Pterin analogues for treating bh4 sensitive condition

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula possessing action on a BH4 sensitive condition.

EFFECT: invention refers to a pharmaceutical composition containing said compound to applying the compound for preparing a drug for treating the BH4 sensitive condition, such as a vascular disease, a psychoneurological disease, hyperphenylalaninemia.

12 cl, 31 dwg, 20 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula:

or its pharmaceutically acceptable salt.

2. Pharmaceutical composition having activity against WN sensitive state, containing an effective amount of a compound according to claim 1 and a pharmaceutically acceptable diluent or carrier.

3. The pharmaceutical composition according to claim 2, in a form suitable for oral administration.

4. The pharmaceutical composition according to claim 2 or 3 in solid form.

5. The pharmaceutical composition according to claim 2 or 3 in liquid form.

6. The use of compounds according to claim 1 or a composition according to any one of claim 2 to 5 for the manufacture of a medicinal product for the treatment of sensitive WN state.

7. The use according to claim 6, in which sensitive VN condition is a vascular disease.

8. The use according to claim 6, in which sensitive VN condition is a neuropsychiatric disorder.

9. The use of claim 8, in which sensitive VN condition which is a neuropsychiatric disturbance, due to the deficiency of VN.

10. The use of claim 8, in which sensitive VN condition is a neuropsychiatric disease associated with decreased function of tyrosine hydroxylase or decreased function of the tryptophan hydroxylase.

11. The use of claim 10, in which a therapeutically effective amount of a compound according to claim 1 improves the function of tyrosine hydroxylase or function of the tryptophan hydroxylase.

12. The use according to claim 6, in which sensitive WN state is hyperphenylalaninemia.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are novel derivatives of hexahydro pyrazino [2,1-c][1,2,4]triazine of general formula (III) (values of radicals are given in invention formula), their pharmaceutically acceptable salts and application of said compounds for obtaining medication for treatment and prevention of acute myeloid leukemia.

EFFECT: obtaining medication for treatment and prevention of acute myeloid leukemia

3 cl, 3 ex, 6 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to substituted tetrahydropyrrolopyrazines of general formula I, wherein R1, R2 and R3 in each case independently mean hydrogen or groups R1 and R2 or R2 and R3 form a common cycle ; R4 and R5 in each case independently mean H; R6 means branched or unbranched saturated, unsubstituted C1-6-alkyl, or unsubstituted heteroaryl wherein heteroaryl is a 5- or 6-member aromatic residue containing 1 heteroatom specified in a group consisting of N, O and S, or means phenyl wherein phenyl is unsubstituted or single-substituted or double-substituted by 1 or 2 substitutes which in each case are independently specified in a group consisting of F, Cl, Br, I, CF3, C1-6-alkyl, O-C1-6-alkyl, and , or means unsubstituted phenyl attached through C1-3-alkyl chain; R4a, R5a and R6a in each case independently mean H; R7 means (CH2)tC(=O)R8, wherein t is equal to 1, (C=O)(CH2)mNR11R12, wherein m is equal to 1 or 2, C(=O)(CH2)n(C=O)R8, wherein n is equal to 1, 2 or 3, (CH2)sNHC(=O)R8, wherein s is equal to 1 or 2; R8 means NR9R10 or saturated, branched or unbranched, unsubstituted C1-6-alkyl; wherein R9 and R10 in each case independently mean H, saturated, branched or unbranched, unsubstituted C1-6-alkyl, or unsubstituted or saturated C3-8-cycloalkyl, or phenyl, or phenyl attached through C1-3-alkyl wherein the alkyl chain is saturated, branched or unbranched, and wherein phenyl in each case is unsaturated or single or double saturated by 1 or 2 substitutes which independently specified in a group consisting of F, Cl, Br, I, CF3, C1-6-alkyl, O-C1-6-alkyl, pyridyl, and , or unsubstituted heteroaryl attached through C1-3-alkyl wherein heteroaryl is a 5-member aromatic residue 1 heteroatom of which are specified in a group consisting of O and S, wherein the alkyl chain is saturated, branched or unbranched, or heterocyclyl, or heterocyclyl attached through C1-3-alkyl wherein the alkyl chain is saturated, branched or unbranched, and wherein heterocyclyl in each case is saturated, unsubstituted or single substituted by benzyl, and heterocyclyl contains cycloalkyl containing 5 to 6 atoms in a cycle wherein 1 or 2 carbon atoms are substituted by 1 or 2 heteroatoms which are specified in a group consisting of N; or both groups R9 and R10 mean (CH2)3-6, CH2CH2OCH2CH2 or CH2CH2NR14CH2CH2; wherein R14 means phenyl or phenyl attached through C1-3-alkyl wherein phenyl in each case is unsaturated or single substituted by a substitute whih is specified in a group consisting of F, Cl, Br, I, O-C1-6-alkyl, and , or R14 means C(=O)R13; wherein R13 means saturated and unbranched C1-6-alkyl or means phenyl condensed with heteroaryl wherein heteroaryl is a 6-member aromatic residue 1 heteroatom of which is specified in a group consisting of N; R11 and R12 in each case independently mean H, saturated, branched or unbranched C1-6-alkyl, or unsubstituted, saturated C3-8-cycloalkyl, C(=O)R20 or S(=O)2R13; wherein R20 means NR21NR22, or R20 means saturated, branched or unbranched C1-6-alkyl, or means saturated C3-8-cycloalkyl, unsubstituted or single substituted by phenyl, or means unsaturated heteroaryl wherein heteroaryl is a 5-member aromatic residue 1 heteroatom of which is specified in a group consisting of O, or means phenyl wherein phenyl is unsubstituted or single substituted by C1-6-alkyl or means phenyl attached through C1-6-alkyl which is unsubstituted or single substituted by a substitute specified in a group consisting of F, Cl, Br, I and CF3, wherein the alkyl chain is saturated or unsaturated, branched or unbranched; wherein R21 and R22 in each case independently mean H or saturated, branched or unbranched, unsubstituted C1-6-alkyl; in the form of bases and salts of physiologically acceptable acids. The invention also refers to methods for preparing them, to drug preparations for treating disorders or diseases related with at least partially KCNQ2/3 K+ canals containing such compounds.

EFFECT: there are prepared new compounds and based drug preparations which can find application in medicine for managing pain, epilepsy, migraine, panic conditions and urinary incontinence.

17 cl, 2 tbl, 91 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to fluorinated compounds of formula , where: D, G and L are independently selected from a group consisting of: CH, C and N, and J and M are independently selected from a group consisting of C and N, under the condition that one of J and M denotes C and the other denotes N, wherein at least two of D, G, M, J and L denote N; X denotes CH2; Y is absent; Z denotes NR1R2; R1 and R2 are independently selected from a group consisting of: hydrogen, C1-C10 alkyl, aryl and heteroaryl, which is associated with aromatic radicals having 6 ring atoms, where 1-2 of these ring atoms are N; each of which can be substituted with one or more halogen atoms; or R1 and R2, together with nitrogen to which they are bonded, form a heterocyclic ring having 5 ring members; R3 is selected from a group consisting of: halogen, C1-C10 alkyl; E denotes aryl which can be substituted with one or more fluoro-substitutes or one or more of the following substitutes: C1-C6 alkyl, QC1-C10 alkyl, QC2-C10 alkenyl, each of which can be substituted with one or more fluoro-substitutes, and where Q denotes O; m denotes a number from 1 to 2; under the condition that: R3 is a fluoro-substitute, or group E includes a fluoro-substitute, or group Z includes a fluoro-substitute, with the condition that E does not denote 4-fluorophenyl or a compound of formula , where D, G and L are independently selected from a group consisting of: CH, C and N, and J and M are independently selected from a group consisting of C and N, under the condition that one of J and M denotes C and the other denotes N, wherein at least two of D, G, M, J and L denote N; X denotes CH2; Y is absent; Z denotes NR1R2; R1 and R2 are independently selected from a group consisting of: hydrogen, C1-C10 alkyl, aryl and heteroaryl, which is associated with aromatic radicals having 6 ring atoms, where 1-2 of these ring atoms are N; each of which can be substituted with one or more of the following substitutes: chlorine, bromine, iodine; or R1 and R2, together with nitrogen to which they are bonded, form a heterocyclic ring having 5 ring members; R3 is selected from a group consisting of: chlorine, bromine, iodine, C1-C10 alkyl; E denotes aryl which can be substituted with one or more chlorine, bromine or iodine atoms, and/or one or more of the following substitutes: C1-C6 alkyl, QC1-C10 alkyl, QC2-C10 alkenyl, each of which can be substituted with one or more substitutes selected from chlorine, bromine, iodine or hydroxy, where Q denotes O, wherein when E denotes phenyl, E does not contain, as a substitute, iodine which is directly bonded to it at position 4; m denotes a number from 1 to 2; wherein at least one of Z, E and R3 includes iodine; under the condition that E does not denote 4-iodophenyl and under the condition that said compound is not a compound of formula (Ia), defined in the following table:

The invention also relates to a pharmaceutical composition based on the compound of formula (I) or (Ia), a diagnosis method, a method of treating said disorders, based on use of the compound of formula (I) or (Ia), and use of the compound of formula (I) or (Ia).

EFFECT: obtaining novel compounds useful in treating disorders in mammals, characterised by anomalous density of peripheral benzodiazepine receptors.

24 cl, 13 dwg, 9 tbl, 23 ex

FIELD: medicine.

SUBSTANCE: invention refers to an agent for activation of lipoprotein lipase containing a benzene derivative of general formula (1) which is used for preventing and treating hyperlipidemia and obesity. The invention also refers to the benzene derivatives of general formula (1a).

EFFECT: composition improvement.

8 cl, 6 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new bicyclic heterocyclic derivatives of general formula wherein radicals and symbols are specified in the patent claim. Said compounds are FGFR receptor (fibroblast growth factor receptor) inhibitors. The invention also refers to a method for preparing a preferential group of compounds of formula (I), to a pharmaceutical composition containing said compounds, and to the use of said compounds for treating diseases, e.g. cancer.

EFFECT: preparing the new bicyclic heterocyclic derivatives.

22 cl, 16 tbl, 422 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel bicyclic heterocyclic derivatives, which are compounds of formula where values of X1-X5, A, B, R1, R2, q are given in claim 1, as well as pharmaceutical compositions containing said compounds, and use of said compounds to treat cancer.

EFFECT: high efficiency of treatment.

22 cl, 43 ex

FIELD: chemistry.

SUBSTANCE: described are novel azolo[1,2,4,5]tetrazine derivatives of general formula I, where Het=3,5-dimethylpyrazol-1-yl, X=N, R=cyclopropylmethylthio or pentylthio; or Het=3,5-dimethylpyrazol-1-yl, X=CH, R=isopropylthil; or Het=imidazol-1-yl, X=CH, R=H, and use of said compounds and additionally compounds of general formula (I), where Het=3,5-dimethylpyrazol-1-yl, X=N, K=cyclopentylthio; or Het=3,5-dimethylpyrazol-1-yl, X=CH, R=H or phenylthio based on disclosed activity as inhibitors of protein kinase PknA, PknB Mycobacterium tuberculosis when treating tuberculosis patients.

EFFECT: high efficiency of treatment.

2 cl, 2 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted sulphamide derivatives of formula I: , in which n, m, R1, R2a-c, R3, R4, R5 and R6 are as described in claim 1, in form of a racemate, enantiomers, diastereomers, mixtures of enantiomers or diastereomers or a separate enantiomer or diastereomer, bases and/or salts of physiologically compatible acids. The invention also relates to a method of producing said compounds, a medicinal agent having antagonist action on bradykinin receptor 1 (B1R), containing such compounds, use of such compounds to produce medicinal agents, as well as sulphamide-substituted derivatives selected from a group of compounds given in claim 8.

EFFECT: providing novel compounds which are suitable as pharmacologically active substances in medicinal agents for treating disorders or diseases which are at least partially transmitted through B1R receptors.

13 cl, 581 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are produced new diazepane substituted compounds representing various heterocyclic systems, including condensed, pharmaceutical compositions containing said compounds.

EFFECT: producing the compounds and compositions for preventing and treating neurological and mental disorders and diseases with involved orexin receptors.

13 cl, 1 tbl

New compounds // 2458920

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or to its pharmaceutically acceptable salts wherein -A-(R1)a means a group; -B-(R2)b means a group specified in the patent claim 1, R3 means hydrogen; X means CH2 or O; and Y means CH2. Also, the invention refers to a pharmaceutical composition exhibiting FGFR inhibitor activity on the basis of the declared compound.

EFFECT: there are produced new compounds and based pharmaceutical composition which can find application in medicine for preparing a cancer drug.

8 cl, 1 tbl, 180 ex

FIELD: medicine.

SUBSTANCE: claimed is application of carbon-containing nanoparticles, representing carbon nanocapsule 10 nm in size, containing iron particles, for destructuring atherosclerotic lesions, formed on the walls of blood vessels. It is demonstrated that claimed carbon-containing nanoparticles, applied on the surface of atherosclerotic lesion, are capable of penetrating into its internal layers and modifying its structure: presence of nanoparticles in it combines with presence in it of segments of sparse collagen structures.

EFFECT: invention can be used for creation of novel efficient medication which makes it possible to destructure atherosclerotic lesions, formed on the walls of blood vessels.

4 dwg

FIELD: medicine.

SUBSTANCE: to reduce tachycardia in such patients used is ivabradin (coraxan) in dose 5-7.5 mg for 7-14 days with further supporting course in dose 5 mg to the moment of when preoperative reparation is finished.

EFFECT: application of ivabradin in preoperative period in case of manifest thyrotoxicosis instead of traditional beta-adrenoblockers makes it possible to weaken sympathetic impact on sinus node and increase chronotropic myocardium reserve, avoiding at the same time undesirable cardioplegic effects, characteristic of beta-adrenoblockers.

2 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to the use of 9-(2-diethylaminomethyl)-2-(3,4-dioxyphenyl)imidazo[1,2-a]benzimidazole dihydrobromide of formula I: as an agent possessing antiarrhythmic and hepatoprotective properties. The invention also refers to the use of 9-(2-diethylaminomethyl)-2-(3,4-dioxyphenyl)imidazo[1,2-a]benzimidazole dihydrobromide for preparing pharmaceutical compositions.

EFFECT: higher antiarrhythmic and hepatoprotective activity.

2 cl, 11 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to a method for detection of genetic predisposition in an individual with no clinical implications of ischemic heart disease (IHD) to developing myocardial infarction (MI). The invention may be used in cardiology for detection of genetic predisposition to developing myocardial infarction (MI). A combination of two pathogenetically MI-related polymorphisms representing single nucleotide substitutes C1019T in connexin-37 (Cx37) gene and G894T in endothelial NO-CHHTa3bi.(eNOS) gene are examined. A high degree of risk of developing MI in an individual being examined is stated by a combination of homozygous genotype TT in C1019T polymorphism of Cx37 gene and homozygous genotype GG in G894T polymorphism of eNOS gene.

EFFECT: invention enables specifying a group of high risk of developing MI among almost healthy persons for the purpose of taking primary prevention actions.

2 dwg, 7 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to dihydropyrazolone derivatives or of formula (I), where R1 denotes a heteroaryl group of formulae given below, where * denotes the linkage point with the dihydropyrazolone ring, A in each individual occurrence denotes C-R4 or N, wherein at most two ring members A represent N at the same time, E denotes O or S, R2, R3 and R4 are as defined in the claim. The invention also relates to a method of producing said compounds.

EFFECT: compounds of formula (I) inhibit HIF-propylhydroxylase activity and can be used to treat and/or prevent diseases, as well as for producing medicaments for treating and/or preventing diseases, particularly cardiovascular and haematologic diseases, kidney diseases, and for promoting the healing of wounds.

10 cl, 10 tbl, 178 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely new organic compounds, namely N,N'-substituted piperazines of general formula (I), wherein R1, R2: linear or branched alkoxy (C1C4), CH3C(=O)O; n=1-5; m=0-3; Z: C=O, SO2; X:C(=NH)NH2, C(=NH)NHC(-NH)NH2, G is low-molecular organic or mineral acid, sodium, potassium, ammonium cations or water influences the haemostasis system, showing antiagregant, anticoagulant and vasodilator properties, and to a method for preparing N,N'-substituted piperazines of formula 1 by reaction of N-substituted piperazines of general formula wherein R1, R2; linear or branched alkoxy (C1C4), CH3C(=O)O; n=1-5; m=0-3; Z: C=O, SO2; and 1H-pyrazole-1-carboxamidine, dicyane diamide and their salts in organic solvents or water at temperature 10-50C in the presence of bases.

EFFECT: new substance are promising for prevention and treatment of the disturbed haemostasis system.

12 cl, 10 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely new organic compounds, namely N,N'-substituted piperazines of general formula (I), wherein R1, R2: linear or branched alkoxy (C1C4), CH3C(=O)O; n=1-5; m=0-3; Z: C=O, SO2; X:C(=NH)NH2, C(=NH)NHC(-NH)NH2, G is low-molecular organic or mineral acid, sodium, potassium, ammonium cations or water influences the haemostasis system, showing antiagregant, anticoagulant and vasodilator properties, and to a method for preparing N,N'-substituted piperazines of formula 1 by reaction of N-substituted piperazines of general formula wherein R1, R2; linear or branched alkoxy (C1C4), CH3C(=O)O; n=1-5; m=0-3; Z: C=O, SO2; and 1H-pyrazole-1-carboxamidine, dicyane diamide and their salts in organic solvents or water at temperature 10-50C in the presence of bases.

EFFECT: new substance are promising for prevention and treatment of the disturbed haemostasis system.

12 cl, 10 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to chemical-pharmaceutical industry, medicine, pharmacology and represents medication for prevention and treatment of atherosclerotic lesion of blood vessels, as well as pre- and thrombotic states, which possesses hypolipidemic and anticoagulant and antithrombotic activity, and is made in dosed drug form in form of coated tablets, consisting of core, which contains active substance and auxiliary substances, characterised by the fact that core contains substance of sulfated arabinogalactan potassium salt as active ingredient, and ludipress, aerosol and sodium stearate as auxiliary substances, components in medication being in definite ratio in wt %.

EFFECT: invention ensures efficient treatment and prevention of atherosclerotic lesion of blood vessels, as well as pre- and thrombotic states.

4 cl, 5 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel purinyl derivatives of formula or , a stereoisomer thereof or a mixture of stereoisomers thereof, or a pharmaceutically acceptable salt thereof, where n equals 0, 1, 2 or 3; X is O, S or NR', where R' is hydrogen or methyl; Y is cycloalkyl, phenyl, benzo[1,3]dioxolyl or pyridyl, where the cycloalkyl, phenyl, benzo[1,3]dioxolyl and pyridyl are possibly substituted with one substitute selected from a group consisting of halogen, trifluoromethyl, cyano, nitro and amine; R1 is hydrogen, alkyl or alkoxy-alkyl; and Het is a pyrazolyl group which is substituted twice or more with substitutes selected from a group consisting of alkyl, hydroxy-alkyl, halogen, trifluoromethyl, alkoxy-carbonyl and phenyl. The invention also relates to pharmaceutical compositions which are useful for treating or relieving symptoms of diseases and disorders associated with activity of potassium channels.

EFFECT: novel compounds which can be used as potassium channel modulators are obtained and described.

12 cl, 16 ex

FIELD: medicine.

SUBSTANCE: invention relates to condensed bicyclic compounds, having affinity with mineralocorticoid receptor (VR) of formula [I] and formula [ii], as well as to pharmaceutical compositions on their basis. In general formula [I[ and [ii] ring A represents benzene ring, which has substituent R1, condensed with adjacent 6-membered heterocyclic ring, and said benzene ring additionally optionally is substituted with one or two substituent(s), selected from halogen atom and C1-8-alkyl group, R1 represents C1-8-alkylsulfonyl amino group or C1-8-alkyl aminosulfonyl group, R2 and R3 (a) are similar or different and represent group, selected from hydrogen atom, C1-8-alkyl group, and from 6- to 10-membered monocyclic or bicyclic aryl group (said aryl group is optionally substituted with halogen atom), (b) are combined with each other with formation of oxogroup or (c) are combined with each other on their ends together with adjacent carbon atom with formation of C3-10-cycloalkyl group, X represents the following group =N-, =C(R4)- or -CH(R4)-, R4 represents hydrogen atom, cyanogroup, halogen atom, C1-6-alkyl group, C2-6-alkenyl group, C3-10-dicloalkyl group, C1-7-alkanoyl group, carbamoyl group or C3-8cycloalkenyl group, Ar represents from 6- to 10-membered monocyclic or bicyclic aryl group, optionally containing one or several heteroatom(s), selected from sulphur atom, oxygen atom and nitrogen atom (said aryl group is optionally substituted with similar or different, one or two substituent(s), selected from halogen atom, cyanogroup, C1-8-alkyl group, trihalogen- C1-8-alkyl group and C1-8alkoxygroup), and dotted line represents presence or absence of double bond, Xa represents the following group =N- or =C(CN)-, RZ represents hydrogen atom or halogen atom, R25 and R35 represent alkyl group, and Ar3 represents phenyl group, optionally substituted with one or two group(s), which is(are) selected from halogen atom and trihalogenalkyl group.

EFFECT: compounds can be applied as antihypertensive medication.

15 cl, 18 tbl, 8 dwg, 71 ex

FIELD: veterinary medicine.

SUBSTANCE: calves are injected intramuscularly as a single dose the solution of ferroglucine-75 on the basis of 15 mg of iron per 1 kg of live weight of a calf, and glicopin is fed 6.0 mg/day in the morning for 6 days, starting simultaneously with the injection of ferroglucine-75.

EFFECT: method enables to normalise the antioxidant activity of the liquid part of the blood of newborn calves with iron deficiency anemia, to increase the reactivity of the animal organism, to reduce the risk of thrombotic complications, promotes normal growth and development of calves.

2 ex

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