1-alkyl-2-alkylcarbamoyl-glycerins exhibiting antihypertensive activity, and method for preparing thereof

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to an agent exhibiting antihypertensive activity which represents 1-alkyl-2-alkylcarbamoylglycerins of general formula I . In formula I R means hydrocarbon radical -(CH2)nCH3 (n=10-18), R1 means methyl or ethyl. Also, the invention refers to a method for preparing the compounds of formula I. The method consists in the fact that parent 1-alkylglycerins of general formula II react with trimethylchlorosilane with using triethylamine in toluene medium at temperature -20°C to 0°C, then the reaction mass is added with appropriate alkylisocyanate and processed with ammonium bifluoride in methanol medium at room temperature.

EFFECT: preparation of the agent exhibiting antihypertensive activity.

2 cl, 7 ex

 

The invention relates to chemistry and medicine, namely to antihypertensive tools and methods for their preparation.

The LEVEL of TECHNOLOGY

The closest analogues in structure and biological activity are 1-alkyl-2-acetyl-glycerine formula

where R is a hydrocarbon radical With16-C18,

which display a marked hypotensive activity, but unstable because of the tendency of acetyl groups to migrate from position 2 of the molecule of glycerol in position 3, which leads to the loss of physiological activity throughout 10-30 minutes after their introduction into the bloodstream [1-5].

As the original 1-alkyl-glycerine used compounds of General formula [6, 7]:

where R is a hydrocarbon radical -(CH2)nCH3(n=10-18).

The technical result, which directed these inventions are getting new derivatives of 1-alkyl-2-allylcarbamate-glycerine containing in the 2-position of the molecule alkylcarboxylic group and with pronounced prolonged antihypertensive activity and the way they are received.

DISCLOSURE of INVENTIONS

1. The technical result is achieved by the fact that the proposed 1-alkyl-2-allylcarbamate-glycerine, the General formula

where (a) R - Ugledar who meets the radical -(CH 2)nCH3(n=10-18), R' is methyl;

b) R is a hydrocarbon radical -(CH2)nCH3(n=10-18), R' is ethyl,

having antihypertensive activity.

The present invention presents the chemical structure of new compounds in a series of 1-alkyl-glycerine, namely 1-alkyl-2-allylcarbamate-glycerine containing in the 2nd position of the molecule alkylcarboxylic group of General formula

where (a) R is a hydrocarbon radical -(CH2)nCH3(n=10-18), R' is methyl;

b) R is a hydrocarbon radical -(CH2)nCH3(n=10-18), R' is ethyl,

having antihypertensive activity.

The claimed compounds are crystalline substance white, insoluble in water, soluble in ethanol, methanol, a mixture of methanol and chloroform. The structure and identity of the claimed compounds were confirmed by elemental analysis, NMR data1N and IR spectra and thin layer chromatography.

2. The technical result is also achieved by the fact that the method for obtaining 1-alkyl-2-allylcarbamate-glycerine containing in the 2nd position of the molecule alkylcarboxylic group and with pronounced antihypertensive activity in which the original 1-alkyl-glycerine is subjected to interaction with trimethylchlorosilane in prisutstvie is triethylamine in an environment of toluene at -20÷0°C, then alkylsulfonates and subsequent treatment of the reaction mass byflorida ammonium in the medium of methanol at room temperature, as the original 1-alkyl-glycerine used compounds of General formula

where R is a hydrocarbon radical -(CH2)nCH3(n=10-18).

The proposed method is that the original 1-alkyl-glycerine is subjected to interaction with trimethylchlorosilane in the presence of triethylamine in an environment of toluene at -20÷0°C, then alkylsulfonates and subsequent treatment of the reaction mass byflorida ammonium in the medium of methanol at room temperature.

As the original 1-alkyl-glycerine used compounds of General formula

where R is a hydrocarbon radical -(CH2)nCH3(n=10-18).

Example 1. Getting 1-hexadecyl-2-methylcarbamoyl-glycerin.

To a solution of 3.67 g (0.012 mole) of 1-hexadecylamine and 1.17 g (0.012 mole) of triethylamine in 150 ml of toluene in an argon atmosphere at -20÷0°C was added a solution of 1.26 g (0.012 mole) of trimethylchlorosilane in 20 ml of toluene. The reaction mixture was kept at 0°C, add 2 ml of methyl isocyanate and leave overnight. Then filtered, removed in vacuum, the solvent, the residue is dissolved in 40 ml of hexane, was added 0.66 g (0.012 mole) of byflorida ammonium in 40 ml of methanol and the extracts from the plants is more for 4 hours at room temperature. The mixture is filtered through a layer of aluminum oxide is removed in vacuum, the solvent, add 150 ml of hexane, filtered, and removed under vacuum hexane and obtain 3.33 g (77%) of 1-hexadecyl-2-methylcarbamoyl-glycerol), TPL 59°C, Rf=0.3 (silica gel, ether-hexane=4:1). PMR (δ, ppm): 0.9 (3H, t) - CH3; 1.2 (28 N, s)

(-CH2-)14; 1.6 (2H, m) OSN2(CH2)14CH3; 2.8 (3H, s) CONHCH3; 3.0 (1H,O-CH2NCH2; 3.4-3.6 (4H, m) -CH2SNSN2-; 3.8 (1H, s) CH2OH; 4.9 (1H, m) OCONHCH3. IR spectrum (νmaxcm-1): 1700 (CO); 3300 (NH, OH). Found, %: C 67.05; 67.12; H 11.45; 11.13; N, 2.85; 2.94. C21H43NO4. Calculated, %: C 67.56; H 11.53; N, 3.75.

Received new derivatives of 1-alkyl-2-allylcarbamate-glycerine containing in the 2nd position of the molecule alkylcarboxylic group and with pronounced prolonged antihypertensive activity.

Example 2. Getting 1-hexadecyl-2-ethylcarbamate-glycerin.

To a solution of 3.67 g (0.012 mole) of 1-hexadecylamine and 1.17 g (0.012 mole) of triethylamine in 150 ml of toluene in an argon atmosphere at -20÷0°C was added a solution of 1.26 g (0.012 mole) of trimethylchlorosilane in 20 ml of toluene. The reaction mixture was kept at 0°C, add 2 ml utilizationof and leave overnight. Then filtered, removed in vacuum, the solvent, the residue is dissolved in 40 ml of hexane, was added 0.66 g (0.012 mole) of Vittoria and mania in 40 ml of methanol and incubated for 4 hours at room temperature. The mixture is filtered through a layer of aluminum oxide is removed in vacuum, the solvent, add 150 ml of hexane, filtered, and removed under vacuum hexane and obtain 3.8 g (85%) 1-hexadecyl-2-ethylcarbamate-glycerol), TPL 50°C, Rf=0.34 (silica gel, ether-hexane=4:1). PMR (δ, ppm): 0.9 (3H, t)-N3; 1.2 (28 N, s) (-CN2-)14; 1.6 (2H, m)N2OS16H33; 2.4 (2H, s) -CONHCH2CH3; 3.4 (2H, s)-NHCH2CH3; 3.6 (4H, m) - CONHCH2CH3; 5.2 (1H, m) -CH2NCH2. Found, %: C 67.91; 67.88; H at 10.82; 10.91; N, 3.10; 3.24. C22H45NO4. Calculated, %: C 68.21; N, 11.62; N, 3.62.

Received new derivatives of 1-alkyl-2-allylcarbamate-glycerine containing in the 2nd position of the molecule alkylcarboxylic group and with pronounced prolonged antihypertensive activity.

Example 3. Getting 1-octadecyl-2-methylcarbamoyl-glycerin.

To a solution of 7.74 g (0.02 mole) of 1-octadecylamine and 2.02 g (0.02 mole) of triethylamine in 200 ml of toluene in an argon atmosphere at -20÷0°C was added a solution of 3.01 g (0.02 mole) of trimethylchlorosilane in 40 ml of toluene. The reaction mixture was kept at 0°C, was added 4 ml of methyl isocyanate and leave overnight. Then filtered, removed in vacuum, the solvent, the residue is dissolved in 60 ml of petroleum ether, was added 1.1 g (0.02 mole) of byflorida ammonium in 60 ml of methanol and kept in a quiescent is e 4 hours at room temperature. The mixture is filtered through a layer of aluminum oxide is removed in vacuum, the solvent, add 200 ml of petroleum ether, filtered, and removed under vacuum of the solvent and receive 5.65 g (65%) of 1-octadecyl-2-methylcarbamoyl-glycerol), TPL 46°C, Rf=0.42 (silica gel, ether-petroleum ether=3:1). PMR (δ, ppm): 0.9 (3H, t) -CH3; 1.2 (30 N, s) (-CH2-)15; 1.6 (2H, m) OCH2(CH2)15N3; 2.8 (3H, s) CONHCH3; 3.0 (1H, O-CH2CHCH2; 3.4-3.6 (4H, m)N2SNAN2-; 3.8 (1H, c) CH2OH; 4.9 (1H, m) N3. Found, %: C 67.81; 67,75; N, 11.00; 11.21; N, 3.10; 3.04. With22H45NO4. Calculated, %: C 68.21, H 11.62, 3.62 N.

Received new derivatives of 1-alkyl-2-allylcarbamate-glycerine containing in the 2nd position of the molecule alkylcarboxylic group and with pronounced prolonged antihypertensive activity.

Example 4. Getting 1-octadecyl-2-ethylcarbamate-glycerin.

To a solution of 4 g (0.01 mole) of 1-octadecylamine and 1 g (0.01 mole) of triethylamine in 150 ml of toluene in an argon atmosphere at -20÷0°C was added a solution of 1.05 g (0.01 mole) of trimethylchlorosilane in 20 ml of toluene. The reaction mixture was kept at 0°C, add 2 ml utilizationof and leave overnight. Then filtered, removed in vacuum, the solvent, the residue is dissolved in 40 ml of petroleum ether is added 0.55 g (0.01 mole) of byflorida ammonium in 40 ml of the of ethanol and incubated for 4 hours at room temperature. The mixture is filtered through a layer of aluminum oxide is removed in vacuum, the solvent, add 100 ml petroleum ether, filtered, and removed under vacuum of the solvent and obtain 3.06 g (68%) of 1-octadecyl-2-ethylcarbamate-glycerol), TPL 42°C, Rf=0.44 (silica gel, ether-petroleum ether=3:1). PMR (δ, ppm): 0.9 (3H, t) - N3; 1.6 (N, C.) (-CH2-)15; 1.6 (2H, m)N2OS16H33; 2.4 (2H, s) -CONHCH2CH3; 3.4 (2H, s) -NHCH2CH3; 3.6 (4H, m) - CONHCH2CH3; 5.2 (1H, m) -CH2NCH2. Found, %: C 67.96; 68,11; N, 11.00; 11.11; N, 3.30; 3.26. With23H47NO4. Calculated, %: C 68.82, N 11.72, N 3.49.

Received new derivatives of 1-alkyl-2-allylcarbamate-glycerine containing in the 2nd position of the molecule alkylcarboxylic group and with pronounced prolonged antihypertensive activity.

The study of the synthesized compounds on the reduction of blood pressure was carried out on rats with renovascular hypertension and in rats with spontaneous hypertension, presented in examples 5, 6, 7.

Example 5. The study of the synthesized compounds for lowering blood pressure.

In the following experiments on laboratory animals, particularly rats, to obtain renovascular hypertension model is used Goldblatt - 1 clip - 2 buds or 1 clip - 1 kidney is. The imposition of renal artery clips, restricting blood flow, leads to activation of the renin-angiotensin-aldosterone system and to increase mean arterial pressure (BP). The degree of increase in HELL depends on the diameter of clip. Model 1 clip - 1 kidney involves the removal of one kidney. In this case, the initial rise in blood pressure is also caused by activation of the renin-angiotensin-aldosterone system, which eventually return to normal. The situation is aggravated by renal failure, accumulation of excess fluid in the body, and in the later stages of the disease high blood pressure is maintained by other mechanisms.

In the experiment used male Wistar rats with initial weighing 240-300 g Pre-anesthetized rat - teminal sodium 40 mg/kg, intraperitoneally was placed on the operating table in the position lying on their back with fixation of the limbs.. postoperative scar was treated streptocide. Arterial systolic pressure was measured in tail arteries in awake rats. Before measurement, the rat was placed in the box with thermally substrate with a temperature of 37°C for 10-15 minutes. On the tail of the rat wore a cuff that is connected through a buffer tank with a pressure gauge and a rubber pear. Near mA the Jeti had sensor, record changes in the circumference of the tail with the passage of the pulse wave. The sensor is a rubber tube filled with carbon powder. The signal from the sensor is amplified and recorded on an oscilloscope having a screen with afterglow. In the cuff blows air up to pressure, which completely stopped the blood flow in the tail artery. Then the air pressure in the cuff is slowly reduced and noted the level of pressure at which appeared the pulsation of the blood. This value of the pressure in the cuff is consistent with systolic blood pressure of the animal.

Experiments on awake rats was performed in a standard way: one experimental rat and one control were placed in a setup for measurement of HELL, where the rat had the opportunity to move freely, connecting the catheter to a pressure transducer and kept rats for 1 hour to adapt to the conditions of the experiment. After 1 hour for 20 min was performed record the original settings. Tested preparations on the basis of the obtained compounds of the experimental animal was administered orally, once, in olive oil at a dose of 5 mg/kg in a volume of 0.3-0.4 ml depending on the weight of the rat. Control rats received olive oil in the equivalent volume. Because according to preliminary data it was known that substances have a long action, record the D conducted intermittently, the parameters were recorded every 20 min to one hour and 10 hours of daylight in the first and second day of the experiment. One month after surgery for modeling renovascular hypertension "1 kidney - 1 clip animals were obtained with a spectrum of changes in blood pressure In each group was at least 10 animals. It is known that the simple removal of the kidney in rats does not lead to increase in HELL, the second kidney usually cope with the increased load. This "variability" reactions of animals in response to the standard procedure to remove one kidney and clipping of the arterial lumen of the second renal artery may be due to several reasons. First, animals have individual peculiarities of the diameter of the renal artery, for some rats, the imposition of standard diameter clips can be critical, for others it is insufficient for the development of hypertension. Secondly, it is possible that each animal has its own internal, individual pressure range at which the kidney to cope with the load, so the rise of pressure is small. Thirdly, possible errors during operation, for example insufficient shoulders tightly grouped clips and the diameter of the vessel in this case may be a bit more than intended. In a further experiment to investigate the effect of p is moralnego the introduction of the test drugs on blood pressure were selected animals with secondary pressure is higher than 145 mm Hg Oral administration of olive oil to the control animals did not lead to changes in average blood pressure both in the first and in the second day of the experiment. Feeding drugs caused a decrease of HELL, which is the second hour of the first day of the experiment was approximately 20 mm Hg During the second day of this fall was significant, HELL decreased by 50-55 mm Hg, starting with the 4th hour of the experiment.

The investigations showed that all the synthesized compounds in oral single dose gradually and extended, not less than 2 days, the term reduces HELL.

Example 6. The study of the synthesized compounds for lowering blood pressure.

Rats Okamoto and Aoki development of hypertension is determined genetically and this line is a model of essential hypertension, or hypertensive man. 2 days before the experiment the animals under General anesthesia 500 mg/kg urethane and 70 mg/kg ∝-chloralose, intraperitoneally - implanted polyethylene catheters in the dorsal aorta through the femoral artery for registration of blood pressure (BP) and heart rate (HR) and in the inferior Vena cava through the femoral vein for injection of the study drug. The registration of these hemodynamic parameters was performed on awake animals free behavior to what it was described above. Rats were divided into 2 groups: experimental animals, which were injected drugs dissolved in liposomes (1 mg/ml), and the control, which was introduced only liposomes. The experience started after adaptation of the animal to the experimental environment for at least 1 hour. Drugs obtained on the basis of the proposed compounds were administered by infusion at a dose of 1 mg/kg for 30 seconds. Statistical processing of data was performed by non-parametric criterion of Mann-Whitney for comparison of control and test groups and non-parametric criterion of Wilcoxon for paired samples for comparison with the background values. Synthetic metabolites factor platelet aggregation caused a marked reduction in blood pressure, which reached a maximum after approximately 50 minutes after administration of the drug. Within 1 hour after drug administration, the average blood pressure in the experimental group most fell on average by 26±5 mm Hg (17±3%, p<0.05) as compared with the background values of the median AD (151+4 mm Hg) and was lower than the mean blood pressure in rats of the control group, 28 mm Hg (18%; p<0,05).

Along with the reduction of blood pressure medications caused tachycardia, which reached a maximum after approximately 15 minutes after drug injection. Heart rate was increased 1.4-fold (p<0.05) as compared to the initial background values and b is La above, than the heart rate in rats of the control group 1.3 times (p<0,05). Blood pressure and heart rate in control rats was not significantly changed compared with the original values (152+3 mm Hg and 313+11 beats/min, respectively). Mean BP remained depressed through the day after administration of the drug at 23±3 mm Hg (15±2%; p<0.05) as compared to the initial background values and 23 mm Hg (15%; p<0.05) as compared with rats in the control group. Signs of tachycardia in 1 day already was completely absent. The hypotensive effect of the drug lasts for 1 day and completely disappears after 4 days after its introduction.

Example 7. The study of the synthesized compounds for lowering blood pressure.

The following experiments were performed on segment perfoirmance isolated rat tail artery. Apreparatory segment of the rat tail artery, fastened one end to a cannula was placed in the working chamber, the cannula was connected with a system of internal duct and a pressure sensor for internal perfusion of the vessel and measuring perfusion pressure, respectively. Within 30 minutes, the vessel adapted to the conditions of the experiment. After 30 min began the presentation of noradrenaline (NA) in increasing concentrations (from 10-8M to 10-8M), the concentration that caused increase in perfusion pressure of 100-120 mm Hg, MF is Tali working, this solution was diluted acetylcholine (ach) and synthesized drugs. After reaching the plateau of the response IN order to verify the integrity of the vascular endothelium started perfusion OH concentration

10-8M. OH, by acting on endothelial cells of blood vessels, leads to release of nitric oxide and relaxing the vessel. Response to OH laundered the same concentration. After reaching the plateau of the reaction was started perfusion of 10-4M solution of the tested drugs, then perfesional ON and saline solution, the experiment was finished.

In the control experiments in response to the perfusion solvent-drugs - sulfoxide - no observed change in the tone of the vessel, the tested drugs in increasing concentrations caused a dose-dependent relaxation to 20% of its initial level. Evidence suggests that the drugs may act directly on the vessel, causing it to relax.

Preparations are, in particular, in the examples, obtained on the basis of the above compounds is described in the formula of the claimed invention, were tested for toxicity at a dose of from 10 to 100 mg per 1 kg of body weight in Wistar rats. In the experiment used 100 male rats weighing 240-300 grams. The drugs did not show a toxic effect and not adversely affecting animal behavior.

Research the Finance synthesized drugs on the basis of the above compounds on the reduction of blood pressure was carried out on rats with renovascular hypertension and in rats with spontaneous hypertension, line Okamoto and Aoki.

All tested drugs on the basis of the above compounds showed no toxicity in rats at a dose of 100 mg/kg and below.

All tested drugs on the basis of the above compounds are stable for a period of 24 hours or more - reduced blood pressure after a single oral administration when administered intravenously in liposomes, as in rats with renovascular hypertension "1 kidney - 1 clip in the modification Goldblatt experimental model of hypertension humans and in rats with spontaneous hypertension - line Okamoto and Aoki experimental model of hypertension person.

From the above it follows that the drugs on the basis of the proposed compounds have a prolonged antihypertensive effect with a maximum response at 2 days after injection and does not significantly affect the frequency of cardiovascular cuts.

Experiments on isolated rat tail artery showed that the antihypertensive effect of drugs may be due to direct action on the vascular wall.

Thus, the achieved technical result, namely received new derivatives of 1-alkyl-2-allylcarbamate-glycerine containing in the 2nd position of the molecule alkylcarboxylic group and with pronounced prelungirea the Noah antihypertensive activity and the way they are received.

INDUSTRIAL APPLICABILITY

The invention relates to chemistry and medicine, namely to antihypertensive tools and methods for their preparation.

Proposed new derivatives of 1-alkyl-2-allylcarbamate-glycerine containing in the 2nd position of the molecule alkylcarboxylic group and with pronounced prolonged antihypertensive activity, and the way they are received.

Compounds derived on the basis of the proposed invention can be used as an antihypertensive prolonged action, as drugs for the treatment of hypertension caused by kidney disease, and hypertension - disease, which affects up to 20% of the population, mainly in industrialized countries.

SOURCES of INFORMATION

1. Blank M.L., A. Cress, Snyder F." A new class of antihypertensive neutral lipid: 1-alkyl-2-acetyl-sn-glycerols, a precursor of platelet activating factor, "Biochemical and biophysical Research Communications, 118, No. 1, R. 344-350, 1984.

2. Blank M.L., A.A. Spector, Kaduce T.L., Lee T., Snyder F. "Metabolism of platelet activating factor (1-alkyl-2-acetyl-sn-glycero-3-phoshocholine) and 1-alkyl-2-acety-sn-glycerol by numan endothelial cells," Biochimica et Biophysica Acta, 876, p.373-378, 1986.

3. Kulikov, V.I., Museum of GI" Biological role of cell metabolites and structural analogs of platelet activating factor," Biochemistry, 61, No. 3, s-403, 1996.

4. Sezdarevich B., "Glyceride isomerizations in lipid chemistry," J.Am.Oil Chem. Soc, 44, p.381-393, 1967.

5. Van Lohuizen O.E., Varkade P.E., "Migration of the acyl group in glcerol," Rec.trav chim., 79(2), p.133-138, 1960.

6. Malrin So "The synthesis of possesses anti-inflammatory properties. Progress in the chemistry of fat and other lipids," 4, p.64-67, 1957.

7. Mattson F.H., Volpenheim R.A., "Synthesis and properties of glycerids," J. Lipid Res., 3, p.281-296, 1962.

1. A means of having antihypertensive activity, representing a 1-alkyl-2-alkylcarboxylic General formula I
,
where R is a hydrocarbon radical -(CH2)nCH3(n=10-18), R1is methyl, ethyl.

2. A method of obtaining a 1-alkyl-2-alkylcarboxylic General formula I
,
where R and R1specified in claim 1 according to which the original 1-alkylglycerol General formula II

where R is a hydrocarbon radical -(CH2)nCH3(n=10-18) is subjected to interaction with trimethylchlorosilane using triethylamine in an environment of toluene at a temperature of -20 to 0°C, then the reaction mass is added the appropriate alkilizotsyanat and treat her byflorida ammonium in the medium of methanol at room temperature.



 

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11 cl, 20 cx

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of aminomethyleneamides (Mannich bases), in particular, to synthesis of N,N'-bis-(dimethylaminomethyl)urea representing an intermediate compound used in modification of polyacrylamide and conferring to its high flocculation properties. Method is carried out by interaction of dimethylamine, formaldehyde and urea for two steps. On the first step dimethylamine aqueous solution is mixed with formaldehyde or paraform solution in the mole ratio 1:1, at temperature (+5)-(+40°C) followed by holding for 30 min. On the second step urea solution is added to prepared solution of N,N-dimethtylaminomethanol in the mole ratio urea : dimethylamine = 1:2 and held at temperature (+5)-(+50°C). Invention provides improving technology, enhancing yield and purity of the end product.

EFFECT: improved method of synthesis.

4 cl, 4 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for carbamoylation reaction of alcohol having both alcoholic moiety and basic moiety and/or sulfenyl moiety. Method involves mixing cyanate with indicated alcohol in inert solvent in anhydrous conditions, cooling formed reaction mixture to temperature from about -25°C to about 40°C, addition of acid to the cooled reaction mixture at the rate maintaining temperature lower 0°C, stirring the acid-containing reaction mixture at temperature from about -10°C to about 0°C for about 8-10 h and treatment of the reaction mixture with water. Method can be used for carbamoylation reaction of capravirine sulfenyl alcohol. Method provides enhancing conversion of alcohol and yield of carbamate.

EFFECT: improved method for carbamoylation reaction.

11 cl, 3 ex

The invention relates to the use of fluorinated derivatives of carbamino acid, namely polyfluoroankyl-N-arylcarbamates General formula

< / BR>
where R and R' = H, o-, m-or p-alkyl (C1-C3, CF3CH3S, Cl, NO2, NHCOOCHR"R"';

R" = H, CF3;

R"' = CF3, (CF2)nH, where n = 2-6, or-CF2NO2except 2.2-debtor-2-nitroethyl-N-phenylcarbamate, 2.2.2-triptorelin-N-p-nitrophenylacetate,

possessing antimicrobial activity

The invention relates to methods for obtaining concentrated urea-formaldehyde products are applicable in various industries, including as a source of concentrated formaldehyde

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of organic chemistry and pharmaceutics and deals with novel anti-hypertension salt of general formula [(R1-COO-)·(H3N-R2)], where R1 is inhibitor of angiotensin-converting enzyme, selected from group, which consists of perindoprilat, ramiprilat, spiraprilat, benazeprilat, moexiprilat, trandalaprilat, fosinoprilat, enalaprilat, zofenoprilat or lisinopril, and R2 -calcium channel blocker, selected from group, consisting of amlodipine, lacidipine, felodipine, isradipine.

EFFECT: invention ensures reduction of therapeutic doses and side effects.

3 dwg, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to amide of δ-amino-γ-hydroxy-ω-arylalcane acid of formula and its pharmaceutically acceptable salts. Also described are pharmaceutical compositions, which include said compounds, and application of said compounds for preparation of medication, intended for treatment of pathological states, associated with renin activity, in particular for treatment of hypertension.

EFFECT: obtaining pharmaceutically acceptable salts, which possess rennin-inhibiting ability.

21 cl, 161 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, particularly to therapy and pharmacology, particularly to pharmacogenetic analysis, and concerns detecting genetic polymorphisms being efficacy markers of aliskiren as an antihypertensive agent. Aliskiren is used for preparing a drug for treating hypertension, for reducing mean derived systolic pressure and for reducing diastolic pressure. And aliskiren therapy is applied in a group of patients specified by genetic polymorphisms in biomarker genes where the aliskiren efficacy is indicated by genetic polymorphisms - SNP_4769 as specified in SEQ ID NO:1 in an angiotesin-converting enzyme (ACE) gene, SNP1445 as specified in SEQ ID NO:2 in an angiotensin II receptor type 2 (AGTR2) gene, and SNP_4795 as specified in SEQ ID NO:3 in an AGTR2 gene .

EFFECT: invention provides a method for determining sensitivity of a hypertensive individual to the aliskiren therapy, and application of a gene product of a gene specified in a group including the angiotesin-converting enzyme (ACE) gene and angiotensin II receptor type 2 (AGTR2) gene as a drug target.

6 cl, 1 dwg, 7 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology, endocrinology, and can be used for normalising the blood microvesicle level in impaired glucose tolerance. That is ensured by graduated physical activity, and administration of metformin 500 mg twice a day. The therapeutic course is at least 5 weeks.

EFFECT: offered combination of therapeutic modalities enables normalising the blood microvesicle level in a relatively short time that promotes prevention of thrombotic complications in the case patients.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to gerontology, endocrinology, and can be used for pathologically raised biological age reduction in the patients with abdominal obesity. That is ensured by prescription of efficient graduated static and dynamic physical activity, daily swimming in a pool for not less than 30 minutes a day, and also administration of metformin in dosage 850 mg twice a day. The therapeutic course is 7 weeks.

EFFECT: offered combination of the modalities enables to adjust the biological and chronological ages that improves quality of life in the case patients.

2 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology, and can be used for normalisation of adenosine diphosphate and adenosine triphosphate thrombocyte secretion activity in the patients with arterial hypertension and impaired glucose tolerance. That is ensured by graduated physical activities, daily swimming in a pool for at least 20 minutes a day, and also prescribed metformin 500 mg twice a day and lisinopril 10 mg once a day in the morning.

EFFECT: combination of therapeutic modalities enables rapid normalisation of adenosine diphosphate and adenosine triphosphate thrombocyte secretion activity that promotes prevention of thrombotic complications in the case patients.

9 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology, endocrinology, and can be used for normalising the blood α2 antiplasmin concentration in arterial hypertension and impaired glucose tolerance. That is ensured by graduated physical activities, daily swimming in a pool for at least 20 minutes a day, and also prescribed metformin 500 mg twice a day and lisinopril 10 mg once a day at regular hours in the morning. The therapeutic course is 1 months.

EFFECT: offered combination of therapeutic modalities enables normalising the blood α2 antiplasmin level in a relatively short time that promotes prevention of thrombotic complications in the case patients.

1 ex

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