Substituted quinolones having antiviral activity, synthesis method thereof, medicinal agent and use thereof in fighting viral infections

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to novel derivatives of quinolone or one pharmaceutically acceptable salts thereof, solvates thereof or solvates of salts thereof, having general formula I , in which R1 denotes fluorine, R3 denotes halogen, a hydroxy group or a C1-C4-alkoxy group, R4 denotes C1-C6-alkyl or C3-C8-cycloalkyl, where the alkyl can contain 1-3 substitutes, and the substitutes are independently selected from a group comprising halogen or trifluoromethyl, and where the cycloalkyl can contain 1-3 halogen atoms as substitutes, or R3 and R4 together with atoms to which they are bonded form a ring with a group of formula , in which * indicates a site for bonding with a carbon atom, and # indicates a site for bonding with a nitrogen atom, R7 and R8 independently denote halogen, trifluoromethyl, a monofluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, C1-C3-alkyl or C1-C3-alkoxy group, and R9 denotes hydrogen, halogen or C1-C3-alkyl, or R8 denotes a trifluoromethoxy group, and R7 and R9 denote hydrogen, R10 denotes a group of formula or , in which * indicates a site for bonding with a carbon atom, R2 is bonded in position 3 or 4 and denotes a hydroxy group, hydroxycarbonyl, aminocarbonyl, C1-C4-alkyl, C1-C4-alkoxycarbonyl, C3-C6-cycloalkylcarbonyl or optionally hydroxy-substituted C1-C6-alkylaminocarbonyl, where the alkyl is substituted with one substitute and the substitute is selected from a group comprising a hydroxy group, hydroxycarbonyl, aminocarbonyl, C1-C4-alkoxycarbonyl and 2-oxopyrrolidin-1-yl, R5 and R6 are independently bonded in positions 3, 4 or 5 and independently denote hydrogen, hydroxy group, methyl or ethyl, and Y denotes a methylene group or an oxygen atom. The invention also relates to methods of producing a compound of formula I, a medicinal agent based on the compound of formula I, use of the compound of formula I and a method of fighting viral infections.

EFFECT: novel substituted quinolone derivatives which are useful in treating viral diseases are obtained.

11 cl, 1 tbl, 69 ex

 

The text descriptions are given in facsimile form.

. The compound of the formula

in which R1denotes fluorine,
R3denotes a halogen, a hydroxy-group or1-C4-alkoxygroup,
R4stands With1-C6-alkyl or C3-C8-cycloalkyl, where alkyl may contain 1-3 substituent, and the substituents independently of one another selected from the group comprising halogen and trifluoromethyl, and where cycloalkyl may contain 1-3 halogen atom as substituents, or
R3and R4together with the atoms to which they are attached, form a ring group of the formula

in which * indicates the site of bonding with the carbon atom,
and
# specifies the location of binding to the nitrogen atom,
R7and R8independently of one another denote halogen, trifluoromethyl, monitortype, dipterocarp, cryptometer,1-C3-alkyl or C1-C3-alkoxygroup,
and
R9denotes hydrogen, halogen or1-C3-alkyl,
or
R8denotes cryptometer,
and
R7and R9denote hydrogen,
R10denotes a group of the formula

in which * indicates the site of bonding with the carbon atom,
R2attached in position 3 or 4 and represents what hydroxypropy,
hydroxycarbonyl, aminocarbonyl,1-C4-alkyl, C1-C4-alkoxycarbonyl,3-C6-cycloalkylcarbonyl or optional replacement1-C6-alkylaminocarbonyl,
where the alkyl is substituted by one Deputy, and the Deputy selected from the group comprising a hydroxy-group, hydroxycarbonyl, aminocarbonyl,1-C4-alkoxycarbonyl and 2-oxopyrrolidin-1-Il,
R5and R6independently from each other are attached in positions 3, 4 or 5 and
independently from each other denote hydrogen, a hydroxy-group, methyl or ethyl,
and
Y denotes a methylene group or an oxygen atom,
or one of its pharmaceutically acceptable salt, solvate or
the solvate salts.

2. The compound according to claim 1, characterized in that it is described by the formula

in which R1denotes fluorine,
R3denotes a halogen, a hydroxy-group or1-C4-alkoxygroup,
R4stands With1-C6-alkyl or C3-C8-cycloalkyl,
where alkyl may contain 1-3 substituent, and the substituents independently of one another selected from the group comprising halogen and trifluoromethyl, and
where cycloalkyl may contain 1-3 substituent of halogen,
or
R3and R4together with the atoms to which they are connected is ineni, form a ring group of the formula

in which * indicates the site of bonding with the carbon atom,
and
# specifies the location of binding to the nitrogen atom,
R7and R8independently of one another denote halogen, trifluoromethyl, monitortype, dipterocarp, cryptometer, C1-C3-alkyl or C1-C3-alkoxygroup,
R10denotes a group of the formula

in which * indicates the site of bonding with the carbon atom,
R2attached in position 3 or 4 and denotes a hydroxy-group,
hydroxycarbonyl, aminocarbonyl,1-C4-alkyl or C1-C4-alkoxycarbonyl,
where the alkyl is substituted by one Deputy, and the Deputy selected from the group comprising a hydroxy-group, hydroxycarbonyl, aminocarbonyl and C1-C4-alkoxycarbonyl,
R5and R6independently from each other are attached in positions 3, 4, or 5 independently from each other denote hydrogen, a hydroxy-group, methyl or ethyl, and
Y denotes a methylene group or an oxygen atom,
or one of its pharmaceutically acceptable salt, solvate or solvate of its salts.

3. The compound according to claim 2, characterized in that
R1denotes fluorine,
R3denotes the halo is Yong, the hydroxy-group or C1-C3-alkoxygroup, R4represents C1-C6-alkyl or C3-C6-cycloalkyl, where alkyl may contain 1-3 substituent, and the substituents independently of one another selected from the group comprising halogen and trifluoromethyl, and
where cycloalkyl may contain 1-3 substituent halogen, or
R3and R4together with the atoms to which they are attached, form a ring group of the formula:

in which * indicates the site of bonding with the carbon atom, and
# specifies the location of binding to the nitrogen atom,
R7and R8independently of one another denote halogen, trifluoromethyl, monitortype, dipterocarp, cryptometer,1-C3-alkyl or C1-C3-alkoxygroup, R10denotes a group of the formula

in which
* specifies the location of the binding carbon atom, R2attached in position 3 or 4 and denotes a hydroxy-group, hydroxycarbonyl, aminocarbonyl,1-C4-alkyl or C1-C4-alkoxycarbonyl, where the alkyl is substituted and the Deputy selected from the group comprising hydroxycarbonyl and C1-C4-alkoxycarbonyl,
R5and R6independently from each other are attached in polozheniyah, 4 or 5 and independently of each other denote hydrogen, a hydroxy-group, methyl or ethyl, and
Y denotes a methylene group or an oxygen atom, or one of its pharmaceutically acceptable salt, solvate or solvate of its salts.

4. The method of obtaining the compounds of formula (I) according to claim 1, characterized in that the compound of the formula

in which R1, R3, R4and R10have the meanings specified in claim 1, is introduced into reaction with the compound of the formula

in which R7, R8and R9have the meanings indicated in claim 1.

5. The method of obtaining the compounds of formula (I) according to claim 1, characterized in that the compound of the formula

in which R1, R3, R4, R7, R8and R9have the meanings specified in claim 1, is introduced into reaction with the compound of the formula
,
in which R10has the meaning indicated in claim 1.

6. The method of obtaining the compounds of formula (I) according to claim 1, characterized in that the compound obtained by the method according to claim 4, or a compound obtained by the method according to claim 5, and containing an ester group in the radical R10, hydrolyzing the base with the formation of the corresponding acid.

7. The connection according to one of claims 1 to 3, intended for the treatment and/or p is of opractice diseases, caused by viral infections.

8. Medicinal product for the treatment and/or prevention of viral infections comprising the compound according to any one of claims 1 to 3 in combination with an inert, non-toxic, pharmaceutically acceptable inert filler.

9. The use of compounds according to any one of claims 1 to 3 for the preparation of medicines intended for the treatment and/or prophylaxis of viral infections.

10. The use according to claim 9, wherein the viral infection is an infection with human cytomegalovirus (CPSC) or another representative of the group of herpes viridae (herpes viruses).

11. The way to combat viral infections, including the introduction of effective antiviral against the number of compounds according to any one of claims 1 to 3 or medicinal product of claim 8.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention refers to indole-3-yl-carbonyl-spiro-piperidine derivatives which have an effect of Vla-receptor antagonists and are presented by Formula I: where a tail spiropiperidine group A and residual R1, R2 and R3 are such as specified in the patent claim.

EFFECT: higher efficiency of applying the compounds in drugs effective in dysmenorrhea, hypertension, chronic heart failure, inadequate vasopressin secretion, hepatic cirrhosis, nephrotic syndrome, obsessive-compulsive disorder, anxious and depressive disorders.

22 cl, 42 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) or pharmaceutically acceptable salts thereof where R1 and R2 together denote a group selected form groups of formula (III-1): , where R9 denotes 1) a lower alkyl group, optionally substituted with a halogen atom or lower alkoxy group, 2) an aryl group, 3) an aralkyl group, 4) a heteroarylalkyl group, 5) a heteroaryl group, where the aryl, aralkyl, heteroarylalkyl and heteroaryl groups can be substituted with a halogen atom, lower alkyl group, optionally substituted with a lower alkoxy group or 1-3 halogen atoms, lower alkoxy group, optionally substituted with 1-3 halogen atoms, cyano group, hydroxy group, alkylsulphonyl group, cycloalkylsulphonyl group, aryl group, heteroaryl group, alkylaminocarbonyl group, alkanoyl amino group, alkyl amino group or dialkylamino group; R10 denotes a lower alkyl group, optionally substituted with 1-3 halogen atoms, or a lower alkylsulphonyl group; X9-X12 denotes a carbon atom or a nitrogen atom, where the carbon atom can be independently substituted with a lower alkyl group, optionally substituted with a halogen atom or a lower alkoxy group, lower alkoxy group, optionally substituted with a halogen atom, or a cyano group or a halogen atom; R3 denotes a) a group of formula (II-1): (ii-U where R4 and R5, taken together with a nitrogen atom, form a 5- or 6-member monocyclic ring, where the monocyclic ring may contain a substitute in form of a lower alkyl group, m1 equals 3; or b) a group of formula (II-2): , where R6 denotes a lower alkyl group or cycloalkyl group; m2 equals 1 or 2; X1-X4 all denote carbon atoms, or one of X1-X4 denotes a nitrogen atom and the rest denote carbon atoms; and where "heteroaryl" in each case relates to a 5- or 6-member aromatic ring containing 1-3 heteroatoms selected from a nitrogen atom, oxygen atom and a sulphur atom. The invention also relates to a histamine H3 receptor antagonist or inverse agonist, as well as a preventive or medicinal agent.

EFFECT: obtaining novel biologically active compounds, having histamine H3 receptor antagonist or inverse agonist activity.

11 cl, 8 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of structural formula I and their pharmaceutically acceptable salts. In structural formula I , X is oxygen; Y is oxygen; Y1 Y2, R7 and R4 represent H; X1 and X2 are independently selected from a group consisting of hydrogen, an alkyl group containing 1 to 5 carbon atoms, in which one or more hydrogen atoms of the alkyl group can be substituted with a halogen, aryl group containing 6 to 10 carbon atoms or a cycloalkyl group containing 3 to 9 carbon atoms, or a 5-9-member heterocyclic group with 2 heteroatoms selected from N and O, or a cycloalkyl group containing 5 to 9 carbon atoms; values of the rest of the radicals are given in the formula of invention. The invention also pertains to a pharmaceutical composition having properties of selective inhibitors of type IV phosphodiesterase, containing a therapeutically effective amount of the invented compound.

EFFECT: increased effectiveness of the compounds.

6 cl, 23 ex

FIELD: medicine; pharmacology.

SUBSTANCE: in formula (I) V represents -N (R1) (R2) or OR4; R4 represents H, C1-6alkyl, C1-6halogenalkyl or (C1-6alkylen)0-1R4' R4' represents C3-7cycloalkyl, phenyl, pyridyl, piperidinyl; and R4' is optionally substituted with 1 or 2 identical or different substitutes chosen from group consisting of C1-4alkyl, amino, C1-3alkylamino, C1-3dialkylamino, phenyl and benzyl; and each R1 and R2 independently represents L1, where L1 is chosen from group consisting from H, C1-6alkyl, C2-6alkenyl, C2-6alkinyl, - adamantyl, pyrrolidinyl, pyridyl, or R1 and R2 together with nitrogen atom to which attached, form X, where X represents pyrrolidinyl, piperazinyl, piperidinyl, morpholino; where X is optionally substituted with Y, where Y represents dioxolanyl, C1-9alkyl, phenyl, furanyl, pyrrolyl, pyridyl, pyrrolidinyl; and where X and Y are optionally split with Z, where Z represents -C1-3alkylen-, C1-3alkylen-. Other radical values are specified in formula of invention.

EFFECT: effective application for treatment of migraine and other headache mediated by action of CGRP-receptors.

34 cl, 11 dwg, 6 tbl, 201 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes novel spiroazacyclic compounds of the general formula: wherein X means -CH2, -CH2O, -OCH2 or oxygen atom (O); Y represents O; Z means -CH or nitrogen atom (N); R1 means (C1-C6)-alkyl optionally substituted with morpholinyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl, 2-oxoimidazolidinyl, imidazolidinyl, 2-oxooxazolidinyl, oxazalidinyl or (C3-C6)-cycloalkyl, (C2-C8)-alkyl ester or benzyl ester; m is chosen from group comprising 0 or 1; R4 means hydrogen atom or benzyl optionally substituted with halogen atom or (C1-C4)-alkyl; R5 means hydrogen atom or benzyl optionally substituted with halogen atom, (C1-C4)-alkyl or (C1-C4)-alkoxy-group; R6 means hydrogen atom or benzyl optionally substituted with (C1-C4)-alkoxy-, cycloalkyl-(C1-C4-alkoxy)- or halogen-(C1-C4-alkoxy)-group; R2 and R3 mean hydrogen atom and at least two radicals among R4, R5 and R6 mean optionally substituted benzyl. Also, invention relates to a method for inhibition of activity of serotonin 5-HT2A receptors, a method for treatment of state mediated by serotonin 5-HT2A receptors, and using spiroazacyclic compounds proposed.

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

35 cl, 3 tbl, 2 dwg, 45 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to substituted derivatives of 1-oxa-2,8-diazaspiro[4,5]dec-2-ene of general formula I in form of racemates, pure stereoisomers, particularly enantiomers or diastereomers in any ratio in mixture, in form of acids, or bases, or salts thereof, preferably physiologically acceptable salts, more preferably in form of hydrochlorides or solvates, in particular hydrates, wherein R1 and R2 are independently H, C3-C10-cycloalkyl, optionally substituted with O-alkylaryl, (C1-C12-alkyl)aryl, with the proviso, that at least one R1 and R2 is not H; R3 is H, SOR12 or COR13; R12 and R13 are independently C1-C10-alkyl, monocyclic 5-membered heterocyclic group having at least one heteroatom selected from sulfur atoms, optionally substituted with halogen; OR20, wherein R20 represents H, C1-C10-alkyl. Invention also relates to method for production of 1-oxa-2,8-diazaspiro[4,5]dec-2-ene of general formula I including a) compound of formula II interaction with methylenation agent, preferably with Ph3PCH3Br in presence of potassium tert-butylate in tetrahydrofuran (THF) to produce compound of formula III; d) compound of formula III interaction with ethylchloroximidoacetate of formula IV in presence of base, preferably of sodium hydrocarbonate or lithium hydroxide, preferably in organic solvent such as methanol, dichloromethane or TGF to produce 1-oxa-2,8-diazaspiro[4,5]dec-2-ene derivative of general formula V; c) compound of formula V interaction, directly or after previous saponification of functional group presenting in formula V (namely carboxylic acid ethyl ester) and optionally after activation of formed functional group (namely carboxylic acid) with amine of formula HNR1R2 wherein R1 and R2 are as defined above, to produce 1-oxa-2,8-diazaspiro[4,5]dec-2-ene derivative of general formula VI; d) protective group removing from compound of formula VI to produce compound of formula I, wherein R3 is H; and optionally e) converting of compound of formula I, wherein R3 is H, by treatment with acid chloride of formula R12SO2Cl to compound of formula I, wherein R3 is SO2R12 or converting by treatment with carboxylic acid chloride of formula R13COCl to compound of formula I, wherein R3 is COR13. Moreover disclosed is drug having analgesic action and containing at least one substituted 1-oxa-2,8-diazaspiro[4,5]dec-2-ene derivative of general formula I.

EFFECT: new drug with analgesic action.

11 cl, 6 tbl

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention describes 2-phenyl-substituted imidazotriazinones of the general formula (I): wherein R1 and R2 mean independently linear (C1-C4)-alkyl; R3 and R4 are similar or distinct and represent hydrogen atom or linear or branched (C1-C4)-alkenyl or (C1-C4)-alkoxy-group, linear or branched (C1-C6)-alkyl chain that can be broken by oxygen atom, and/or it can comprise from to some similar or different the following substitutes: methoxy-, hydroxy-, carboxyl, linear or branched (C1-C4)-alkoxycarbonyl, and/or residues of formulae -SO3H, -(A)a-NR7R8, -O-CO-NR7'R8', and/or wherein A means a number 0 or 1; A means residue -CO or -SO2; R7 and R8 mean hydrogen atom (H), cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl or pyridyl that can be substituted with different substitutes, methoxy-, (C1-C6)-alkyl and others; R7' and R8' mean (C1-C6)-alkyl. Also, other values of radicals R3 and R4 are given, a method for their preparing and a pharmaceutical composition. Described compounds are inhibitors of phosphodiesterases and can be used in manufacturing agents showing an anti-thrombosis, anti-proliferative, anti-vasospastic and vasodilating effect.

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

10 cl, 6 tbl, 337 ex

The invention relates to new derivatives of oxazolidinones General formula (I) listed in the description, as well as their salt

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula l where R1 represents CH2CI, CH2F or-C1-2alkyl-R3R4; R3 represents -O-; R4 represents phenyl, where said R4 group is optionally substituted by 0-5 groups J where J represents halogen; R2 represents C6-10aryl; or a group: where Y represents CH, AA2 represents C1-C7alkyl, R8 and R9 represents hydrogen or halogen; or a group: where Y represents CH, AA2 represents C1-C7alkyl, and R6 represents hydrogen, P4 represents -(T)p-R, where T represents -C(O)O-group, R represents C1-C12alkyl, and p is equal to 1; or a group: where A2 represents O, R7 and R8 together with atom whereto attached form a (10-14)members tricyclic unsaturated ring, e.g. carbazole; or a group: where AA2 represents C1-C7alkyl, and R15 represents 2-tert-butylphenyl. The declared compounds are caspase inhibitor prodrugs which under certain conditions can be transformed into biologically active compounds, particularly caspase inhibitors. Also, said invention refers to methods of producing said compounds and to a pharmaceutical composition exhibiting caspase inhibitory action on the basis of the said compounds.

EFFECT: what is produced are new compounds and based pharmaceutical composition which can find application in medicine for treating the diseases associated with inflammatory or degenerative conditions.

13 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles of general formula: where R=H (a); CH3 (b); OCH3 (c); CI (d) which can be used as biologically active substances, fluorescent materials and for synthesis of phthalocyanines. The method involves synthesis of substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles through a reaction which takes place in two steps, where at the first step 4-bromo-5-nitrophthalonitrile reacts with sodium salts of substituted 3-phenylpropanoates in molar ratio 1:2, respectively, at temperature 19…25°C for 12-20 hours in dimethyl formamide (DMF) solution, after which the reaction mass is diluted with tenfold excess water with T=0…25°C. The released resinous residue is extracted with dichloromethane, thoroughly washed with water and chromatographed on silica gel. The eluent (solvent) is evaporated. The residue of the intermediate product is filtered and re-crystallised from alcohol. At the second step of the method, tin dichloride solution in concentrated hydrochloric acid is mixed with the solution of the obtained intermediate product in ethyl alcohol in molar ratio 3.5-4.5:1, respectively, at temperature 30...50°C and reaction time of 1-2 hours, after which the reaction mixture is diluted with tenfold excess water with T=0…25°C, and the precipitate is filtered and re-crystallised from alcohol.

EFFECT: obtaining novel heterocyclic dicyano-derivatives of benzoxazines.

1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

,

where R1 is selected from formulae

, and ,

n equals 0; R6 and R7 are independently selected from hydrogen, C1-C6alkyl, cyanoC1-C6alkyl, C3-C6cycloalkylC0-C4alkyl and C6arylC0-C4alkyl; or R6 and R7 together with a carbon atom to which they are bonded form a 6-member heterocycloalkyl with one nitrogen atom; wherein any alkyl in R6 and R7 can optionally contain a methylene group substituted with an O atom; wherein any aryl in R6 and R7 or formed by a combination of R6 and R7 can be optionally substituted with one radical independently selected from: halide, C1-C6alkyl, -XC(O)OR10; where X denotes a bond; R10 is independently selected from C1-C6alkyl; R8 is selected from C5-C9heteroarylC0-C4alkyl containing 2-3 heteroatoms independently selected from N, O and S; wherein any heteroaryl in R8 can be optionally substituted with one radical independently selected from: halide, C1-C6alkyl, C3-C6cycloalkyl; R2 denotes hydrogen; R3 and R4 are independently selected from hydrogen, C1-C6alkyl, C3-C6cycloalkylC0-C4alkyl and C6arylC0-C4alkyl; wherein any alkyl in R3 and R4 can optionally contain a methylene group substituted with a S(O)2 group; R5 is selected from C5-C6heterocycloalkyl with 1-2 heteroatoms selected from N and O, and NR12R13; where R12 and R13 are independently selected from C1-C6alkyl; as well as pharmaceutically acceptable salts and isomers thereof. The invention also relates to use of compounds of formula (I) in preparing a medicinal agent, and to a pharmaceutical composition having cathepsin S inhibiting properties, which contains a therapeutically effective amount of the compound of formula (I) in combination with a pharmaceutically acceptable filler.

EFFECT: obtaining compounds which can be used as cathepsin S inhibitors.

10 cl, 12 dwg, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to (5H-pyrazolo[1,5-c][1,3]benzoxazin-5-yl)phenylmethanone derivatives (I), useful as HIV viral replication inhibitors, as well as pharmaceutical compositions, use thereof as medicinal agents.

EFFECT: disclosed compounds are meant for preventing or treating HIV infection and treating AIDS.

7 cl, 2 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula I and to their physiologically compatible salts. In general formula I , X denotes identical or different groups =C(-R)- or =N-, wherein at least one =C(-R-)- is substituted by =N-; Y is -O-; R denotes identical or different hydrogen, halogen, (C1-C6)-alkyl; R1 denoes (C4-C16-alkyl, (C1-C4)-alkylene-(C6-C10)-aryl, (C1-C4)-alkylene-(C3-C12)-cycloalkyl, (C9-C10)-bicyclic ring, wherein the aryl can be singly or multiply substituted with (C1-C6)-alkyl; R2 denotes hydrogen; or R1 and R2 together with the nitrogen atom which it is bonded form a monocyclic, saturated 6-member ring in which separate members of the ring system can be substituted with -CHR4-; R4 denotes (C1-C6)-alkyl. The invention also relates to a pharmaceutical composition having inhibiting action on endothelial lipase (EL) and containing one or more compounds of formula I, to use of the disclosed compounds to prepare a medicinal agent and to methods of producing compounds of formula I.

EFFECT: high effectiveness of derivatives.

11 cl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention relates to azole derivatives of formula I , where: A denotes S, O; W denotes -(C=O)-; X are identical or different and denote =C(-R)- or =N-; Y denotes -O- or -NR1-; R denotes hydrogen, halogen, (C1-C6)-alkyl, nitro; R1 denotes hydrogen; R2 denotes (C5-C16)-alkyl, (C1-C4)alkyl-phenyl, where phenyl can be optionally mono- or poly-substituted with (C1-C6)-alkyl; R3 denotes hydrogen; or R2 and R3 together with the nitrogen atom bearing them can form a monocyclic saturated 6-member ring system, where separate members of this ring system can be substituted with 1 group selected from the following: -CHR5-, -NR5-; R5 denotes (C1-C6)-alkyl, trifluoromethyl; and physiologically acceptable salts thereof. The invention also pertains to methods of producing said compounds and a medicinal agent based on said compounds.

EFFECT: novel compounds and a medicinal agent based on said compounds are obtained, which can be used as hormone-sensitive lipase (HSL) or endothelial lipase (EL) inhibitors.

12 cl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of tetrahydrobenzoxazines

in which substitute R1 denotes a hydrocarbyl residue having 1-3000 carbon atoms, and substitutes R2, R3, R4 and R5 independently denote hydrogen atoms, hydroxyl groups or hydrocarbyl residues, having 1-3000 carbon atoms, respectively, and in which substitutes R3 and R4 or R4 and R5 with a partial structure -O-CH2-NR7-CH2-, bonded to the benzene ring, can also form a second tetrahydrooxazine ring, where R7 denotes hydrocarbyl residues having 1-3000 carbon atoms, provided that at least one of substitutes R1, R2, R3, R4, R5 or R7 are polyisobutenyl, having 3000 carbon atoms and the rest of the substitutes from the group R1, R2, R3, R4, R5 or R7, if they denote hydrocarbyl residues, have 1-20 carbon atoms, respectively, as anti-oxidants for stabilising mineral oil and fuel products against the effect of light, oxygen and heat. The invention also describes jet fuel and jet fuel additive concentrate containing tetrahydrobenzoxazine of formula (I).

EFFECT: preparation of stabilisers having improved stabilisation of nonliving organic material, particularly jet fuel against the effect of light, oxygen and heat.

9 cl, 14 ex

FIELD: chemistry.

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

,

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

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

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to methods for synthesis of compounds of formula (A), where R1 denotes halogen, C1-C6halogenalkyl, C1-C6alkoxy(C1-C6)alkyloxy or C1-C6alkoxy(C1-C6)alkyl; R2 denotes halogen, C1-C4alkyl or C1-C4alkoxy; R3 and R4 independently denote a branched C3-C6alkyl; and R5 denotes C3-C12cycloalkyl, C1-C6alkyl, C1-C6hydroxyalkyl, C1-C6alkoxy(C1-C6)alkyl, C1-C6alkanoyloxy(C1-C6)alkyl, C1-C6aminoalkyl, C1-C6alkylamino(C1-C6)alkyl, C1-C6dialkylamino(C1-C6)alkyl, C1-C6alkanoylamino(C1-C6)alkyl, HO(O)C-(C1-C6)alkyl, C1-C6alkyl-O-(O)C-(C1-C6)alkyl, H2N-C(O)-(C1-C6)alkyl, C1-C6alkyl-HNC(O)-(C1-C6)alkyl or (C1-C6alkyl)2N-C(O)-(C1-C6)alkyl, or their pharmaceutically acceptable salts which have renin inhibiting activity, as well as to basic intermediate compounds obtained during steps for synthesis of the desired compounds and to methods for synthesis of said intermediate compounds.

EFFECT: alternative synthesis method.

43 cl, 8 dwg, 11 ex

FIELD: medicine.

SUBSTANCE: invention refers to indole-3-yl-carbonyl-spiro-piperidine derivatives which have an effect of Vla-receptor antagonists and are presented by Formula I: where a tail spiropiperidine group A and residual R1, R2 and R3 are such as specified in the patent claim.

EFFECT: higher efficiency of applying the compounds in drugs effective in dysmenorrhea, hypertension, chronic heart failure, inadequate vasopressin secretion, hepatic cirrhosis, nephrotic syndrome, obsessive-compulsive disorder, anxious and depressive disorders.

22 cl, 42 ex

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