Novel compounds derived from 5-thioxylose and therapeutic application thereof

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of 5-thioxylose of formula I

where radicals are described in the claim, as well as to a synthesis method thereof and use thereof as active substances in medicinal agents, especially for treating or preventing thrombosis or cardiac failure.

EFFECT: more effective treatment.

9 cl, 162 ex, 2 tbl

 

The text descriptions are given in facsimile form.

1. Derived tioxolone chosen from:
a) compounds of the formula

where R means a hydrogen atom or a C2-C6-acyl group,
R1represents a C1-C4-alkylsulfonyl group2- 6-acyl group, a group CONR'R" or group

in which X denotes a single bond, an oxygen atom, sulfoxyl group, group
-CO - or a group-SNON-,
Ra means a hydrogen atom, halogen, C1-C4is an alkyl group, triptorelin group, triptoreline group, cyano, C1-C4-hydroxyalkyl group, a C2-C4-acyl group1-C4-CNS group or a group NR'r R",
the substituents Rb and Rc independently of one another represent a hydrogen atom, a halogen atom, a C1-C4is an alkyl group, a cyano or C1-C4-CNS group,
R2means a hydrogen atom, a C1-C4is an alkyl group or halogen atom, and
the substituents R' and R" independently represent a hydrogen atom or a C1-C4is an alkyl group, optionally substituted phenyl, or together form with the nitrogen atom to which they are attached, a ring containing 5 or 6 carbon atoms; and
b) additive salts.

2. The compound according to claim 1, where the group R1represents a group of the formula

where Ra, Rb and Rc such as defined in claim 1.

3. The compound according to claim 1, where R is a hydrogen atom.

4. The compound according to claim 1, where R is a group of PINE trees3.

5. The method of obtaining from the organisations, characterized in claim 1, comprising the stages consisting of:
a) interaction of pyridine formula

where R1and R2such as specified in claim 1,
with the derived 5-toxicomanes formula

where Hal means halogen, preferably bromine, and R represents a C2-C6-acyl group, in an aprotic solvent in the presence of silver salts or zinc salts in anhydrous environment at a temperature of from 25 to 110°C for 1 to 10 h with the formation of compounds of the formula

where R, R1and R2such as defined for the source connection;
b) if necessary, the interaction of the compounds of formula I, obtained above, with a solution of ammonia in methanol to obtain the compounds of formula

in which R1and R2such as defined above; and
C) if necessary, the interaction of one of the compounds I or Ia, obtained above, with an acid by known methods to receiving the respective additive salt.

6. The method of obtaining the compounds described in claim 1, comprising the stages consisting in:
(a) the interaction of Tetra-O-acetyl-5-toxicomanes formula

where AC means acetyl group, with a compound of the formula
where R1and R2such as specified in claim 1,
in an aprotic solvent in the presence of a catalyst of the type of Lewis acid at a temperature of from 20 to 60°C for 1 to 2 h with the formation of compounds of the formula

where R1and R2such as defined for the source connection;
b) if necessary, the interaction of the compounds of formula I, obtained above, with sodium methylate in methanol to form compounds of formula

where R1and R2such as defined above; and
C) if necessary, the interaction of one of the compounds 1 or 1A, obtained above, with an acid to obtain the corresponding salt additive.

7. The compound according to any one of claims 1 to 4, or its pharmaceutically acceptable additive salt for use as pharmacologically active substances.

8. The use of compounds described in any one of claims 1 to 4, or its pharmaceutically acceptable salt additive for preparing a medicinal product intended for the prevention or treatment of thrombosis, especially venous thrombosis.

9. The use of compounds described in any one of claims 1 to 4, or its pharmaceutically acceptable salt additive for preparing a medicinal product intended for the prevention or treatment of heart problems is technote.



 

Same patents:

FIELD: pharmacology.

SUBSTANCE: invention concerns compounds of formula I, where R1, R4, R5, R6, R7, R8 is H; R2 is F; A is O; R3 is (C1-C6)-alkyl, and one, several or all hydrogen atoms can be substituted by fluorine; B is (C0-C15)-alkylene; X is CO or link; L is (C1-C6)-alkylene, where in each case one or two -CH2-groups can be substituted by NH, or (C2-C5)-alkenylene; Y is CO, NHCO or link; R9 is hydrogen, (C1-C6)-alkyl, (C1-C6)-alkylene-OH, (C1-C6)-alkylene-NH2 or (C0-C6)-alkylene-CONH2, where one or more CH2-groups of alkyl residue can be substituted by -OH, -OSO3H, -NH-SO3H, adamantly or sugar residue of formula , or R8 and R9 together with their carrier atom N form 5-7-membered saturated cycle Cyc2, where one or more CH2-groups of the cycle can also be substituted by O, NH, NSO3H, N-(C1-C6)-alkyl, and alkyl group can be substituted by -OH group; and pharmaceutically acceptable salts of the claimed compounds.

EFFECT: medicine for blood sugar level reduction, containing one or more compounds of formula I; application of compounds of the formula I in obtaining medicine for blood sugar level reduction and for 1st and 2nd type diabetes treatment.

10 cl, 1 tbl, 37 ex

FIELD: medicine.

SUBSTANCE: invention relates to pyrazol derivatives, represented by general formula: , where R1 - R6 take on values, determined in the invention formula; one of Q and T is a group, presented by the general formula: or a group, presented by the general formula: , whereas the other one represents C1-6 alkyl group, halogen (C1-6 alkyl) group or C3-7 cycloalkyl group; X, Y and Z take on values, determined in the invention formula; to their pharmaceutically acceptable salts that possess inhibitory activity in regard to SGLT1 human being.

EFFECT: possibility of application in pharmaceutical compositions for prevention or treatment of the disease, connected with hyperglycemia.

25 cl, 223 ex, 12 tbl

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to pyrazole derivatives, which are represented by general formula (I), as well as theirpharmacologically acceptable salts, which have inhibiting activity against human SGLT1, to pharmacological composition, inhibitor of human SGLT1 and based on them medications, to their application for producing pharmacologic composition and to intermediate compounds for their obtaining. where R1 represents H, hydroxy(C2-6)alkyl group, one of Q and T represents group, which is presented by general formula: or group, which is presented by general formula while another presents C1-6alkyl group; R2 represents hydrogen atom, C1-6alkyl group or group of formula: -A-R8, where A represents oxygen atom, and R8 represents C6hetherocycloalkyl group, containing oxygen atom as heteroatom; X represents simple bond or oxygen atom, Y represents C1-6alkylene group or C2-6alkylene group; Z represents carbonyl group or sulphonyl group; R4 and R5 are similar or different, and each represents hydrogen atom or C1-6alkyl group, which can have similar or different 1-3 substituents, selected from substituents (i) Values of sunstituents (i) are iven in invention formula.

EFFECT: obtaining of pyrazole derivatives and based on them medications.

28 cl, 3 tbl, 197 ex

FIELD: chemistry.

SUBSTANCE: invention concerns substituted heterocyclic fluorglucoside derivatives of the formula (I) , where R1 and R2 are independently F, H, or one of R1 or R2 residues is OH; R3 is OH or F, so that at least one of R1, R2, R3 residues is F; R4 is OH; A is O; X is C or N, so that if Y = S, X should be C; Y is N or S; m = 1; R5 is hydrogen, OH or (C1-C6)-alkyl optionally mono- or polysubstituted by fluorine; R6 is H or (C1-C6)-alkyl, if required; or, if Y = S, R5 and R6 form phenyl together with carbon atoms to which they are linked; B is (C1-C6)-alcandiyl or -CO-NH-CH2-; n = 2 or 3; Cyc1 is phenyl or thiophenyl; R7 is hydrogen, F, CI, Br, J, (C1-C6)-alkyl or (C1-C6)-alkoxy optionally mono- or polysubstituted by fluorine; R8 is hydrogen or halogen; R9 is hydrogen; or R8 and R9 together mean -CH=CH-CH=CH-, -CH=CH-C((C1-C6)-alkoxy)=CH- or -OH=CH-O- and together with carbon atoms to which they are linked form Cyc2, which is phenyl, optionally substituted (C1-C6)-alkoxy or furanyl respectively; and their pharmaceutically acceptable salts.

EFFECT: obtaining efficient medicine for sugar level decrease in blood.

7 cl, 1 tbl, 31 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of glucopyranosyloxypyrazole of the general formula: wherein R means hydrogen atom, lower alkyl, acyl, alkoxycarbonyl, acyloxymethyl or alkoxycarbonyloxymethyl; one of Q and T represents a group of the general formula: wherein P means hydrogen atom, lower acyl or alkoxycarbonyl but other radical means lower alkyl or halogen(lower alkyl); R2 means hydrogen atom, lower alkyl, alkoxy-, alkylthio-group, halogen(lower)alkyl) or halogen atom under condition that P doesn't represent hydrogen atom when R means hydrogen atom or lower alkyl. Also, invention relates to pharmaceutically acceptable salts of these compounds, pharmaceutical compositions used for prophylaxis of renal glucose re-absorption and eliciting the inhibitory activity with respect to human SGLT2, pharmaceutical combinations that are used for prophylaxis or treatment of diseases associated with hyperglycemia.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

36 cl, 1 dwg, 6 tbl, 48 ex

The invention relates to glucopyranosyloxy derivative of the formula (I), where R1represents a hydrogen atom or a lower alkyl group; one of Q1and T1represents a group of formula (II), while the other of them represents a lower alkyl group or a halo(lower alkyl) group; R2represents a hydrogen atom, a lower alkyl group, lower alkoxygroup, lower allylthiourea, halogen(lower alkyl) group or a halogen atom, or its pharmaceutically acceptable salts

-substituted derivatives of carboxylic acids" target="_blank">

The invention relates tosubstituted derivatives of carboxylic acids, characterized by the General formula (I), (II), (III) and (IV)

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or their pharmacologically acceptable (C1-C6)-alkyl esters, or their pharmacologically acceptable Amida, or their pharmacologically acceptable salts

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to composition for prevention and treatment of diseases and states, associated with platelet aggregation and platelet-induced thrombosis, including mixture of at least one flavonoid with free B-cycle, of at least one flavane and at least one agent, selected from group, consisting of injection anticoagulant agent, peroral anticoagulant agent, antiplatelet agent, anti-angina medication, non-steroid anti-inflammatory drug (NSAID) or selective cyclooxygenase-2 (COX-2) inhibitor (versions). Method of composition application.

EFFECT: compositions are efficient for prevention and treatment of diseases and states, associated with platelet aggregation and platelet-induced thrombosis.

32 cl, 14 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to derivatives of 4-aminocarbonylpyrimidine of formula (I).

EFFECT: invention is applicable as P2Y12 receptor antagonists for treatment and/or prevention of diseases or disease states of peripheral vessels, as well as vessels, supplying internal organs, vessels of liver and kidneys, in treatment and/or prevention of cardiovascular and cerebrovascular diseases and states, associated with aggregation of platelets, including thrombosis in humans and mammals.

26 cl, 500 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is offered the administration of heparin conjugated with 2-aminoethanesulfonic acid (taurine) of formula (1), synthesised with a condensing reagent - water-soluble 1-ethyl-3[3 (dimethylamino)propyl]carbodiimide as an anti-inflammatory and antineoplastic anticoagulant.

EFFECT: compound surpasses heparin in anticoagulating ability, has high anti-inflammatory activity, while antineoplastic activity is comparable with the effect of antineoplastic preparations (doxorubicin, cyclophosphan, vincristine).

5 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology and cardiology, and concerns reducing spontaneous erythrocyte aggregation (SEA) in arterial hypertension with impaired glucose tolerance.. That is ensured by the integrated treatment that involves the administration of lisinopril 10 mg once a day in the morning and metformin 500 mg twice a day for 2 months, as well as graduated static and dynamic physical activity, including daily swimming for at least 30 minutes a day.

EFFECT: complex of drug-induced and drug-free modalities ensure reducing the SEA for 2 months that in turn promotes normalised blood rheology and reduced risk of thrombotic complications in the case patients.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine and can be used for determination of selection of heparin application for prevention of thrombotic complications. For this purpose level of soluble fibrin-monomer complexes is determined in blood plasma by means of ortho-phenantroline test. If its value is lower than 15.0 mg/100 ml transdermal way of heparin introduction is used. If the value is higher than 15.0 mg/100 ml parenteral way of heparin introduction is used.

EFFECT: method ensures efficient prevention of thrombotic complications due to selection of way of heparin introduction depending on degree of intravascular thrombus-formation.

4 tbl

FIELD: medicine.

SUBSTANCE: there are offered versions of a monoclonal antibody specific to GPVI polypeptide, peptide or its naturally occurred version. A based antithrombotic composition and a method for preparing thereof are described. The versions of methods for inhibition and treatment of various thrombocyte aggregation mediated diseases are disclosed. An antithrombotic set and hybridoma for producing the monoclonal antibody are described.

EFFECT: use of the invention provides the antibodies inhibiting thrombocyte aggregation that can find the further application in medicine for treating various thromboses.

13 cl, 16 dwg, 9 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 3-cyclohexylaminomethylthiazole[3,2-a]benzimidazole dihydrochloride of formula I: , having immunotropic and anti-aggregation activity.

EFFECT: novel compounds have useful biological properties.

2 cl, 8 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 3-methyl-8-piperazino-7-(thiethanyl-3)-1-ethylxanthine hydrochloride of formula .

EFFECT: novel compound which can be used in medicine as an antiaggregation and disaggregation agent is obtained and described.

3 cl, 2 tbl, 1 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to biotechnology and specifically to obtaining versions of glycoprotein IV alpha polypeptide of human thrombocytes (GPIbalpha) and can be used in medicine to treat vascular disorders. Using a recombinant technique, a polypeptide is obtained, which contains substitutes in SEQ ID NO:2 selected from: Y276F K237V C65S; K237V C65S; Y276F C65S; or Y276F Y278F Y279F K237V C65S. The obtained polypeptide is used to inhibit bonding of leucocytes to biological tissue or for treating disorders associated with activation of thrombocytes.

EFFECT: invention enables to obtain GPIbalpha polypeptide which bonds with von Willebrand factor with affinity which is at least 10 times higher than in natural GPIbα polypeptide, and also has low affinity for bonding with alpha-thrombin, lower aggregation and/or high resistance to proteolysis relative the polypeptide with SEQ ID NO:2.

41 cl, 3 dwg, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to antithrombotic compound of formula (I) (oligisaccaride-spacer-A(I)), where oligosaccharide is negatively charged pentasaccharide residue of formula given lower, where R5 - OCH3 or OSO3-, charge is compensated by positively charged counterions, and where pentasaccharide residue is obtained from pentasaccharide which has AT-III mediated anti-Xa activity per se; spacer is, in fact, pharmacologically inactive movably bound residue, which has from 10 to 50 atoms long chain; A is residue of -CH[NH-SO2-R1] [CO-NR2-CH(4-benzamidin)-CO-NR3R4], where R1 - 4-methoxy-2,3,6-trimethyphenyl; R2 - H; NR3R4 is piperidinyl group or its pharmaceutically acceptable salt or derivative, where amino group of amidin residue is protected by hydroxyl or (1-6C) alcoxycarbonyl group; where spacer of formula I compound contains one covalent bond with biotin residue of formula -(CH2)4-NR-BT, where R - H or (1-4C)alkyl and BT is residue . Invention also relates to pharmaceutical composition based on formula I compounds for treatment or prevention of thrombosis or other connected with thrombin diseases.

EFFECT: elaboration of antithrombotic compound for treatment or prevention of thrombosis or other, connected with thrombin diseases.

6 cl, 3 tbl, 2 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to oncology, and can be used in treatment of mammary gland cancer (MGC). Method is realised in the following way. After confirmation of malignant character of tumour tissue in patient sampling of 200 ml of blood from peripheral vein into reservoir with hemopreservative is carried out, after that it is centrifuged with separation of plasma, which is combined with cyclophosphane in amount 400 mg/m2, doxorubincin in dose 40 mg/m2 is introduced into erythrocyte mass; both reservoirs are incubated in thermostat for 30 minutes at temperature 37°C. After that, sucking of blood from the place of tumour tissue sampling is carried out with further introduction into it of 200 mg of cyclophosphane diluted in 5 ml of physiological solution. Tissue of mammary gland around tumour is infiltrated with incubated plasma with cyclophosphane, and erythrocyte mass with doxorubicin is introduced intravenously by drop infusion.

EFFECT: application of the invention makes it possible to increase efficiency of MGC treatment due to creation of maximal concentration of chemical preparations in leision focus and prevention of tumour process dissemination.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: medication represents derivatives of nucleotides of general formula (I)

, where X is H or OR1; one or two of substituents R1, R2, R3 are monosaccharide residues, the remaining ones are hydrogen protons; B is nitrous base bound in α- or β-position.

EFFECT: obtaining medication for inhibiting human enzyme poly(ADP-ribose)polymerase-1.

1 cl, 1 tbl, 2 dwg, 6 ex

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