Novel 2-azetidinone derivatives as cholesterol absorption inhibitors for treating hyperlipidemic conditions

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I): where: X denotes CH2-, -CH2CH2- ; Y denotes -CH2- or O; Y1 denotes -CH2- or O; where at least on of Y and Y1 denote -CH2-; R1 denotes H; R2 and R3 independently denote hydrogen; or one of them denotes H2 and the other denotes a branched or straight C1-6alkyl; where the said C1-6alkyl is possibly substituted with one amino, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C3-6cycloalkyl, phenyl; where any phenyl is possibly substituted with one CN; R4 denotes H; R5 denotes halogen; or its pharmaceutically acceptable salt.

EFFECT: compounds inhibit cholesterol absorption, which enables their use in treating and preventing atherosclerosis.

12 cl, 15 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):

(I)
where X represents CH2- or-CH2CH2-;
Y represents-CH2- or;
Y1represents-CH2- or;
where at least one of Y and Y1represents-CH2-;
R1represents H;
R2and R3independently represent hydrogen; or one of R2and R3represents hydrogen and the other represents a branched or unbranched1-6alkyl; where the specified C1-6the alkyl can be substituted with one amino, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C3-6cycloalkyl or phenyl; and where any phenyl group may be substituted by one cyano;
R4represents hydrogen;
R5selected from halogeno; or its pharmaceutically acceptable salt.

2. The compound according to claim 1, which represents a compound of formula (I2):

where X represents-CH2- or-CH2CH2-;
Y represents-CH2- or;
Y1represents-CH2- or;
where at least one of Y and Y1represents-CH2-;
R1represents H;
R2and R3ezavisimo represent hydrogen; or one of R2and R3represents hydrogen and the other represents a branched or unbranched C1-6alkyl; where specified With1-6the alkyl can be substituted with one amino, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C3-6cycloalkyl or phenyl; and where any phenyl group may be substituted by one cyano;
R4represents hydrogen;
R5selected from halogeno; or its pharmaceutically acceptable salt.

3. The compound according to claim 1 or 2, where X represents-CH2-.

4. The compound according to claim 1 or 2, where X represents-CH2CH2-.

5. The compound according to claim 1 or 2,
where R1represents hydrogen;
R2and R3represent hydrogen or one of R2and R3represents hydrogen and the other represents or branched or non-branched C1-6alkyl; where the specified C1-6alkyl substituted With3-6cycloalkyl, phenyl or amino;
R4represents hydrogen.

6. The compound according to claim 1 or 2,
where R1represents hydrogen;
R2and R3represent hydrogen; or one of R2and R3represents hydrogen and the other represents a branched or unbranched C1-6alkyl; where specified With1-6alkyl samisens 3-6cycloalkyl;
R4represents hydrogen.

7. The connection according to claim 6, where
R2represents hydrogen, and R3represents tert-butyl.

8. The connection according to claim 6,
where R2represents hydrogen, and R3represents methyl; where specified methyl substituted cyclohexyl.

9. The compound according to claim 1 or 2,
where R5selected from chlorine or fluorine.

10. One or more than one compound according to claim 2, selected from:
N-({4-[(2R,3R)-3-{[2-(2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-D-lysine;
N-({4-[(2R,3R)-3-{[2-(2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-b,b-dimethyl-D-phenylalanine; and
N-({4-[(2R,3R)-3-{[(2R or S)-2-(2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-cyclohexyl-D-alanine of ammoniate;
N-({4-[(2R,3R)-3-{[(2R or S)-2-(2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-methyl-D-valine;
N-{{4-[(2R,3R)-3-{[(2R or S)-2-(2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-D-valine;
N-({4-[(2R,3R)-3-{[{2R or S)-2-(2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-4-cyano-D-phenylalanine;
N-({4-[(2R,3R)-3-{[2-(2,3-Digi the ro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-N 6N6-dimethyl-L-lysine;
N-({4-[(2R,3R)-3-{[(2R or 3)-2-(2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-methyl-D-isovaline;
N-({4-[(2R,3R)-3-{[2-(2,3-dihydro-1-benzofuran-5-yl)-2-hydroxyethyl]thio}-1-(4-forfinal)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycylglycine.

11. A method of treating or preventing atherosclerosis, comprising introducing an effective amount of a compound according to any one of claims 1 to 10 to a mammal in need of it.

12. The pharmaceutical composition inhibiting the absorption of cholesterol containing compound according to any one of claims 1 to 10 in a mixture with pharmaceutically acceptable adjuvants, diluents and/or carriers.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds of formula (Ia) or their pharmaceutically acceptable salts, tautomers, or N-oxides, for use in prevention or treatment of unhealthy conditions or diseases, mediated with cyclin-dependent kinase and glycogen synthase-kinase-3, such as cancerous diseases. In formula (Ia) X stands for group R1-A-NR4; A stands for link, C=O, or NRg(C=O, where R8 stands for hydrogen or C1-3 alkyl; Y stands for link or alkylene chain, made of 1, 2 or 3 atoms of carbon; R1 stands for carbocyclic or heterocyclic group, containing from 3 to 12 circular units; or saturated C1-8hydrocarbyl group, optionally substituted with one or more substituents selected from halogen (for instance, fluorine), hydroxygroups, C1.4alkoxygroups, and carbocyclic or heterocyclic groups, and where 1 or 2 atoms of hydrocarbyl group carbon may be optionally substituted with atom or group selected from O, S, NH, SO, SO2; R2 stands for hydrogen or methyl; R3 is selected from hydrogen and carbocyclic or heterocyclic groups, containing from 3 to 6 circular units; and R4 stands for hydrogen or methyl. Specified carbocyclic and heterocyclic groups are determined in formula of invention and may be optionally substituted with groups specified in invention formula. Objects of invention are also a pharmaceutical composition based on proposed compounds, their application to produce medicinal agents and methods of their application.

EFFECT: production of pharmaceutical composition based on proposed compounds for use in prevention or treatment of unhealthy conditions or diseases, mediated with cyclin-dependent kinase and glycogen synthase-kinase-3, such as cancerous diseases.

48 cl, 6 tbl, 254 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula I:

, where: U, V and W independently represent CR5 where R5 stands for H, C1-C6alkyl; Q stands for NR5, NNR5, NO, CR5, where R5 stands for H, C1-C6alkyl; L1 stands for -NR5C(O)-, -NR5C(O)NR5-, -C(O)NR5-, -NR5- and C5heteroaryl, containing 2 N atoms and 1 O atom, where R5 stands for H, C1-C6alkyl; L2 represents bond, -O-, -NR5C(O)-, -NR5C(O)NR5-, -C(O)NR5- ,-NR5-, where R5 stands for H, C1-C6alkyl; n = 0 or 1; m = 0, 1, 2, 3 or 4; R1 stands for C6-C10aryl and C5heteroaryl, containing 1 N atom, condensed with benzene; where any aryl, heteroaryl, contained in R1, can be optionally substituted with 1-3 radicals, which represent halogen, NH2, NO2, CN, C1-C6alkyl, C1-C6alkoxygroup, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup, C6-C10aryl-C0-C4alkyl, C5-C6heteroaryl-C0-C4alkyl, containing 1 or 2 N, C5-C6heterocycloalkyl-C0-C4alkyl, containing 1 or 2 N and/or O atoms; where methylene fragment of any alkyl group can be optionally substituted with O; where any aryl, heteroaryl or heterocycloalkyl substituent, contained in R1, can be optionally substituted with 1-3 radicals, which independently represent C1-C6alkyl, C1-C6alkoxygroup, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup and hydroxy-substituted C1-C6alkyl; R2 represents halogen, NH2, NO2, CN, C1-C6alkyl, C1-C6alkoxygroup, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup, C6-C10aryl-C0-C4alkyl, C5heteroaryl-C0-C4alkyl, containing 1 or 2 N, C6heterocycloalkyl-C0-C4alkyl, containing 1 or 2 N atoms and/or O; where any aryl, heteroaryl or heterocycloalkyl, contained in R2, is optionally substituted with 1-3 radicals, which independently represent halogen, NH2, NO2, CN, C1-C6alkyl, C1-C6alkoxygroup, halogen-substituted C1-C6alkyl and halogen-substituted C1-C6alkoxygroup; R3 represents H, C1-C6alkyl; R4 represents H, -XR6, -XNR5XR6, -XOXR6 and -XNR5XNR5R6; where each X independently represents bond and C1-C4alkylene; where any alkylene, contained in X can be optionally substituted with OH; R5 represents H, C1-C6alkyl; R6 represents C6-C10aryl and C5heteroaryl, containing 1 or 2 N and/or O, optionally condensed with benzene; where any aryl, heteroaryl, contained in R6, can be optionally substituted with 1-3 radicals, which independently represent C1-C6alkyl, OH, CN, -NR5S(O)0-2R5, -S(O)0-2NR5R5, - NR5S(O)0-2NR5R5, -C(O)NR5XNR5R5, -XNR5XNR5R5, -C(O)R7, -C(O)NR5XOR5, -C(O)NR5R5, -C(O)NR5R7, -C(O)NR5XR7 and -XC(O)OR5; where each X independently represent bond and C1-C4alkylene; where any alkylene, contained in X, is optionally substituted with OH; where each; R5 represents H, C1-C6alkyl; R7 represents C5-C6heterocycloalkyl-C0-C4alkyl, containing 1 or 2 N and/or O, where any heterocycloalkyl, contained in R7, is optionally substituted with radical, which represents diethylaminoethyl, dimethylaminogroup, aminogroup, C1-C6alkyl, pyrimidinyl, pyrazinyl, halogen-substituted C1-C6alkyl and -C(O)OR5; and its pharmaceutically acceptable salts, hydrates, solvates.

EFFECT: compounds possess inhibiting activity with respect to series of kinases, which allows to use them in pharmaceutical composition.

10 cl, 1 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to derivatives of 2-pyridylmethylenecarboxamide of formula (I), where: -A represents a substituted or unsubstituted 5-member heterocyclyl group bound with carbonyl through carbon atom; -Z1 and Z2 which can be equal or different, represent hydrogen atom; C1-C5-alkyl; C5-alkoxycarbonyl; -Z3 represents substituted or unsubstituted C3-C7cycloalkyl; -Y represents C1-C5-halogenalkyl, containing to 5 halogen atoms which can be equal or different; X which can be equal or different, represents halogen atom, - n=0, 1, 2 or 3; and to their salts. Besides the invention describes a method of plant pathogenic fungi control with the use of such compounds.

EFFECT: there are prepared and described new derivatives of 2-pyridylmethylenecarboxamide which can be effective as fungicidal active agents.

8 cl, 96 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: invention refers to new compounds exhibiting antiproliferative activity of formula (1) where W means N or C-R2; X means -NH-; Y means CH; Z means halogen, -NO2, C2-C3alkynyl-, halogen-C1-C3alkyl- and -C(=O)-C1-C3alkyl, A means a group of formula (i), (ii) or (iii) Q1 means phenyl; B1, B2, B3 and B4 independently mean C-RgRh, N-Ri or O; R1 means hydrogen; R2 means a residue specified from the group including hydrogen, halogen and -OR4; Ra, Rb, Rc, Rd, Re and Rf independently mean hydrogen; Rg and Rh independently mean a residue specified from the group including hydrogen, =O, -OR4 and -NR4C(=O)R5; or mean optionally a residue monosubstituted or twice-substituted with equal or different substitutes and specified from the group including C1-C6alkyl and phenyl, the substitute/substitutes is/are specified from the group including R8/, -OR4, -C(=O)R4, -C(=O)OR4 and -C(=O)NR4R5 where R8/ and other values of radicals are specified in the patent claim, optionally in the form of their pharmacologically noncontaminating acid addition salts. The invention also concerns a pharmaceutical composition.

EFFECT: new compounds have effective biological properties.

8 cl, 6 dwg, 1086 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of 2,4-di(hetero)arylaminopyrimidine of general formula I or its pharmaceutically acceptable salt, possessing properties of ZAP-70 inhibitors. In compounds of formula I: Z stands for =CR2-; each of radicals R0 and R1 represents hydrogen; R2 represents (C1-C4)alkoxy; R3 represents -SO2NH2; or R1 and R2 form together with C-atoms, to which they are bound, 5-7-member non-aromatic carbocyclic or heterocyclic residue, where said heterocyclic residue includes 1 or 2 heteroatoms, selected from N and O, and heterocyclic residue, containing 1-2 atoms of oxygen can be substituted with fluorine atoms; R4 and R6 represent hydrogen, R5 represents hudrogen, halogen, (C1-C4)alkyl or CF3; one of R7, R8 and R9 represents NR10R11, and one or two others represent hydrogen, halogen, COOH, CF3 or (C1-C4)alkyl; R10 and R11 independently represents hydrogen or (C1-C4)alkyl. Invention also relates to methods of obtaining compounds.

EFFECT: compounds can be applied, for instance in case of acute or chronic rejection of organ or tissue, in treatment of atherosclerosis and other diseases, when inhibition of ZAP-70 is of importance.

9 cl, 7 tbl, 150 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which possess properties inhibiting HIV replication, of general formula (I) , in form of E-isomer, in which -a1=a2-a3=a4- represents bivalent radical of formula -CH=CH-CH=CH- (a-1); -b1=b2-b3=b4. Represents bivalent radical of formula -CH=CH-CH=CH- (b-1); n equals 0; m equals 2; each of R1 radicals independently on each other stands for hydrogen atom; C1-6alkyl; R2a stands for cyanogroup; X1 stands for -NR1-; R3 represents C2-6alkenyl, substituted with cyanogroup; R4 stands for C1-6alkyl; R5 represents radical of formula -Y-Alk-L, -Alk'-Y-L or -Alk'-Y-Alk-L; each of radicals Alk or Alk' independently represents bivalent C1-6alkyl or C2-6 alkenyl group; L stands for aryl or Het; Y stands for NR1; -CH=N-O-; Het stands for 5- or 6-member fully saturated ring system, in which one, two or three ring elements represent heteroatoms, each of which is independently selected from group, including nitrogen, oxygen and sulphur, and in which other ring elements represent carbon atoms; and, if possible, any nitrogen ring element can be optionally substituted with C1-6alkyl; and ring system can be optionally bound with benzene ring; and in which any carbon atom of ring, including any carbon atom of optionally bound benzene ring, each independently can be substituted with substituent selected from such groups as halogen atom, C1-6alkyl, hydroxyC1-4alkyl, carboxyC1-4alkyl, C1-4 alkylcarbonyloxyC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, aryloxy, morpholinyl, aryl, Het1; Het1 stands for thienyl, isoxazolyl, thiadiazolyl, each of which can be optionally substituted with one or two C1-4alkyl radicals; Q stands for hydrogen atom; each aryl represents phenyl or phenyl, substituted with one, two substituents, each of which is independently selected from such groups as halogen atom, C1-6alkyl, C2-6alkinyl, cyano, polyhalogen C1-6alkyl or Het1, as well as to its pharmaceutically acceptable additive salts Invention also relates to pharmaceutical composition.

EFFECT: creation of novel compounds, which possess properties inhibiting HIV replication

5 cl, 7 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline, represented by formula , where R1 represents (1-6C)alkyl; R2 represents halogen, (1-4C)alcoxy; R3 represents OH, NO2, CN, fluoridated with (1-4C)alkoxy, (1-4C)alkoxy(2-4C)alkoxy. hydroxy(2-4C)alkoxy, (1-4C)alkoxycarbonyl, R7, R8-amino, R9, R10-amino, R9, R10-aminocarbonyl, R9, R10-aminosulfonyl or phenyl(1-4C)alkoxy, where phenyl ring in composition phenyl(1-4C)alkoxy is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R4 represents R11-phenyl or R11-(4-5C)heteroaryl, which represents heteroaromatic group, containing 4-5 carbon atoms and at least one heteroatom, selected from N and S, where phenyl or heteroaryl group is optionally additionally substituted with one or several substituents, selected from nitro, (1-4C)alkyl, (1-4C)alkoxy; R7 represents H, (1-4C)alkyl; R8 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl, (1-4C)alkoxy(1-4C)alkylcarbonyl, furylcarbonyl; phenyl(1-4C)alkylcarbonyl, where phenyl ring is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R9 and R10 are not necessarily selected from H, (1-6C)alkyl and (1-4C)alkoxy(2-4C)alkyl; or R9 and R10 can be bound together with formation of morpholinyl ring; R11 represents H, R12, R13-amino, R14, R15-aminocarbonyl or R14, R15-aminosulfonyl; R12 represents H; R13 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyperazinyl(1-4C)alkylcarbonyl; R14 and R15 are independently selected from H, (1-6C)alkyl, (1-4C)alkoxy(2-4C)alkyl and imidazolyl(1-4C)alkyl; X represents O or R16-N; Y represents CH2 or C(O);Z represents CN; R16 represents H, (1-4C)alkyl, (1-4C)alkylcarbonyl; or their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition, as well as to application of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline derivatives by any of i.i. 1-10.

EFFECT: obtaining novel biologically active compounds, which possess agonistic activity with respect to FSH receptor.

13 cl, 43 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) and their pharmaceutically acceptable addition salts having HIV replication inhibiting properties. In formula (I), R1 is halogen; R2 and R3 each independently denotes C1-6-alkyl. The invention also relates to a method for synthesis of said compounds and a pharmaceutical composition.

EFFECT: increased effectiveness of derivatives.

7 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: there is described a method of producing 1,4-diphenylazetidinone derivatives from properly protected β-substituted amino amides in the presence of silylation agents and at least one ring formation catalyst, where 1,4-diphenylazetidinone derivatives have general formula in which symbols, substitutes and indices assume values given in the formula of invention, where this ring formation catalyst is used as a cation in one of the following general formulae

where R16, R17, R18, R19 independently represent (C1-C15)alkyl, R41 represents (C1-C15) alkyl, R42 represents aryl, where the aryl can be substituted with -C(O)NH2, and as an anion of compounds with formulae or or or and symbols, substitutes and indices assume values given in the formula of invention, where residues from R20 to R32 and from R34 to R38 independently represent H, (C1-C6)alkyl, aryl and respectively two alkyl residues together can also form an aryl radical, which can be substituted again with F, O, Br, I, and where R39 and R40 together with 1,7,7-trimenylbicyclo[2.2.1]heptanyl, or a cation in that ring formation catalyst corresponds to the cation in general formula (XII), and the anion is R41O-, or the cation in that ring formation catalyst corresponds to the cation in general formula (XII), and the anion is R42COO-, where compounds of general formula in which, unless defined otherwise, symbols, substitutes and indices assume values given in the formula of invention, undergoes ring formation to obtain (pre)products of general formula from which the protection can be removed to obtain formula (I) compounds.

EFFECT: design of a novel method of producing target compounds.

10 cl, 30 ex

FIELD: chemistry.

SUBSTANCE: compounds of formula (I): , where: R1 is H, C1-6alkyl, C3-6cycloalkyl, phenyl, naphthyl; where the said C1-6alkyl can possibly be substituted with one or two substitutes selected from OH, NH2, guanidine, carbamoyl, COOH, C1-6alkoxy, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-C6alkylcarbonylamino, C1-6alkylS(O)a, where a equals 0-2, C3-6cycloalkyl, phenyl or indolyl; and where any of the said phenyl, indolyl can possibly be substituted with one or two substitutes selected from halogen, OH, C1-6alkyl, C1-6alkoxy; R2, R5 independently represents H, branched or straight C1-6alkyl, C3-6cycloalkyl, phenyl or naphthyl; where the said C1-6alkyl can possibly be substituted with one or more OH, NH2, guanidine, CN, carbamoyl, COOH, C1-6alkoxy, phenylC1-6alkoxy, naphthylC1-6alkoxy, indolyl, imidazolyl, naphthyl, (C1-C4)3Si, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkylS(O)a, C3-6cycloalkyl, phenyl, phenyl-C1-6alkylS(O)a, naphthyl-C1-6alkylS(O)a, where a equals 0-2; where any of phenyl, naphthyl, indolyl, imidazolyl can possibly be substituted with one or two substitutes selected from halogen, OH, C1-6alkyl, C1-6alkoxy; R3 is H, C1-6alkyl, halogen, C1-6alkoxy or C1-6alkylS-; R4 is H, C1-6alkyl, halogen, C1-6alkoxy; R6 is H, C1-6alkyl, phenylC1-6alkyl, naphthylC1-6alkyl; where R5, R2 can form a cyclopropane, cyclopentane ring, where R6, R2 can form a pyrrole ring; or its pharmaceutically acceptable salt; given the condition that the said compound is not 3-(R)-4-(R)-1-(phenyl)-3-[2-(4-fluorophenyl)-2-hydroxyethylsulphanyl]-4-[4-(N-{N-[(R)-1-(carboxy)-2-hydroxy)ethyl]carbamoylmethyl}carbamoylmethoxy)phenyl]-azetidin -2-one or 3-(R)-4-(R)-1-(phenyl)-3-[2-(4-flurophenyl)-2-hydroxyethylsulphanyl]-4-{4-N-((R)-α-{N-[(S)-1-(carboxy)-2-(hydroxy)ethyl]-carbamoyl}benzyl)carbamoylmethoxy]phenyl}azetidin-2-one.

EFFECT: obtaining compounds which are useful as cholesterol absorption inhibitors, enabling their use in pharmaceutical compositions.

18 cl, 136 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to method of producing compounds of formula VII: and intermediate compounds for producing said compounds. Values of Y, R1, R2, R3, R4, R5, X, n are given in paragraph 1 of the formula.

EFFECT: increased efficiency of the method of producing said compounds.

24 cl, 2 dwg, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new diphenylasetydione of formula (I): as well as to its pharmaceutically acceptable salts. Composition can be used as medical product for hyperlipidemia treatment. Method of its production and intermediate compound for its production is described.

EFFECT: production of new diphenylasetydione which can be used as medical product for hyperlipidemia treatment.

9 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention concerns a compound of the formula (I) , where A ring is selected out of phenyl or thienyl; X is selected out of -CR2R3-, -O- and -S(O)a-; where a is 0-2; Y is selected out of -CR4R5-, -O- and -S(O)a-; where a is 0-2; at least one -CR2R3- or -CR4R5- group is present; R1 is independently selected out of halogeno, C1-6alkyl and C1-6ealkoxy; b is equal to 0-3; R2 and R3, R4 and R5 are independently selected out of hydrogen, hydroxy, C1-6alkyl and C1-6alkoxy; or R2 and R3, R4 and R5 together form oxogroup; R6 is independently selected out of halogeno, C1-6alkyl and C1-6alkoxy; c is 0-5; R7 is independently selected out of halogeno, trifluoromethyl, trifluoromethoxy, methyl, ethyl, methoxy and ethoxy; d is 0-4; R9 is hydrogen or C1-4alkyl; R10 is hydrogen or C1-4alkyl; R11 and R12 are independently selected out of hydrogen, C1-4alkyl or carbocyclyl; where R11 and R12 can possibly be independently substituted for carbon atom with one or more substitute selected out of R25; R13 is hydrogen, C1-4alkyl or carbocyclyl; where R13 can possibly be substituted for carbon atom with one or more substitute selected out of R27; R14 is hydrogen, hydroxy, amino, carbamoyl, mercapto, sulfamoyl, etc; or R14 is a group of the formula (IA) , where Z is -N(R35)-; where R35 is hydrogen or C1-4alkyl; R15 is hydrogen or C1-4alkyl; R16 and R17 are independently selected out of hydrogen, hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C1-6alkyl, C1-6alkoxy, N-(C1-6alkyl)-amino etc; R18 is selected out of hydroxy, amino, carbamoyl, mercapto, sulfamoyl, C1-10alkyl, C1-10alkoxy, N-(C1-10alkyl)amino, N,N-(C1-10alkyl)2amino, etc; p is 1-3; q is 0-1; r is 0-3; m is 0-2; n is 1-2; where R1, R6, R7, R16, R17, R13, R9 can be equal or different; R25, R27 and R33 are independently selected out of hydroxy, amino, carbamoyl, mercapto, sulfamoyl, C1-10alkyl, C1-10alkoxy, C1-10alkoxycarbonyl, N-(C1-10alkyl)amino, etc; where carbocyclyl is a saturated, partially saturated or non-saturated monocyclic carbon ring including 3-6 atoms; or its pharmaceutically acceptable salt, solvate, or salt solvate. Compounds of the formula (I) or its pharmaceutically acceptable salts, solvates, or salt solvates are obtained by interaction of acid of the formula (IV) or its activated derivative with amine of the formula (V) . Compounds of the formula (I), where R14 is a group of the formula (IA), are obtained by interaction of compound of the formula (VI) , where R14 is carboxy, or its activated derivative, with amine of the formula (VI). Compounds of the formula (I), where X or Y is -S(O)a-, and a is 1 or 2, is obtained by oxidation of compound of the formula (I), where X or Y is -S(O)a-, and a is 0 (for compounds of the formula (I), where a is 1 or 2), or a is 1 (for compounds of the formula (I), where a is 2). The invention concerns pharmaceutical composition with inhibition effect on cholesterol absorption containing effective quantity of compound of the formula (I) combined with pharmaceutically acceptable dilutant or carrier, and combination of compound of the formula (I) and hydroxymethylglutaryl-coenzyme A (HMG Co-A) reductase inhibitor. Compounds of the formula (I) are applied to produce inhibition effect on cholesterol absorption or in hyperlipidemic state treatment of haematothermal animals.

EFFECT: obtaining diphenylazetidinone derivatives with inhibition effect on cholesterol absorption.

38 cl, 54 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes cyclic-substituted diphenylazethidinones of the formula (I): wherein each radical among R1, R2, R3, R4, R5 and R6 means independently of one another (C1-C30)-alkylene-(LAG)n wherein n = 1-2; one or two carbon atoms in alkylene residue are replaced with phenyl or piperazinyl residues or (C3-C10)-cycloalkyl residue; one or some carbon atoms in alkylene residue can be replaced with -S(O)n wherein n = 2; -O-, -(C=O)- or -NH-; hydrogen atom (H), fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J), O-(C1-C6)-alkyl; (LAG)n means mono- or tricyclic trialkyl ammoniumalkyl residue, -(CH2)0-SO3H, -(CH2)0-COOH, -(CH2)0-C(=NH)(NH2), and pharmaceutically acceptable salts also. Proposed compounds decrease the serum cholesterol content. Also, invention describes using these compounds for preparing a medicinal agent used in treatment of lipid metabolism disorders.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

7 cl, 1 tbl, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compounds of the formula (I): wherein R1-R5 mean independently of one another (C0-C30)-alkylene-(LAG)n wherein n = 1, and one or some C-atoms in alkylene residue can be replaced for -O-, -(C=O)-, -C=CH-, -NH-, hydrogen atom (H), fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J), (C1-C6)-alkyl, O-(C1-C6)-alkyl; (LAG)n means mono- or tricyclic trialkyl ammoniumalkyl residue or LAG can mean -(CH2)0-10-C(=NH)(NH2), -(CH2)0-10-C(=NH)(NHOH) or -NR7-C(=NR8)(NR9R10). Also, invention describes a medicinal agent for decreasing the serum cholesterol content and a method for its preparing. Proposed compounds are useful, for example, as hypolipidemic agents.

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

6 cl, 1 tbl, 34 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): wherein A1 means hydrogen atom (H), halogen atom, (C1-C5)-alkyl, group of the formula (a): ; A2 means (C1-C5)-alkyl, (C1-C5)-alkoxyl chain, (C1-C5)-alkenyl, hydroxy-(C1-C5)-alkyl, carbonyl-(C1-C5)-alkyl; A3 means halogen atom or group of the formula (a); A4 means (C1-C5)-alkyl, H, halogen atom, -COOR1, (C1-C5)-alkoxy-group, group of the formulae (a) and (b): wherein R1 means hydrogen atom, (C1-C5)-alkyl; R2 means -CH2OH, -COOR1; R3 means -OH, -OC(O)-R1; R4 means -(CH2)k-R5(CH2)l-; R5 means a simple bond (-), -CH=CH-, -OCH2-, carbonyl group or -CH(OH)-, and R4 is bound with tetrahydropyrane ring by the carbon-carbon bond; k and l = 0, 1 or a whole number above 1; k + l = 10 or lesser number; n = 0 or 1; p, g, r = 0 being one value among A1, A3 and A4 in the formula (I) must represent group of the formula (a), or to their pharmaceutically acceptable salts. Also, invention describes method for synthesis of proposed compounds. Proposed compounds of the formula (I) can be used as hypocholesterolemic agents for decreasing the serum blood cholesterol level.

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

5 cl, 3 tbl, 35 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel diphenylazethidinones substituted with acidic groups of the formula (I): , wherein one R1 or R2 means hydrogen atom (H) and another means atoms F, Cl, Br, J, -O-(C1-C6)-alkyl, (C0-C30)-alkylene-LAG wherein one or some carbon atoms in alkylene residue can be substituted for -O-, -NH-, -(C=O)-, -N(C1-C6)-alkyl-; LAG means -(CH2)1-10-SO3H, -(CH2)0-10-COOH; one R3 or R4 means H and another means atoms F, Cl, Br, J, (C0-C30)-alkylene-LAG wherein one or some carbon atoms in alkylene residue can be substituted for -O-, -NH-, -(C=O)-, -N-(C1-C6)-alkyl-; LAG means -(CH)1-10-SO3H, -(CH)0-10-P(O)(OH)2, -(CH2)0-10-O-P(O)(OH)2. -(CH2)0-10-COOH; n = 1-2; one R5 or R6 means H and another means atoms F, Cl, Br, J, and their pharmaceutically acceptable salts but compound 2-{[4-(4-{1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazethidine-2-yl}phenoxy)-butyl]methylamino}ethanesulfoacid and compounds wherein residues R1-R4 mean -O-(CH2)1-10-COOH, (C1-C6)-alkylene-COOH or -COOH are excluded. Compounds of the formula (I) possess the effect decreasing the cholesterol level and can be used as component of a medicinal agent.

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

7 cl, 1 tbl, 13 ex

The invention relates to reagents having the ability to remove hydrogen sulfide and mercaptans from gases, oil, oil, produced water, drilling fluids, and can be used on objects of oil production, refining, petrochemicals for their neutralization by neutralizing biogenic sulfur compounds

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, namely to development of a pharmaceutical composition for blood sugar and fat control, to a method of manufacturing of said pharmaceutical composition, to administration thereof. The pharmaceutical composition contains the following Chinese herbs or their extracts in mass portions: 5-17 privet fruits (Ligustri lucidui), 3-12 locoweed roots (Radix Astragali Mongolia), 1-5 gold-thread rhizomes (Rhizoma Coptidis), 1-5 lychee seeds (Semen Litchi), optionally 1-6 laminarias (Thallus Laminariae Japonicae) and 1-6 turmeric rhizomes (Rhizoma Curcumae Longae).

EFFECT: manufacturing of the pharmaceutical composition to be applied for treating diabetes.

10 cl, 27 tbl, 6 ex

Up!