Method for treating patients at chronic glomerulonephritis

FIELD: medicine, nephrology.

SUBSTANCE: the present innovation deals with introducing mildronate per 0.25 g 4 times daily about 30 min before meals for 3 wk, and then - per 0.25 g thrice daily about 30 min before meals for 4 wk at the background of daily intake of dipiridamol at the dosage of 200 mg/d. If necessary, therapeutic course should be repeated in 6 mo. The innovation improves endothelial function that leads to suppressed inflammatory process in kidneys and their improved functional capacity.

EFFECT: higher efficiency of therapy.

1 ex, 1 tbl

 

The invention relates to medicine, namely to therapy related to the treatment of patients with chronic glomerulonephritis (CS).

Known methods of treatment pumps, which is to assign polyunsaturated fatty acids, tocopherol, vitamin E, alpha-arginine, angiotensin-converting enzyme inhibitors (ACEI), blockers of angiotensin II receptors, antioxidants, calcium antagonists (AK) dihydropyridine, gipolipidemicheskih drugs (statins), estrogen in women after the menopause(1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11).

The use of these drugs has a regulating influence on one of the links of the pathogenesis of immunocomplex formation process in CS, the largest value which attach to endothelial dysfunction, underlying various pathological conditions, including determines the degree of activity of process pumps. Each of them has certain undesirable effects, for example, ACEI in 1/3 of the patients cause severe dry cough; estrogens exert proinflammatory and prothrombinase effects; AK dihydropyridine reduce blood pressure and tachycardia and is not effective in the presence of an inhibitor of NO synthase; preferred statins in individuals with hyperlipidemia.

Moreover, at present, no major randomisierte the NoMAS study was not proved the high efficacy of these drugs in relation to correct endothelial dysfunction, including at CS. And so the search for new drugs aimed at normalization of endothelial dysfunction, underlie many pathological conditions (atherosclerosis, hypertension, inflammatory diseases, and others), is very important.

The closest in technical essence to the present invention is a method of treating CS by assigning enalapril maleate (Enap, the company KRKA) in an individually adjusted dose, provides hypotensive effect, from 5 to 20 mg 1 time a day for 6 weeks (7). The course of treatment Enap improves vasomotor endothelial function in 64,7% of patients; to reduce the aggregation capacity of platelets on average, 42%; lower levels of von Willebrand factor by 23%; the decrease in blood pressure (BP). In 23,5% of patients reported an improvement of endothelium-dependent relaxation, and 11.8% of patients this indicator has deteriorated.

Thus, the known method is not effective enough, so as not leads to normalization of endothelial function in patients with arterial hypertension, also Enap, as well as other representatives of ACEI, often causes prolonged admission dry cough, endothelization action is possible only when the dose providing a hypotensive effect in patients with arterial hypertension, is it unacceptable for persons with normal numbers And/A.

Studies on the effect of ACEI in patients with CS on endothelial function have not been conducted, although work on the effect of ACEI on for CS and nefropatia there are (9, 10).

The problem solved by the invention is to increase the effectiveness of treatment due to correction of endothelial dysfunction in patients with CS while reducing side effects and getting more pronounced and persistent effect, and prevent progression of the disease.

This task is achieved by a new method of treatment of CS, which is to assign pharmacotherapy, and appoint Mildronate 0.25 g for 30 minutes before a meal 4 times a day for 3 weeks and 0.25 g for 30 minutes to reception 3 times a day for 4 weeks on the background daily intake of dipyridamole dose of 200 mg per day, if necessary, treatment in 6 months repeat.

The drug Mildronate (dihydrate 3/2,2,2-trimethyl, hydrazine-propionate), a structural analogue γ-butirobetaina inhibition β-oxidation of fatty acids by decreasing the synthesis of endogenous carnitine and slow migration of activated long chain fatty acids across the membrane of mitochondria (12). The manufacturer of the drug PJSC Grindeks, Latvia (instruction).

Mildronate improves metabolic processes, has cytoprotective, cardiovascular, hypolipidemics them, hypoglycemic and immunocorrective properties, eliminates functional disturbances of the nervous system (12-19), which is very important in patients with CS to prevent disease progression and improve the quality of life of patients.

There is clinical experience using mildronata with ischemic heart disease, physical stress in athletes, the abstinence syndrome in chronic alcoholism, dishormonal cardiopathy, the case and retinopathy, acute and chronic disorders of the blood supply to the brain (13-19).

Usage data mildronata to ensure pumps and for the correction of endothelial dysfunction in the medical-scientific and patent literature are absent, thus, the proposed method meets the criteria of the invention of "novelty."

The method is as follows: after being diagnosed every day, Mildronate 0.25 g 4 times a day 30 minutes before meals for 3 weeks, and then 0.25 g 3 times a day 30 minutes before meals for 4 weeks in patients receiving dipyridamole dose of 200 mg per day, if necessary, treatment in 6 months repeat.

After completing the course of therapy assess the dynamics of the state of endothelium - dependent vasodilatation (EDVD) of the brachial artery using ultrasound duplex functional is on A.Celermayery et al. (20), the number of circulating blood endothelial endothelial cells (CDA) and renal functional reserve (PFR), which represents the difference between the glomerular filtration rate, defined on an empty stomach and after stimulation of protein load.

CS is immune inflammatory diseases of the kidneys, mainly affecting the glomeruli and is steadily progressing, gradually leading to the development of nephrosclerosis and chronic renal failure. Chronicity and progression of the disease contributes to the persistence of antigens in the circulation with damage to the endothelium, activation of coagulation and deposition of fibrin in the microvasculature of the kidney(1, 2, 3, 21, 22, 23, 24, 25).

The vascular endothelium is a hormonally active tissue, providing for the regulation of vascular tone and blood clotting, as well as the adhesion of leukocytes and platelets, permeability and vascular remodeling(4, 23, 24, 25).

Functional reorganization of the endothelium in inflammatory processes and various vascular diseases in increasing the production of free radicals leads primarily to breach the synthesis of endothelial relaxing factor - nitric oxide (NO), which causes vasodilatation, inhibits the proliferation of smooth muscle cells, has an anti-platelet agent is burnt and anticoagulant properties, thereby prevents vascular remodeling (11).

One of the principles of correction of endothelial dysfunction is the pharmacological stimulation of endothelium-dependent release of nitric monoxide(2, 11, 19).

The purpose mildronata with antioxidant, immunomodulatory, angio and cytoprotective properties, allows you to simultaneously act on immunopositive inflammation and the microcirculation of the kidney, lipid peroxidation and metabolism and thereby to neutralize the main causal factors in the development of endothelial dysfunction in CS.

Mode of administration and dose mildronata selected in the process of clinical observations of patients pumps with signs of endothelial dysfunction, as the use of lower doses and another mode had no significant positive treatment effect. The appointment of high doses mildronata did not increase therapeutic effect. Patients prescribed Mildronate on the traditional background for such options CS therapy dipyridamole at a dose of 200 mg per day, with desegregate property, based on the synergy of their interaction.

Example.

As an example, treatment pumps according to the proposed method provides a case history of the patient Smirnova AS, 35, who was in the Nephrology Department of the Regional clinically the coy hospital with a diagnosis of Chronic mesangiocapillary glomerulonephritis, isolated urinary syndrome.

Was admitted to the Department routinely with complaints about the presence of edema of the legs and face, dull pain in the lumbar region, periodically urine red color.

From the anamnesis revealed that he first changed the color of urine ("meat slops") after suffering a sore throat 12 years ago. When contacting the clinic revealed proteinuria and hematuria transient nature, and the state was regarded as "reactive kidney. However, during periodic medical examinations revealed minimal changes in the urine (daily proteinuria up to 0.2 g, erythrocyturia Nechiporenko to 2500). Because the patient felt well, I ignored the recommendations of the studies in stationary conditions. Two years ago, after hypothermia swelling and changes in the urine of nephritic character.

Was examined in the Nephrology Department and according to biopsy verified diagnosis of chronic mezangioproliferativnom glomerulonephritis with a minimal degree of inflammatory activity. Were assigned to the chimes 200 mg and Enap 5 mg per day.

Medications the patient has not taken regularly and the last 10 days before entering the marked deterioration.

At objective examination satisfactory. The position of an active, clear consciousness. Weight 76 kg, height - 178 with whom. The normal skin color and moisture. The subcutaneous layer is moderately developed. The thyroid gland is not enlarged. Swelling of legs, feet, paraorbital. A/D 130/85 mm Hg, heart rate of 78 beats per minute. The respiratory and digestive systems without significant deviations from the norm. Heart sounds are clear, regular rhythm. The apical impulse is displaced slightly to the left. Deep palpation of the kidneys moderately painful. The symptom of "tapping" positive on both sides.

Following studies were conducted.

1. Complete blood count: Hb - 135 g/l, erythrocytes - 4,4×1012/l, leucocytes - 6,3×109/l, eosinophils - 3%, stab - 5%, segmented - 56%, lymphocytes - 27%, monocytes 7%, and ESR - 14 mm/h

2. Urinalysis: Udis 1018 (fluctuations 1010-1018), protein - 1,11 g/l (daily proteinuria was 1.94 g), leukocytes to 6 in the field of view, erythrocytes 6-8 in the field of view, Nechiporenko erythrocytes 10.000.

3. Biochemical parameters blood glucose - 4.2 mmol/l, bilirubin to 18.6 µmol/l, urea - 6.6 mmol/l, creatinine - 110 µmol/l, fibrinogen - 4.0 g/l, protein 66 g/l, albumin is 54.5%, α1to-4.5%, α2-9,1%, β - 4,5% γ-globulins is 27.3%, Alt - 0,48, ASAT - 0,36.

4. Sample Rehberg: glomerular filtration - 80 ml/min, reabsorption - 98%.

5. Bacteriological examination of urine: no growth of microorganisms.

6. Ultrasound: P is at his left 12× 5 cm, right 11×6 cm, nephroptosis on the right of the I degree. The ratio of the layers is 1:1. Cup-pelvis system is somewhat condensed, the contours blurred.

7. The immunological: CD2-1,12, CD3-1,05, CD70-0,29, CD4-0,56, CD8-0,38, CD4/CD8-1,5 CD16-0,15, CEC - 180 ed, Ig A - 3.6 g/l, Ig M - 2.1 g/l, Ig G and 9.8 g/l, HCT test - spontaneous - 12,4%, stimulated and 15.3%.

8. Excretory urography: signs of pyelonephritis and anomalies of the kidneys was not detected.

9. Functional renal reserve (FPR) - 7%

10. Circulating dokumentalnye the endothelial cells (CDA) CL/100 μl.

11. Endothelium-dependent vasodilatation (EDVD) of the brachial artery with reactive hyperemia of 6.3%.

12. Morphological study neobiota - signs of chronic mezangioproliferativnom glomerulonephritis with symptoms of inflammatory activity and endothelial dysfunction.

On the basis of clinical, instrumental, laboratory and morphological data diagnosed chronic mezangioproliferativnom glomerulonephritis in the acute phase.

According to the proposed method, the patient is assigned Mildronate 0.25 g for 30 minutes before a meal 4 times a day for 3 weeks in hospital and 0.25 g for 30 minutes before a meal 3 times a day for 4 weeks on an outpatient basis after taking dipyridamole 200 mg daily.

Treatment with Mildronate patient peremeshalos, side effects are not identified.

During the examination in dynamics after 7 weeks of treatment with Mildronate positive effect on the following parameters:

clinical - improved health and swelling disappeared;

urinary syndrome - proteinuria decreased to 0.5 g/day, erythrocyturia 4.000;

glomerular filtration increased to 90 ml/min;

CD4/CD8 (immunoregulatory index) - 1,8;

functional renal reserve (FPR) increased to 15%;

the endothelial cells (CDA) - 4 cells/100 μl;

endothelium-dependent vasodilatation (EDVD) to 10.7%.

We have analyzed the results of treatment with Mildronate on taking dipyridamole 22 CS patients with signs of acute inflammatory process and phenomena of endothelial dysfunction in age from 23 to 35 years, mostly with mezangioproliferativnom option. The comparison group consisted of 15 patients with CS who received only dipyridamole.

Treatment of patients was well tolerated, adverse reactions to receiving mildronata not marked.

The results of studies of urine, renal function, endothelium-dependent vasodilatation and circulating endothelial cells are presented in table 1.

As can be seen from the data in the study group treated for 7 weeks Mildronate on the proposed method, showed a significant improvement of endothelial function, reduction of the prot is Nuria and erythrocyturia, the increase in functional renal reserve and immunoregulating index. In cases of negative clinical dynamics after 6 months patients re-treatment was conducted according to the proposed method.

The application of the proposed method allows to achieve a positive effect on endothelial function and immunoregulatory index, which undoubtedly contributed to the suppression of the inflammatory process in the kidneys and improve the functional capacity of the kidneys in patients with CS in contrast to patients in the comparison group, where significant positive dynamics of the studied parameters have not been set.

Thus, the proposed method of treatment to achieve the desired positive effect, namely to increase the efficiency of treatment of patients with CS with the phenomena of endothelial dysfunction by reducing side effects get more pronounced and persistent therapeutic effect and to prevent progression of the disease.

Table 1

The dynamics of the studied parameters in the application of the method of treatment of patients with CS
IndicatorsThe studied patients CS n=22Healthy individuals (n=15
Before the treatmentAfter the treatment
Proteinuria (g/day)1,24±0,230,84±0,17*≤ mg/day
Erythrocyturia Nechiporenko (cells/ml)6.876,8±126,44.244,3±96,5756,8±25,4
Functional renal reserve (%)7,3±2,112,613,1*19,7±4,8
Endothelium-dependent vasodilatation (%)8,4±1,911,7±1,5*14,3±2,9
Circulating desquamated endothelial cells (cells/100 ál)9,8±1,76,3±1,9*4,1±0,4
Note: * - significance of differences in parameters before and after treatment (p<0,05)

Sources of information

1. Soludo B. I. Nephrology. - SPb, 2002. - 780 C.

2. Nephrology. A guide for physicians / edited Yestereve. - M.: Medicine, 2000. - S.138-139 (688 S.)

3. Ryabov, S. Nephrology. A guide for physicians. SPb: Special Lit, 2000. - 519 S.

4. Shestakova M.V. endothelial Dysfunction is the cause or the consequence of the metabolic syndrome. // Russian medical journal, 2001. No. 2. - P.88-90.

5. Berkovich O.A., Bazhenov E.A., Volkov E.V., etc. the Effect of therapy with fenofibrate on endothelial dysfunction in patients with previous myocardial infarction at a young age // Ter. archive. - 2002, No. 1, S.43-47.

6. Sitnikova M., Maximov T.A., S.N. Kozlov. and others On the relationship of markers of endothelial dysfunction and renal hemodynamics in patients with heart failure and the impact of the long-term therapy with perindopril. // The wedge. pharmacology and therapeutics. - 2001, No. 10, 49-52.

7. Yakovlev V.M., Semenkin A.A., Yudin S.M., etc. Influence the treatment of enalpril the maleate on the function of vascular endothelium and platelet-endothelial relationship in patients with essential hypertension. // Ter. archive, 2000, No. 1. - P.40-44.

8. Bova A.A., Trichotoma AL Role of vasoactive endothelial factors in the development of hypertension. // Cardiology. - 2001, No. 7, P.57-58.

9. Katerina IM, Tareeva I.E., I. Gerasimenko, etc. the Use of angiotensin-converting enzyme inhibitors in chronic diffuse diseases of the kidneys. // Ter. archive, 1995, No. 5. - P.20-24.

10. Bugrov O.V., Katerina IM, Kichkine BC, Baltaeva T.A. Effect of angiotensin-converting enzyme inhibitor on the indicators of the functional status of the kidneys in patients with systemic scleroderma // Clinical pharmacology and therapeutics. - 2001, No. 10, P.17-20.

11. Mukhin I.V., Nikolenko V.Y., G.A. Ignatenko Role of nitric oxide in the pathogenesis of chronic glomerulonephritis (literature review) // Nephrology, 2003, No. 1. - P.41-45.

12. Calvinist IA Mildronate - mechanism of action and the prospects of it is applications. Riga: Publishing house of PJSC "Grindeks", 2001. - 39 S.

13. Nedosekin S.A., N. Petrova, Kutuzov SUPERVISION, Perene NB the Quality of life of patients with chronic heart failure. The effect of treatment with Mildronate. // Ter. archive, 1999, №8. - P.10-12.

14. Koselska O.A. Influence mildronata on exercise performance, hemodynamics and oxygen balance in the body of patients with angina: author. dis....Kida. the honey. Sciences. - Tomsk, 1990, 23 S.

15. Z.A. Suslina, Fedorova T.N., Maksimov M., Kim E.K. Antioxidant effect mildronata and alpha-carnitine in the treatment of patients with vascular brain diseases // Experimental and clinical pharmacology. - 2002, No. 3. - P.32-35.

16. Kunevich IV, Ryzhenkov BE. Anti-sclerotic action mildronata in the experiment // Pathological pharmacology and experimental therapy. - 2002, No. 2. - p.24-27.

17. Paleev N.P., Poryadin GV, Paleev F.N., Sanin Npeumonia mechanisms in the pathogenesis of inflammatory diseases of the myocardium. // Cardiology, 2001, No. 10. - P.64-67.

18. Teplyakov A.T., Senkevich T.V., Stepicheva T.A., Mamchur S.E. Myocardial cytoprotection inhibitor β-oxidation of fatty acids by Mildronate in monotherapy and in combination with β-blocker-atenolol in patients with myocardial dysfunction of the left ventricle // Cardiology, 2003, No. 12. - P.15-18.

19. Zadionchenko V.S., Adage the T.V. and, Mr. A.P. endothelial Dysfunction and arterial hypertension: therapeutic opportunities. // Russian medical journal. - 2002, No. 1, S.11-15.

20. Celermajer D.S., Sorenser K.E., Cooch V. M. et. al. Non-invasive detection of endothelian dysfunction in children and adults at risk of atherosclerosis. // Lancet, 1992, - Vol.340. - P.1111-1115.

21. The Stavskaya CENTURIES, Ryabov S. risk Factors for progression of chronic glomerulonephritis / Mater. II conference of Nephrology. - Pskov, 1989. - S.

22. Sagitova O.N., Salikhov I.G., Maksudov A.N. Immunogenetic risk factors for development and progression of chronic glomerulonephritis. // Nephrology seminar. Sat. works. - St. Petersburg, 1998. - S-187.

23. Niaudet P. The kidney in mithohondrial cytopathies editorial review // Kidney Jnt. - 1997/ - Vol 51. - P.1000-1107.

24. Remuzzi J. Understanding the nature of renal disease progression // Kidney Jnt. - 1997. - Vol 51, No. 1. - P.2-15.

25. Remuzzi J. unifying hypothesis for renal scarring linking protein trafficking to the different mediators of unjury // Nephrol. Dialys. Transplant. - 2000. - Vol 15, no 6. - P.58-60.

Method for the treatment of patients with chronic glomerulonephritis by pharmacotherapy, characterized in that the prescribed Mildronate 0.25 g 4 times a day 30 minutes before meals for 3 weeks and then at 0, 25 g 3 times a day 30 minutes before meals for 4 weeks on the background daily intake of dipyridamole dose of 200 mg per day, if necessary, treatment in 6 months repeat.



 

Same patents:

FIELD: organic chemistry, pharmacy, biochemistry.

SUBSTANCE: invention relates to new substituted 2H-pyrano[2,3-c] of the general formula (1) eliciting ability to inhibit activity of protein kinase. In the general formula (1) X represents oxygen atom or group NR3; R1 represents group -C(O)R4, optionally substituted and optionally condensed azaheterocycle; R2 represents optionally substituted hydroxyl group or optionally substituted amino-group; R3 represents hydrogen atom or inert substitute meaning optionally substituted low- or non-reactive radical including such as (C1-C7)-alkyl, (C2-C7)-alkenyl, (C2-C7)-alkynyl, (C1-C7)-alkoxy-group, (C7-C12)-aralkyl, heterocyclylalkyl, (C7-C12)-alkaryl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkenyl, phenyl, aryl, (C2-C12)-alkoxyalkyl, (C2-C10)-alkylsulfinyl, (C2-C10)-alkylsulfonyl, -(CH2)-O-(C1-C7-alkyl), -(CH2)m-N(C1-C7-alkyl)n, aryloxyalkyl, heterocyclyl wherein m and n have value from 1 to 7; R4 represents optionally substituted amino-group or hydrogenated optionally substituted azaheterocycle. Also, invention relates to combinatory and focused libraries consisting of compounds of the present invention and designated for the search of compound-hits and compound-leaders prepared by screening of these libraries for using in preparing medicinal agents.

EFFECT: valuable medicinal properties of compounds.

8 cl, 2 tbl, 6 ex

FIELD: organic chemistry, vitamins, medicine, pharmacy.

SUBSTANCE: invention relates to a new compound of the formula (I): wherein X means hydrogen atom or hydroxy group; R1 and R2 that can be similar or different mean hydrogen atom, (C1-C4)-alkyl; R3 means hydrogen atom, methyl group, fluorine or chlorine atom. Also, invention relates to its esters able to hydrolysis in vivo in combination with pharmaceutically acceptable acids. Also, invention relates to a pharmaceutical composition eliciting the inhibitory activity with respect to proliferation and promoting differentiation of cells and comprising the effective dose of compound of the formula (I) in common with pharmaceutically acceptable carriers and/or excipients. Also, invention relates to applying compound of the formula (I) for preparing a medicine used in treatment and prophylaxis of disease characterizing by abnormal differentiation of cells and/or proliferation of cells.

EFFECT: valuable medicinal properties of compounds.

13 cl, 3 sch, 3 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: method involves applying dietotherapy of zoosterol as 0.5% of aqueous solution in the amount of 100-200 ml in the morning 30 min before taking meals at a daily dose of 0.5-1.0 g in 21 days long course.

EFFECT: enhanced effectiveness in correcting metabolism disorders.

1 tbl

FIELD: organic chemistry, medicine, chemical-pharmaceutical industry, pharmacology, pharmacy.

SUBSTANCE: invention relates to a medicinal agent used for prophylaxis and treatment of diseases and disorders associated with dysfunction of benzodiazepine receptors. This medicinal agent comprises compound of the formula (I)

. Compound of the formula (I) elicits high cardioprotective, neurotrophic, renoprotective activity and enhanced bioavailability.

EFFECT: valuable medicinal properties of compounds.

5 cl, 1 tbl, 1 ex

Drug // 2234331
The invention relates to the field of pharmaceuticals, namely, to medicines, and can be used to adjust the chemical composition of food, for example, metabolic disorders in patients with chronic renal failure

The invention relates to new compounds of formula I and Ia in all their stereoisomeric forms or their mixtures in all ratios, and their pharmaceutically acceptable salts, which has antagonistic activity against vitronectin receptor

The invention relates to the creation of medicines in the form of herbal teas, which can be used for treatment of chronic pyelonephritis

The invention relates to medicine, namely to the production of medicines from animal products

FIELD: organic chemistry, medicinal biochemistry, pharmacy.

SUBSTANCE: invention relates to substituted benzimidazoles of the formula (I): and/or their stereoisomeric forms, and/or their physiologically acceptable salts wherein one of substitutes R1, R2, R3 and R4 means a residue of the formula (II): wherein D means -C(O)-; R8 means hydrogen atom or (C1-C4)-alkyl; R9 means: 1. (C1-C6)-alkyl wherein alkyl is linear or branched and can be free of substituted by one-, bi- or tri-fold; Z means: 1. a residue of 5-14-membered aromatic system that comprises from 1 to 4 heteroatoms as members of the cycle that represent nitrogen and oxygen atoms wherein aromatic system is free or substituted; 1.1 a heterocycle taken among the group of oxadiazole or oxadiazolone that can be unsubstituted or substituted; 2. (C1-C6)-alkyl wherein alkyl is a linear or branched and monosubstituted with phenyl or group -OH; or 3. -C(O)-R10 wherein R10 means -O-R11, -N(R11)2 or morpholinyl; or R8 and R9 in common with nitrogen atom and carbon atom with that they are bound, respectively, form heterocycle of the formula (IIa): wherein D, Z and R10 have values given in the formula (II); A means a residue -CH2-; B means a residue -CH-; Y is absent or means a residue -CH2-; or X and Y in common form phenyl. The cyclic system formed by N, A, X, Y, B and carbon atom is unsubstituted or monosubstituted with (C1-C8)-alkyl wherein alkyl is monosubstituted with phenyl, and other substitutes R1, R2, R3 and R4 mean independently of one another hydrogen atom, respectively; R5 means hydrogen atom; R6 means the heteroaromatic cyclic system with 5-14 members in cycle that comprises 1 or 2 nitrogen atoms and can be unsubstituted or substituted. Also, invention relates to a medicinal agent for inhibition of activity of IkB kinase based on these compounds and to a method for preparing the indicated agent. Invention provides preparing new compounds and medicinal agents based on thereof for aims for prophylaxis and treatment of diseases associated with the enhanced activity of NFkB.

EFFECT: valuable medicinal properties of compounds and composition.

4 cl, 7 tbl, 224 ex

FIELD: medicine, cardiology, pharmacy.

SUBSTANCE: invention proposes applying moxonidine as an active component in preparing pharmaceutical compositions designated for treatment of injuries of heart muscle caused by infarction. Indicated compositions promote to prophylaxis in the infarction progression and to treatment of its complications also.

EFFECT: valuable medicinal properties of composition.

3 cl, 1 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyanoaryl (or cyanoheteroaryl)-carbonylpiperazinyl-pyrimidines of the general formula and their physiologically acceptable salts that elicit the broad spectrum of biological activity exceeding activity of structurally related known compounds. In the general formula (I) R1 represents radical OR3 wherein R3 represents saturated hydrocarbon radical with linear or branched chain and comprising from 1 to 4 carbon atoms; R2 represents phenyl radical substituted with cyano-radical (-C≡N) or radical representing 5- or 6-membered heteroaromatic ring wherein heteroatom is taken among oxygen (O), nitrogen (N) or sulfur (S) atom and substituted with cyano-radical (-C≡N). Also, invention relates to methods for preparing compounds of the general formula (I) that involve incorporation of group of the formula:

into piperazinyl-pyrimidine compound or by the condensation reaction of corresponding pyrimidine with piperazine comprising group of the formula:

. Also, invention relates to pharmaceutical composition and applying these compounds. Compounds can be used for preparing medicinal agents useful in human therapy and/or for therapeutic applying in veterinary science as agents eliciting ant-convulsive and soporific effect or for the general anesthesia.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

13 cl, 7 sch, 8 tbl, 41 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of dihydropyrimidine of the general formula (I):

or its isomeric form of the formula (Ia):

that can be used, for example, for treatment and prophylaxis of hepatitis B. In indicated formulas R1 means unsubstituted phenyl or phenyl substituted once or many times with similar or different substitutes taken among the group including halogen atom, trifluoromethyl group, nitro-, amino-group, hydroxyl and alkyl with 1-6 carbon atoms, or residues of formulas:

, or ; R2 means residue of the formula -XR5 wherein X means a bond or oxygen atom; R5 means alkenyl with 2-4 carbon atoms or alkyl with 1-4 carbon atoms that can be unsubstituted or substituted with phenoxy-group; R3 means amino-group, alkyl with 1-4 carbon atoms or cyclopropyl; R4 means pyridyl that is substituted with up to three times with similar or different substitutes taken among the group including halogen atom, trifluoromethyl group, alkoxy-group with 1-6 carbon atoms and alkyl with 1-6 carbon atoms, and their salts. Also, invention relates to 3,5-difluoro-2-pyridincarboxyimidamide and 3,5-difluoro-2-pyridincarbonitrile that can be sued as intermediates products for preparing compounds of the formula (I) or (Ia) and to a medicinal gent.

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

10 cl, 2 sch, 4 tbl, 9 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of piperazinylalkylthiopyrimidine of the formula (I): wherein R1 represents hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkanoyl or di-(C1-C4-alkyl)-amino-(C1-C4-alkyl); R2 means hydrogen atom or benzyl substituted with 1-3 substitutes taken among the group consisting of (C1-C4)-alkyl, (C1-C4)-alkoxy-group, di-(C1-C4-alkyl)-amino-group, hydroxyl group and halogen atom; n = 2, 3 or 4, and to its pharmaceutically acceptable acid addition salt. Also, invention describes a method for preparing compounds and pharmaceutical composition based on thereof. Compounds are useful for treatment of diseases arising as result of the central nervous system injury.

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

14 cl, 3 tbl, 26 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of 5-phenylpyrimidine or their pharmaceutically acceptable acid-additive salts that elicit properties of antagonists of neuropeptide receptor neurokinin-1 (NK-1). This allows their applying for treatment of such diseases as Alzheimer's disease, cerebrospinal sclerosis, attenuating syndrome in morphine withdrawal, cardiovascular alterations and so on. Compounds of invention correspond to the general formula (I):

wherein R1 means hydrogen or halogen; R2 means hydrogen, halogen atom, (lower)-alkyl or (lower)-alkoxy-group; R3 means halogen atom, trifluoromethyl group, (lower)-alkoxy-group or (lower)-alkyl; R4/R4' mean independently hydrogen atom or (lower)-alkyl; R5 means (lower)-alkyl, (lower)-alkoxy-group, amino-group, hydroxyl group, hydroxy-(lower)-alkyl, -(CH2)n-piperazinyl substituted optionally with lower alkyl, -(CH)n-morpholinyl, -(CH2)n+1-imidazolyl, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl, (lower)-alkylsulfanyl, (lower)-alkylsulfonyl, benzylamino-group, -NH-(CH2)n+1N(R4'')2, -(CH2)n-NH-(CH2)n+1N(R4'')2, -(CH2)n+1N(R4'')2 or -O-(CH2)n+1N(R4'')2 wherein R4'' means hydrogen atom or (lower)-alkyl; R6 means hydrogen atom; R2 and R6 or R1 and R6 in common with two ring carbon atoms can represent -CH=CH-CH=CH- under condition that n for R1 is 1; n means independently 0-2; X means -C(O)N(R4'')- or -N(R4'')C(O)-. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds.

15 cl, 4 sch, 86 ex

The invention relates to new derivatives of 4-phenylpyrimidine and their pharmaceutically acceptable acid additive salts, which possess the properties of receptor antagonists neirokinina(NK-1), and can be used to treat diseases, oposredstvovanii NK-1 receptor, for example, headache, Alzheimer's disease, multiple sclerosis, cardiovascular changes, oedema, chronic inflammatory diseases and so on

The invention relates to new N-heterocyclic derivatives of the formula (I):

where: A means-OR1-C(O)N(R1R2or-N(R1R21; each X, Y and Z independently represents N or C(R19); each U represents N or C(R5), provided that U is N only when X represents N, and Z and Y denote CR19; each W represents N or CH; V denotes: (1) N(R4); (2) C(R4)H; or (3) the groupdirectly related to the group -(C(R14R20)n-A,denotes a 5-6-membered N-heterocyclyl, optionally containing 6-membered ring additional heteroatom selected from oxygen, sulfur and NR6where R6denotes hydrogen, optionally substituted phenyl, 6-membered heterocyclyl containing 1-2 nitrogen atom, optionally substituted 5-membered heterocyclyl containing 1-2 nitrogen atom, aminosulfonyl, monoalkylammonium, dialkylaminoalkyl,1-6alkoxycarbonyl, acetyl, etc

The invention relates to new nitrogen-containing aromatic 6-membered cyclic compounds of the formula (I) or their pharmaceutically acceptable salts, demonstrating excellent selective PDE V inhibitory activity

FIELD: veterinary medicine.

SUBSTANCE: method involves administering aqueous solution containing 4.5% of diamidine, in combination with 2.5% of primacine and 20% of polyethylene glycol-6000.

EFFECT: increased reliability of treatment results.

Up!