Composition and derivatives of substituted azaindoloxoacetapiperazine characterized by antiviral activity

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to new compounds of and formula: I II those developing antiviral activity allowing application in pharmaceutical formulations and for antiviral medicines production.

EFFECT: new compounds have useful biological properties.

5 cl, 3 dwg, 6 tbl, 3 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula I,

2. The compound of formula II,

3. Pharmaceutical composition with anti-virus activity containing a compound according to claim 1 or 2 and a pharmaceutically acceptable carrier.

4. The use of compounds according to claim 1 for the manufacture of tools for the treatment of viral diseases.

5. The use of compounds according to claim 2 for the manufacture of tools for the treatment of viral diseases.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to the formula I compounds or its pharmaceutically acceptable salt or hydrate where Z means N; X1 means O or S, R1 means alkyl containing one to six carbon atoms; R2 designates hydrogen or alkyl containing one to six carbon atoms; and R3 designates hydrogen or alkyl containing one to six carbon atoms substituted with the -ORa group where Ra means alkyl containing one to six carbon atoms; saturated nonaromatic cyclic radical containing 3 to 8 atoms in a cycle where one atom in a cycle is a heteroatom selected from N or O, whereas the rest of the atoms in the cycle are carbon atoms, one or two of these carbon atoms being not necessarily substituted by nitrogen atom with the groups -C(O)(C1-C6alcoxy) or -SO2-C1C6alkyl. Invention also relates to pharmaceutical composition.

EFFECT: compounds possess inhibiting activity.

13 cl, 1 tbl, 8 ex

FIELD: CHEMISTRY.

SUBSTANCE: invention relates to novel method for preparation of compounds of formula IX or IXа, which implies reaction of compound of formula Va, in solvent, with compound of formula VII or formula VIIa, in the presence of palladium catalyst and phospho ligand, in the presence of amine base, resulting in compound of formula VIII or VIIIa. The method also implies reaction of compound of formula VIII or VIIIa, in solvent, with cyclopropylamine, not necessarily in the presence of catalyst. Also, invention relates to method for purification of compound of formula IX or IXa.

Va - R1 may be either С1-8alkyl, aryl or heteroaryl, not necessarily aryl- and/or С1-8alkyl-substituted; and

.

EFFECT: method for preparation of biologically useful compounds is described.

17 cl, 3 tbl, 77 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I or pharmaceutically suitable salt or solvate thereof, where dashed line stands for additional bond, а is a number from 0 to 2, b is a number from 0 to 2, n is 2, p is 2, r is 1, М1 stands for nitrogen, М2 stands for С(R3), X stands for either a bond or alkylene group with number of carbon atoms from 1 to 6, Y stands for -С(О)- group, Z stands for a bond, or alkylene group with number of carbon atoms from 1 to 6, or alkenylene group with number of carbon atoms from 1 to 6, or -С(O)-, -CH(CN)-, -SO2- or СН2С(O)NR4- group, R1 stands for groups, R2 stands for six-membered heteroaryl ring with one or two heteroatoms chosen independently of each other from either nitrogen atom or N-O group, other atoms of the cycle being carbon, five-membered heteroaryl ring with one, two, three or four heteroatoms chosen independently of each other from nitrogen, oxygen or sulphur, other atoms of the cycle being carbon, R32 stands for substituded quinoline group, R32 stands for substituted aryl group, heterocycloalkyl group, cycloalkyl group with number of carbon atoms from 3 to 6, alkyl group with number of carbon atoms from 1 to 6, group, where the said six-membered heteroaryl ring or the said five-membered heteroaryl ring may be R6-substituted, R12 independently of others is chosen from an alkyl group with number of carbon atoms from 1 to 6, hydroxyl group or fluorine atom, provided in case R12 stands for hydroxyl or fluorine the rest of R12 cannot be bonded to a nitrogen-bonded carbon atom, or two R12 substituents form an alkyl bridge with number of carbon atoms from 1 to 2, which bonds two non-adjaicent carbon atoms of the ring, R13 independently of the others is chosen from an alkyl group with number of carbon atoms from 1 to 6, hydroxyl group, alcoxy group with number of carbon atoms from 1 to 6, or fluorine atom, provided in case R13 stands for hydroxyl or fluorine the rest of R13 cannot be bonded to a nitrogen-bonded carbon atom, or two R13 substituents form an alkyl bridge with number of carbon atoms from 1 to 2, which bonds two non-adjacent carbon atoms of the ring. See description for meaning of the other structural elements. Invention relates also to pharmaceutical compositions, as well as to application of compounds of formula I.

EFFECT: preparation of novel biologically active substances and pharmaceutical compositions.

20 cl, 659 ex

FIELD: medicine, pharmacology.

SUBSTANCE: compound formula I is described, including the pharmaceutically acceptable salts, , where: Z presents ; Q is taken from the group that consists of: -W - presents , and the pharmaceutical composition, application of compound formula (I) for preparation of antiviral medicine.

EFFECT: proposed compounds can be helpful in treatment of HIV and AIDS.

70 cl, 2 tbl, 129 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method (variants) for synthesis of racemic 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone and its (+)-enantiomer. The first variant of method for synthesis of racemic 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone involves step (e) and another variant involves steps (b)-(e). Method for synthesis of (+)-enantiomer involves the following steps (a)-(f): (a) interaction of 2,6-diaminopyridine with malic and sulfuric acids to form 2-amino-7-hydroxy-1,8-naphthyridine hydrosulfate that (b) is treated with phthalyl reagent in a solvent medium to form phthalimidylnaphthyridine of the formula (2): that (c) is chlorinated to form chloride of the formula (3): that (d) is reduced to hydroxyindolinone of the formula (4): that (e) is treated with 5-methyl-2-oxohexyltriphenylphosphonium halide to yield racemic 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone that (f) is separated and final (+)-2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone is prepared. Invention provides improving method for synthesis of 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone from 2-(7-chloro-1,8-naphthyridine-2-yl)-3-hydroxyisoindolinone-1-one based on using 5-methyl-2-oxohexyltriphenylphosphonium halide.

EFFECT: improved methods of synthesis.

13 cl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): that are antagonists of CRF receptors and wherein Ar means optionally substituted phenyl or monocyclic 6-membered heteroaryl comprising one heteroatom chosen from nitrogen, oxygen or sulfur atoms; R1-R4 have values given in the invention claim, or to their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of indicated compounds and to pharmaceutical compositions containing these compounds that are useful for administration to a patient suffering from diseases that are relived in therapy using antagonists of CRF receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

26 cl, 10 tbl, 17 ex

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention describes novel substituted pyrazoles of the general formula (I): wherein values of radicals Ar, Ar2, W, G, R5-R8, RZ and n are given in the invention claim. Also, invention relates to a pharmaceutical composition based on these compounds, using this pharmaceutical composition for manufacturing agent designated for treatment of asthma, and a method for inhibition of activity of cathepsin S. Compounds indicated above can be used in medicine.

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

27 cl, 3 tbl, 352 ex

FIELD: organic chemistry, medicine, biochemistry.

SUBSTANCE: invention relates to 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazine-1-ylpyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidine-7-one isethionate salt and to its crystalline forms. These substances show properties of selective inhibitor of cyclin-dependent kinase 4 (CDK4) and can be used in treatment, for example, of inflammatory and cellular proliferative diseases. Crystalline forms of salt show powdery roentgenogram in values 2θ about 8.7, 13.5 and 17.6 (form A); 5.1, 11.8, 12.1, 12.8, 13.1 and 14.7 (form B), and 8.4, 8.9 and 21.9 (form D). Also, invention relates to methods for preparing crystalline 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazine-1-ylpyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidine-7-one isethionate salt, to medicinal agent and its using for preparing a medicinal agent.

EFFECT: valuable medicinal and biochemical properties of compound.

23 cl, 5 tbl, 18 dwg, 12 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to a novel compound - ((1R,3S)-3-isopropyl-3-{[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine succinate of the formula: that possesses property of CCR-2 antagonist. Also, invention relates to a method for modulation of activity of chemokine receptors and a method for treatment, improvement, control and reducing risk of inflammatory and immunoregulatory disorder or disease, and to a method for improvement, control and reducing risk of rheumatic arthritis.

EFFECT: valuable medicinal properties of compound.

4 cl, 3 tbl, 5 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to novel polycyclic compounds of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7, cycle A, cycles B, X, Y and Z have values given in the invention claims and in description of the claim, and to their pharmaceutically acceptable salts also. Proposed compound possess an antitumor activity and can be used in treatment of oncological diseases. Also, invention relates to a pharmaceutical composition based on these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

23 cl, 1 tbl, 57 ex

FIELD: medicine, molecular biology, antibodies.

SUBSTANCE: invention relates to an antibody raised against CCR5 and comprising: (i) two light chains wherein each light chain comprises product of plasmid expression and designated as pVK:HuPRO140-VK (ATCC - PTA-4097), and (ii) two heavy chains wherein each heavy chain comprises product of plasmid expression and designated as pVg4:HuPRO140 HG2-VH (ATCC - PTA-4098), or plasmid designated as pVg4:HuPRO140 (mut B+D+I)-VH (ATCC - PTA-4099), or fragment of such antibody binding with CCR5 on a human cell surface. Invention relates to nucleic acid encoding light and heavy chains of antibody, expression vector, cell-host transformed with at least one vector, and a method for preparing antibody. Antibody is used as an active component in composition used for inhibition of infection of cells CD4 + HIV-1, and to a pharmaceutical composition used in treatment of a patient with HIV-1 infection. Also, invention relates to antibody conjugate against CCR5 and its using. Use of antibodies provides enhancing effectiveness of prophylaxis and treatment of HIV-1 infection.

EFFECT: valuable medicinal properties of antibody.

31 cl, 23 dwg, 3 ex

FIELD: organic chemistry, medicine, virology.

SUBSTANCE: invention relates to novel 5'-phosphonates of 3`-azido-3`-deoxythymidine of the general formula (I) possessing anti-HIV activity, and to using 5'-phosphonates of 3`-azido-3`-deoxythymidine as an active component for preparing drugs possessing anti-HIV activity. In compound of the general formula (I): at n = 0-2; R1 means (wherein X means -CH2, -NH, O); R2 means -NH-C(O)- (wherein R2 means H, (C1-C6)-alkyl, (C5-C7)-cycloalkyl), -HO(CH2)k- (wherein k = 2-4); at n = 0 R1 means -Cl3C; at n = 1-6 R1 means Cl-, Br-, J-, and at n = 2-6 R3 means -C(O)O- (wherein R3 means (C1-C6)-alkyl) at n = 2-6.

EFFECT: valuable medicinal properties of compounds.

3 cl, 2 tbl, 10 ex

FIELD: medicine, pharmacology, pharmacy.

SUBSTANCE: pharmaceutical composition comprises abacavir and alovudin taken in the ratio = (1-10):(200-800) and a pharmaceutical carrier for them. Package designated for a patient for treatment of poly resistant HIV comprises alovudin and abacavir and information instruction for using both alovudin and abacavir in combination. Use of abacavir in common with alovudin for treatment of polyresistant HIV wherein use involves simultaneous, combined or successive administration of alovudin and abacavir. Invention provides more inhibition of virus, suppression of virus for longer period, limiting safety for arising mutations and development of polyresistant HIV, and decreasing toxicity of drugs.

EFFECT: valuable properties and enhanced effectiveness of drugs.

10 cl, 1 tbl, 3 dwg, 2 ex

FIELD: medicine, polymers.

SUBSTANCE: invention relates to conjugates consisting of a water-soluble polymer of molecular mass from 200 to 20000 Da and representing polyethylene glycol or alkyl chain to which two molecules of synthetic peptides, not less, are bound by reactive functional group and wherein each peptide comprises amino acid sequence originating from region HR1 or HR2 of human immunodeficiency virus (HIV) gp41. Invention relates to methods for using these conjugates for delivery inhibition of to HIV target-cell by addition of indicated conjugates in the amount providing effective inhibition of cell infection with indicated virus. Also, invention relates to methods for preparing conjugates by functional adding of each molecule of synthetic peptide to polymer through reactive functional group.

EFFECT: valuable biological properties of conjugates.

27 cl, 2 dwg, 6 tbl, 6 ex

FIELD: organic chemistry of natural compounds.

SUBSTANCE: invention relates to novel compounds, namely, to N'-{N-[3-oxo-lupan-28-oyl]-9-aminononanoyl}-3-amino-3-phenylpropionic acid and its salts of the formula (I) given in the invention description. This compound shows antiviral activity, in particular, anti-HIV activity, and immunostimulating activity. Compounds of the formula (I) are nontoxic and can be obtained from betulin isolated from birch bark as available raw with the high yield.

EFFECT: valuable medicinal properties of compound.

4 tbl, 9 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of piperidine of the general formula (I): or their pharmaceutically acceptable salts or isomers wherein Q means nitrogen atom (N); X and Z are chosen independently from group consisting of -CH and N under condition that one or both groups among Q and Z mean N; R, R4, R5, R and R are chosen independently from group consisting of hydrogen atom (H) and (C1-C6)-alkyl; R1 means H, (C1-C6)-alkyl, R9-aryl-(C1-C6)-alkyl-, (C1-C6)-alkyl-SO2-, (C3-C6)-cycloalkyl-SO2-, fluoro-(C1-C6)-alkyl-SO2-, R9-aryl-SO2-, R9-heteroaryl-SO2-, -N(R22)(R23)-SO2-, (C1-C6)-alkyl-C(O)-, (C3-C6)-cycloalkyl-C(O)-, fluoro-(C1-C6)-alkyl-C(O)-, R9-aryl-C(O)-, CH3CH2-NH-C(O)- or R9-aryl-NH-C(O)-; R2 means H or (C1-C6)-alkyl, and R3 means H, (C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl-, (C3-C10)-cycloalkyl-, (C3-C10)-cycloalkyl-(C1-C6)-alkyl-, R9-aryl, R9-aryl-(C1-C6)-alkyl- or R9-heteroaryl under condition that each X and X doesn't mean N, or R2 and R3 in common mean =NOR10. Proposed compounds can be used as selective CCR5 antagonists. Compounds are useful in HIV treatment. Also, invention describes a pharmaceutical composition based on compounds thereof and combination with antiviral or anti-inflammatory agent.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 4 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention relates to method for reducing of LDL-cholesterol and/or triglyceride level increased due to therapy by HIV protease inhibitors in HIV-infected subjects. According to invention Atazanavir is administered in combination with other HIV protease inhibitor, metabolized cytochrom P450 monooxygenase in therapeutically effective amounts.

EFFECT: effective treatment due to Atazanavir ability to cytochrom P450 monooxygenase inhibition; increased concentration of HIV protease inhibitors without preparation dose.

3 cl

FIELD: medicine, biology, virology.

SUBSTANCE: invention involves creature of complex of membranotropic compounds providing target delivery of antiviral preparation to HIV-1/2 damaged focus and suppression of viral infection at initial and later steps of its development. Invention provides effect on more expanded targets of human immunodeficiency virus and blocking HIV-infection at the early steps of interaction virus/cell based on synergism of components in the proposed complex. Modifying agents of polyanionic matrix - norbornene or adamantine and peptide-simulators of HIV-1/2 co-receptor bind with different sites of gp120 of HIV-1 that excludes the competition possibility and reciprocal steric hindering in virus-specific pharmacophore-modifying agents. Invention can be used for prophylaxis of HIV-infection and AIDS treatment, and in research works for study of ligand-receptor interaction (of type surface viral proteins - cellular receptors).

EFFECT: valuable biological and medicinal properties of complex.

3 cl, 5 tbl, 2 dwg, 3 ex

FIELD: chemistry of peptides, virology.

SUBSTANCE: invention relates to novel chemical compounds, namely, to glycyrrhizic acid (GA) glycopeptide with glycyl-L-phenylalanine: 3-O-{2-O-[N-(β-D-glucopyranosyluronoyl)-glycyl-L-phenylalanine-N-(β-D-glucopyranosyluronoyl)-glycyl-L-phenylalanine)]}-(3β,20β)-11-oxo-olean-12-ene-30-oic acid possessing anti-HIV-1 activity. This compound shows less toxicity (CD50 = 250 mcg/ml) as compared with the known anti-HIV preparation azidothymidine (CD50 = 3.5 mcM) and elicits the expressed anti-HIV-1 activity of high effectiveness and inhibits accumulation of virus-specific protein p24 (ID50 = 0.73 mcg/ml) that by 170-fold lower as compared with GA. This compound exceeds GA by the selectivity index (IS = 342.5) by 30-fold in culture cells MT-4 infected with the strain HIV-1/EVK. Glycopeptide in the concentration 0.80 mcg/ml (ID90 = 0.80 mcg/ml) inhibits reproduction of virus by 90%. Anti-HIV-1 activity (inhibition of p24) of the proposed compound in the concentration 10 mcg/ml is similar with activity of azidothymidine in the dose 0.05 mcg/ml.

EFFECT: enhanced and valuable antiviral properties of compound.

3 tbl, 2 ex

FIELD: virology, biotechnology, medicine, biochemistry.

SUBSTANCE: invention relates to creature agents used in AIDS treatment. Invention proposes pentapeptide of the following structure: Tyr-Pro-Ile-Glu-MeHis of molecular mass 672 Da. Peptide is prepared from sea worm Polychaeta, Eunicidae viscera homogenate extract. Method involves the successive purification by hydrophobic chromatography and reversed-phase high-performance liquid chromatography. Invention expands assortment of natural non-nucleoside inhibitors of HIV reverse transcriptase.

EFFECT: valuable medicinal properties of agent.

3 tbl, 10 dwg

FIELD: medicine; narcology.

SUBSTANCE: method can be used in medicinal treatment of alcoholism. The method includes emetine hydrochloride administration. Initiation, frequency and daily dose are determined depending on degree of manifestation of pathologic drive to alcohol (PDA) and alcohol dehydrogenase (ADG) activity. Daily dose of emetine hydrochloride is up to 5 mg. During treatment with emetine hydrochloride and in remission, a patient is prescribed a diet, which contains alimentary products that serve as a raw material for endogenous ethanol synthesis.

EFFECT: invention provides the anole rehabilitation of the PDA function and endogenic ethanol homeostasis.

2 cl, 2 ex

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