes 8-cyano-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]-nonane-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid of the formula (I):

in the crystalline modification B and a medicinal agent based on thereof that elicits effect against pathogenic microorganisms. Indicated modification of compound of the formula (I) shows stability and insignificant absorption of air moisture ant doesn't convert to another crystalline modification or amorphous form being even in the prolonged storage.

EFFECT: valuable properties of agent.

4 cl, 4 dwg, 6 ex

FIELD: organic chemistry, medicine pharmacy.

SUBSTANCE: invention describes 8-cyano-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]-nonane8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid in the crystalline modification C of the formula (I):

and a medicinal agent eliciting effect against pathogenic microorganisms. This crystalline modification of compound of the formula (I) elicits low hygroscopicity, satisfied friability and can be processed easily to galenic preparations.

EFFECT: valuable properties of agent.

4 cl, 7 dwg, 1 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes 8-cyclo-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]-nonane-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid of the formula (I):

in crystalline modification D and a medicinal agent based on thereof eliciting effect against pathogenic microorganisms. The prepared crystalline form of compound of the formula (I) shows low hygroscopicity and can be processed to galenic preparations easily and it has the highest filled density and satisfied fluidity.

EFFECT: valuable properties of agent.

4 cl, 7 dwg, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new imidazoquinolines of the formula (1): wherein R, R1, R2 and n have values given in the description. Compounds elicit effect of immunomodulating agents inducing biosynthesis of cytokines in animals in treatment of different pathologies, among them viral and neoplastic diseases. Also, invention relates to a pharmaceutical preparation used for inducing interferon-α or tumor necrosis α-factor, to a method for inducing biosynthesis of cytokines in animals and to methods for treatment of viral diseases and neoplasm pathologies in animals. Invention provides preparing new biologically active compounds.

EFFECT: improved inducing method, valuable properties of compounds and pharmaceutical preparation.

23 cl, 10 tbl, 231 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes compound of the formula (I): wherein cycle A represents imidazo[1,2-a]pyrid-3-yl or pyrazole[2,3-a]pyrid-3-yl; R2 is joined to cyclic carbon atom and taken among halogen atom, cyano-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C1-C6)-alkyl-S(O)a wherein a = 0, phenyl, phenylthio- or (heterocyclic group)-thio-group wherein any (C1-C6)-alkyl, phenyl or heterocyclic group can be substituted optionally by carbon atom with one or some G wherein heterocyclic group represents saturated, partially saturate or unsaturated, mono- or bicyclic structure comprising 4-12 atoms among them at least atom is taken among nitrogen, sulfur or oxygen atom that can be bound if another variants are not specified with unsaturated, mono- or bicyclic structure comprising 4-12 atoms among them at least one atom is taken among nitrogen, sulfur or oxygen atoms that can be bound if another variants are not specified with carbon or nitrogen atom wherein group -CH2- can be substituted optionally with -C(O)- and cyclic atom can carry optionally (C1-C6)-alkyl group and to form quaternary compound, or cyclic atom of nitrogen and/or sulfur can be oxidized to form N-oxide and/or S-oxides; m = 0-2 and R2 values can be similar or different; R1 means halogen atom, (C1-C3)-alkyl-S(O)a wherein a = 0 wherein any (C1-C3)-alkyl can be substituted optionally by carbon atom with one or some J; n = 0-1; cycle B represents phenyl or phenyl condensed with (C5-C7)-cycloalkyl cycle; R3 means halogen atom or sulfamoyl; p = 0-2 and R3 values can be similar or different; R4 means group A-E- wherein A is taken among (C1-C6)-alkyl, phenyl, heterocyclic group, (C3-C8)-cycloalkyl, phenyl-(C1-C6)-alkyl, (heterocyclic group)-(C1-C6)-alkyl or (C3-C8)-cycloalkyl-(C1-C6)-alkyl wherein (C1-C6)-alkyl, phenyl, heterocyclic group, (C3-C8)-cycloalkyl, phenyl-(C1-C6)-alkyl, (heteroccyclic group)-(C1-C6)-alkyl or (C3-C8)-cycloalkyl-(C1-C6)-alkyl can be substituted optionally by carbon atom with one or some D and wherein above mentioned heterocyclic group comprises fragment -NH- then nitrogen atom can be substituted optionally with group taken among R; E means a simple bond or -O-, -C(O)-, -N(Ra)C(O)- or -N(Ra)SO2-, -S(O)r wherein Ra means hydrogen atom or (C1-C6)-alkyl and r = 0-2; D is taken independently among hydroxy-, amino- (C1-C6)-alkoxy-, N-(C1-C6-alkyl)-amino-, N,N-(C1-C6-alkyl)-amino-, (C1-C6)-alkoxycarbonylamino- and benzyloxycarbonylamino-group wherein any (C1-C6)-alkyl or phenyl can be substituted optionally by carbon atom with one or some K; q = 0-1; G, J and K are taken independently among hydroxy-, dimethylamino-, diethylamino-group; R is taken among (C1-C4)-alkyl; or its pharmaceutically acceptable salt. Invention proposes applying pyrimidine compounds for inhibition of activity of kinases CDK2, CDK4 and CDK6 in cellular cycle eliciting anti-proliferative properties. Indicated properties have value in treatment of cancer diseases (solid tumors and leukemia), fibroproliferative and differential disorders, psoriasis, rheumatoid arthritis, Kaposi's sarcoma, hemangioma, acute and chronic nephropathy, atheroma, atherosclerosis, arterial repeated stenosis, osseous and ophthalmic diseases with proliferation of cellular tissue in vessels.

EFFECT: valuable medicinal properties of compounds.

22 cl, 99 ex

FIELD: organic chemistry, madicine.

SUBSTANCE: tricyclic benzodiazepines of formula I as well as their pharmaceutical acceptable salts, pharmaceutical composition containing the same and methods for hypertension treatment are disclosed. In formula A is -C(O)-; Y is CH2 or CH as olefinic site; X is CH2 or CH as olefinic site S, O or NR3 (R3 is C1-C8-alkyl) with the proviso that when Y is CH, X also is CH; Z is N or CH; R1 is hydrogen, C1-C8-alkyl, C1-C8-alkoxy or halogen; R2 is NR4COAr (R4 is hydrogen; Ar is phenyl optionally substituted with 1-3 substitutes independently selected from C1-C8-alkyl, halogen, hydroxyl, fluorinated C1-C8-alkylthio and another phenyl optionally substituted with substitute selected from C1-C4-alkyl, halogen, and hydroxyl); R5 is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, fluorine, chlorine, hydroxyl or di-(C1-C4)-alkylamino.

EFFECT: improved pharmaceutical composition for hypertension treatment.

12 cl, 5 tbl, 52 ex

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

SUBSTANCE: invention relates to a new improved method for preparing 6-methyl-2-(4-methylphenyl)-imidazolo[1,2-a]pyridine-3-(N,N-dimethylacetamide) of the formula (I) or its pharmaceutically acceptable acid additive salts. Method involves interaction of ester of the general formula (II) (wherein R is a lower alkyl or phenyl-lower alkyl) with dimethylamine in polar aproton solvent and if necessary conversion of synthesized compound of the formula (I) to pharmaceutically acceptable acid additive salt. Compound of the formula (I) is the known effective sedative agent used in therapy. Also, invention relates to intermediate compounds of the general formula (II) wherein R is a lower alkyl or phenyl-lower alkyl using in this method. Method provides preparing highly pure product for a single stage being without applying harmful and toxic reagents.

EFFECT: improved method for preparing.

16 cl, 15 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyclic amide of the formula (I)

or its salt, or hydrate, or solvate wherein X represents (C1-C6)-alkyl, (C1-C6)-alkyl substituted with phenyl, (C2-C6)-alkenyl substituted with phenyl or halogenphenyl, (C2-C6)-alkynyl substituted with phenyl, phenyl that can be substituted with (C1-C6)-alkyl; one or more halogen atom, nitro-group, phenyl, (C1-C6)-alkoxy-group, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy-group, phenyl-(C1-C6)-alkyl, (C1-C6)-alkoxyphenyl-(C1-C6)-alkyl, amino-group, optionally substituted with (C1-C6)-alkyl, acetyl, (C1-C6)-alkoxy-group, substituted with phenyl, phenylcarbonyl, furanyl; 1- or 2-naphthyl, monocyclic (C3-C8)-cycloalkyl, amino-group substituted with one or more substitutes taken among phenyl, halogenphenyl, (C1-C6)-alkoxyphenyl, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, phenyl-(C1-C6)-alkyl; 5- or 6-membered monocyclic heterocyclic group comprising 1 or 2 heteroatoms, such as nitrogen (N), oxygen (O), sulfur (S) atom optionally substituted with halogenphenyl, halogen atom, benzyl, (C1-C6)-alkyl, phenyl; 8-10-membered bicyclic heteroaryl group comprising 1 or 2 heteroatoms taken among N, O and optionally substituted with halogen atom; 8-10-membered polycyclic cycloalkyl group; Q means -CH2-, -CO-, -O-, -S-, -CH(OR7)- or -C(=NR8)- wherein R7 means hydrogen atom (H), (C1-C6)-alkyl; R8 means OH, (C1-C)-alkoxy-group, acylamino-group, (C1-C6)-alkoxycarbonylamino-group, phenyl-(C1-C6)-alkoxy-group; n = 0-5; B represents group or wherein each among R3, R4, R5 and R6 represents independently substitute taken among group consisting of hydrogen atom (H), halogen atom, NO2 (nitro-group), (C1-C6)-alkoxy-group, CN (cyano-group); m = 1 or 2; ring represents 5- or 6-membered aromatic heterocyclic ring comprising one or two heteroatoms taken among O, S, N. Compound of the formula (I) elicit activity inhibiting binding sigma-receptors that allows their using as component of medicinal agent.

EFFECT: valuable medicinal properties of compounds.

21 cl, 2 sch, 4 tbl, 183 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new substituted 1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines of the general formula (1)

that are effective inhibitors if caspase-3 that can be used for preparing medicinal agents and for experimental (in vitro, in vivo) investigation of apoptosis processes as "pharmacological tools". Also, invention proposes pharmaceutical composition and a method for their preparing and applying. In the general formula (1) radicals R1, R2, R3 and R8 represent independently of one another hydrogen atom, halogen atom, CF3, CN, inert substitute, optionally substituted hydroxyl group, optionally substituted carboxy-(C1-C6)-alkyl group, optionally substituted carbamoyl group; R4 represents hydrogen atom, halogen atom, inert substitute, optionally substituted amino-group, substituted hydroxyl group; R5 represents hydrogen atom, inert substitute, optionally substituted hydroxy-(C1-C5)-alkyl, optionally substituted amino-(C1-C7)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group; R6 and R7 represent independently of one another hydrogen atom, inert substitute, optionally substituted amino-(C1-C7)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group; or R6 and R7 in common with nitrogen atom to which they are bound represent optionally substituted and optionally additionally including heteroatom taken among group: oxygen, nitrogen or sulfur, 3-10-membered cycle; or R6 and R7 in common with nitrogen atom to which they are bound represent condensed heterocycle being optionally substituted and optionally additionally including heteroatom taken among group: oxygen, nitrogen or sulfur.

EFFECT: improved preparing method and treatment.

9 cl, 19 sch, 7 tbl, 25 ex

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