Combined antituberculous drugs
SUBSTANCE: agent is presented in the form of a tablet, contains isoniazid and a substance which reduces its toxicity; as the substance which reduces the isoniazid toxicity, it contains thiotriazolin. The isoniazid/thiotriazolin ratio makes 4:1.
EFFECT: combined antituberculous drug ensures reducing toxicity as compared to the known ones and increasing its pharmacological activity.
2 cl, 1 ex, 1 tbl
The invention refers to pharmaceutics and medicine, namely to Phthisiology, and can be used in the pharmaceutical industry in the manufacture of drugs for the treatment of tuberculosis.
The effectiveness of providing medical care to the population depends on the availability of highly competitive medicines, and in particular, it relates to means for the treatment of tuberculosis. Today, TB is one of the most common infectious diseases. In the treatment of tuberculosis patients is chemotherapy. Clinical efficacy of anti-TB drugs depends on many factors, important among which are the sensitivity or resistance of mycobacteria to drugs used, the level of bacteriostatic concentrations in the blood, the degree of penetration of drugs in the lesion, the ability of drugs to act on the external and intracellular (phagocytosed) mycobacteria. But not less important are also the tolerability of medicines and their safety. Chemotherapy of tuberculosis requires prolonged use of anti-TB drugs, which increases the risk of side effects, pronounced violations metabolism and functions of liver, heart, and nervous system�we etc. Side effects of anti-TB drugs is one of the main reasons for the lack of effectiveness of treatment of such patients. Originating in the process of mono - or combination chemotherapy, side effects significantly limit the possibility of purposeful influence of drugs and reduce the effectiveness of treatment of TB patients by the main indicators: timing of termination of smear and frequency of complete recovery.
In this regard, the problem of preventing the side effects of TB drugs on the human body remains relevant.
Isoniazid is one of the reference drugs main group, but he, along with positive farmacoterapeutica effect, toxic to liver, Central and peripheral nervous system, cardiovascular system and hemodynamics. It is known that isoniazid adverse reactions, pathogenetic mechanisms have not been established. Correction of adverse reactions that have occurred in the process of combination chemotherapy of tuberculosis is a priority of the national Phthisiology. There remains the issue of prevention of toxic effects of isoniazid, so one of the biggest challenges of TB is the further development of new methods of prevention and treatment�ia side effects of anti-TB drugs, and pharmaceutical chemistry and technology of drugs - development of efficient and low-toxic pharmaceuticals.
The use of antioxidants in the treatment of infectious diseases, tuberculosis including, has a definite perspective. So recently in the world practice there is a tendency for the creation of drugs on the basis of fixed combinations that contain compatible on physico-chemical and pharmacological characteristics of the antioxidant and the basic drug therapy, which produce a higher, in comparison with the application as a separate component of comprehensive treatment, therapeutic efficacy and safety.
It should be noted that the indirect mechanism of action of isoniazid is hypermodule oxygen radicals, this leads to hepato-, cardio - and embryotoxicity. Therefore, it is appropriate the use of antioxidants to reduce the toxicity of isoniazid, in this regard, in recent times considerable attention attracts clinicians, in particular, thiotriazolin, which, in addition to antioxidant action, has a wide range of pharmacological activity. Studies on laboratory animals proved the protective effect of the synthetic drug metabolitic nature of the action of thiotriazolin �ri the effect of toxic doses of isoniazid.
Thus, it is important to develop means of TB action which would have had a strong anti-TB effect and low toxicity.
Known combination remedy for tuberculosis treatment (patent RF №2406518, IPC A61K 36/28 (2006.01), A61K 31/4409 (2006.01), A61P 31/06 (2006.01). TB compositional tool // the Invention. The utility model. - 20.12.2010).
Specified contains anti-tuberculosis drug isoniazid and individual glycoside plant Stevia rebaudiana - stevioside or stationbased, or a mixture of the glycosides of the specified plants, which is a sweetener with the high ratio of components, wt.%:
|stevioside or stationbased, or a mixture of the glycosides of the plant Stevia rebaudiana - sweetener||else|
Common essential features of the claimed invention and the funds are as follows:
- the presence in the formulation of isoniazid,
- the presence in the medium of the substance, which reduces the toxicity of isoniazid.
But the above solution has some drawbacks.
One of the disadvantages of the aforementioned funds of the prototype is that glycosides, which are part of the Stevia ebaudiana, not only have antioxidant and hepatoprotective activity required to reduce the toxicity of isoniazid, but also enhance the hepatotoxicity of isoniazid.
In addition, methods of isolation and purification of glycosides of Stevia rebaudiana quite time consuming because of imperfections in technology and also require expensive equipment and reagents, most of which are toxic (chloroform, ethers, dioxane, n-butanol, and so forth). In addition, when using these reagents, it is assumed the existence of complex waste management systems, special equipment and devices. Not always complete extraction of glycosides from raw materials.
The tool prototype is used in powder form, the use of which is not sufficiently comfortable for the patients.
The basis of the invention tasked with improving combined anti-TB drugs by introducing in its composition other active substances which reduce the toxicity of isoniazid, which has a more broad spectrum, and has a stronger activity that will reduce the toxicity of funds in comparison with known and increasing its pharmacological activity.
The problem is solved in that in the combined anti-TB medication to�e contains isoniazid and substance reduce its toxicity, what is new is that the product is in tablet form and as a substance that reduces the toxicity of isoniazid, contains thiotriazolin. The ratio of isoniazid and thiotriazoline is 4:1.
A causal relationship between the totality of the claimed features and the technical result is the following.
Recently actively developed medicines in the form of fixed combinations, which contain compatible on physico-chemical and pharmacological characteristics of the antioxidant and the basic drug therapy. The presence of antioxidant in products such defines significantly higher in comparison with the application as a separate component of comprehensive treatment, therapeutic efficacy and safety of such funds.
In the available literature, we did not find descriptions of complex solid dosage forms with isoniazid, which would contain an antioxidant.
It is known that isoniazid is a rather toxic drug and has a number of serious side effects, such as those focused on breaking the delicate parts of metabolism of neurocytes, cardionet and hepatocytes; isoniazid exhibits neuron-, cardio-, hemato - and hepatotoxicity. So, isoniazid affects the cardiovascular, n�rvnoy and hepato-biliary system and the hematopoietic system. The introduction of thiotriazolin in the product with isoniazid significantly reduces the negative toxic effects of the Central nervous system, cardiovascular, under own trade mark system and on the blood and thereby increases the safety of the treatment of tuberculosis. A similar effect takes place because thiotriazolin has strong oxidative properties, reduces the overproduction of superexcitation and peroxynitrite, prevents oxidative modification of protein structures of receptors, ion channels, enzymes, transcription factors, activates antioxidant system enzymes. Thiotriazolin has also metabolitic action aimed at the preservation of oxidative energy production, reducing the severity of mitochondrial dysfunction and apoptosis. Thiotriazolin is a powerful hepatoprotector. Metabolitic and hepatoprotective properties of thiotriazolin provide a significant reduction of negative influence of isoniazid on the human body. The proposed fixed dose combination of isoniazid and thiotriazoline provides significant security improvements in the treatment of tuberculosis.
In our experiments, it was found that the optimal ratio of isoniazid and thiotriazoline in the proposed measure is the ratio of 4:1.
R�the results of our research, presented in the table below, indicate that the introduction of thiotriazolin in the composition of tablets with isoniazid leads to a significant reduction of acute toxicity of isoniazid.
So, the value of LD50isoniazid the determination method of Kerber is 1500±347 mg/kg after intragastric administration white outbred rats weighing 140-160 grams. The introduction of thiotriazolin in the composition of tablets with isoniazid leads to lower acute toxicity of isoniazid in 2.67 times (LD50of isoniazid in tablets with thiotriazolin is 4014,6±165 mg/kg after intragastric administration).
|Rates of acute toxicity of isoniazid and fixed combination of isoniazid with thiotriazolin after a single injection (M±M)|
|Groups of animals||The ratio of the mass of the heart||The ratio of the mass of the liver||The ratio of the mass of the brain||LD50mg/kg|
|Intact animals (n=6)||18,1±0,61||1,95±0,09||22,1±1,38||-|
|Animals that received isoniazid (n=6)||22,7±0,53||3,77±0,45*||28,9±3,41*||1500±347|
|Animals that received isoniazid + titerator (n=6)||17,9±1,251||2,17±0,651||21,8±3,751||6691±275 (in terms of pure isoniazid - 4014,6±165)|
|* - p≤0,05 relative to the group of intact animals;|
|1-p≤0.05 relative to the group of animals which received only isoniazid|
LD50a combined preparation of isoniazid with thiotriazolin in the form of tablets is 6691±275 mg/kg.
When studying the toxicity of isoniazid was found that the drug exhibits expressed hepato-, neuro - and cardiotoxicity, increasing the ratio of the mass (Km) liver 93%, of the brain is at 31% and 25%. Drug fixed dose combination of isoniazid with thiotriazolin is not hepato-, neuro - and ka�detoxacai after a single dose. The coefficients of the mass of the liver, brain and heart of animals which received the tablets of isoniazid with thiotriazolin, are within the physiological norm, and they are lower than in the group of animals which received only isoniazid, 42%, 24% and 21%, respectively.
Thus, the introduction of thiotriazolin in the composition of anti-tuberculosis drugs containing isoniazid, decreasing the overall and neuro-, cardio - and hepatotoxicity latter, unlike the prototype, where only decreases cardiotoxicity funds.
Pills, depending on the clinical purpose (prevention of relapses of tuberculosis, treatment of active forms, for children and the like) can be manufactured with different content of active substances, while maintaining the claimed ratio of isoniazid with thiotriazolin 4:1.
For example, it can be tablets containing isoniazid 100 mg and thiotriazolin 25 mg, or 200 mg and 50 mg, or 400 mg and 100 mg, or 600 mg and 150 mg, respectively.
Pills that contain isoniazid and thiotriazolin, is made by obtaining a powdery mixture of active ingredients isoniazid and thiotriazoline with the addition of a sufficient amount of excipients and subsequent pressing. The composition of the tablets include various excipients, for example polyfunctional auxiliary prophetic�TWA, fillers, disintegrants, anti-friction substance.
Preformed tool, which States, fully meet pharmacopoeial requirements. Thanks to its antioxidant thiotriazolin obtained preformed tool provides a significant reduction of the toxicity of isoniazid and better pharmacological properties of the integrated product compared to the vehicle-prototype and can be proposed for the industrial production of anti-TB drugs.
1. Combined anti-tuberculosis drug containing isoniazid and substance to reduce its toxicity, characterized in that the product is in tablet form and as a substance that reduces the toxicity of isoniazid, contains thiotriazolin.
2. Combined anti-TB drug according to claim 1, characterized in that the ratio of isoniazid and thiotriazoline is 4:1.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a chemical compound of formula wherein R=benzyl and to an antituberculous therapeutic agent representing a composition of imidazo[1,2-b][1,2,4,5]tetrazine derivative of formula I, wherein R=benzyl, isopropyl or phenyl and the known antituberculous preparation pyrazinamide with the ingredients in mole ratio 1:1.
EFFECT: there are prepared new antituberculous therapeutic agents.
2 cl, 2 tbl, 6 ex
SUBSTANCE: invention relates to organic chemistry and specifically to nitroimidazooxazine derivatives of general formula I, where n equals 1, V and W independently denote H or CH3, and one of X and Y is H and the other is one of the formulae and , where formula IIa includes a single ring labelled at position 3 and position 4 and containing R1 as a substitute, and formula IIb includes a first ring labelled at position 3 and position 4 and containing as substitutes both R2 and a terminal ring, labelled at position 4 and containing R1 as a substitute, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb include C, CH, or N at each ring position, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb independently contain no more than two nitrogen atoms; Z in formulae IIa and IIb is CH2 or a direct bond, R1 is independently any one or two of H, F, C1, CF3, OCF3 or OCH2Ph, and R2 is H. The invention also relates to a pharmaceutical composition based on the compound of formula I, a method of preventing and treating a microbial infection based on use of the compound of formula , and specific nitroimidazooxazine derivatives.
EFFECT: obtaining novel compounds with useful biological activity.
7 cl, 21 dwg, 3 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of genetic engineering, molecular biology and vaccinology. Claimed is polyepitopic anti-tuberculosis vaccine construction for formation of immune response, which provides induction of immune response of CD8+ T-lymphocytes, consisting of universal polyepitopic immunogen, containing CTL-epitopes, selected from immunodominant antigens of M. tuberculosis, fused from N-end with ubiquitin, and having amino acid sequence SEQ ID NO: 1.
EFFECT: vaccine construction provides achievement of effective therapeutic T-cell immune response not only due to antigenspecific cytotoxic CD8+ T-lymphocytes but also intensive response of CD4+ T-lymphocytes.
1 tbl, 11 dwg
SUBSTANCE: invention concerns Mycobacterium tuberculosis growth inhibitors representing (+) and (-)-enantiomers of derivatives of usnic acid containing a furilidene furanone fragment, namely (10R,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4a and (10S,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4b
EFFECT: inhibitors possess the high antimicrobial activity.
2 tbl, 7 ex
SUBSTANCE: invention relates to novel derivatives of 1-(2-chloroquinolin-3-yl)-4-dimethylamino-2-(naphthalen-1-yl)-1-phenylbutan-2-ol of general formula I or their pharmaceutically acceptable salts with acids, where R1 denotes H, R2+R3 denotes -O-(CH2)n-O-, where n=1-2, which forms additional dioxane and 1,3-dioxolane rings. The invention also relates to a method of producing a compound of formula I and to use of the compound of formula I in treating infectious mycobacterial diseases.
EFFECT: obtaining novel compounds with useful biological activity.
4 cl, 2 tbl, 3 ex
SUBSTANCE: for treatment of patients with pulmonary tuberculosis with accompanying non-specific bronchitis at the background of carrying out standard anti-tuberculosis therapy from the first day of treatment additionally daily for 3 months the preparation Wobenzym is introduced in a dose of 1 tablet 2 times per day, 30 minutes before meal, and inhalation with a solution of the preparation Hixozide in a dose of 350 mg in 10 ml of water for injections is performed 2 times per week, the course constitutes 24 procedures.
EFFECT: method makes it possible to increase treatment efficiency by indices of infiltration resorption, closing of the decay cavities and abacillation.
1 tbl, 2 ex
SUBSTANCE: for complex therapy of the first time identified pulmonary tuberculosis traditional anti-tuberculosis therapy is carried out. After two weeks of anti-tuberculosis chemotherapy, complex physiotherapy is performed. In the morning 40-60 minutes after meal ultrasound inhalation with an inhibitor of proteases contrykal in a dose of 5000 UNITS, diluted in 3-4 ml of an isotonic solution of sodium chloride is carried out. Inhalation is carried out at a temperature of the solution of 35°C for 10 minutes on the apparatus "Vulkan-1". 20 minutes after inhalation magnetic infrared laser therapy (MIL-therapy) is performed from the apparatus "Rikta-04/4" on affected zones of the lungs by contact method of the application of the apparatus emitter. Frequency of the laser impact constitutes 5-50 Hz. Average power of infrared light-diode radiation is 60±30 mW, an impact with constant magnetic field is realised with induction 35±10 mT for 1-5 min. The course of treatment constitutes 30-40 daily procedures as well.
EFFECT: enhancement of infiltration resorption, closing decay cavities in the shorter period, arrest of intoxication symptoms by the end of the first month of treatment, reduction of terms of elimination of clinical and laboratory manifestations of tuberculosis.
3 cl, 2 ex
SUBSTANCE: drug preparation for treating tuberculosis contains an active substance isoniaside, and a pharmaceutical carrier tiozol gel with the isoniaside concentration of 5.7-54.5 wt % and the tiozol gel concentration of 45.5-94.3 wt %.
EFFECT: higher clinical effectiveness in tuberculosis and lower toxicity.
2 cl, 2 tbl
SUBSTANCE: claimed is a cocrystalline form of fenbufen with pyrazinamide, where molar ratio of fenbufen with pyrazinamide constitutes 1:1, which has an endothermal peak from 148 to 152°C by the data of measurements by means of differential scanning calorimetry and peaks at 2θ(°) 7.38, 10.43, 11.04, 21.67 by the data of measurement of polycrystal X-ray radiation diffraction.
EFFECT: increased rate and level of solubility of the crystalline form of fenbufen and its suitability for application in the pharmaceutical industry.
2 ex, 7 dwg
SUBSTANCE: with underlying antituberculous therapy from the first day of treatment, a therapeutic course is added with an oral administration of preparations Wobenzym and Thiotriazoline; Wobenzym is administered for 4 months in a dose of 1 tablet once a day 30 minutes before breakfast, while Thiotriazoline is administered for the first 15 days in a dose of 100 mg 2 times a day, from the 16th to 45th day in a dose of 100 mg 1 time a day, on the 46th day, Thiotriazoline is withdrawn.
EFFECT: method enables higher clinical effectiveness and reduced rate of an adverse hepatotoxic response to the antituberculous preparations due to improving the immune status and peroxidation values.
6 tbl, 2 ex
SUBSTANCE: invention represents a pharmaceutical composition for treating the HIV infection in the form of a solid dosage form, containing at least one HIV protease inhibitor in a therapeutically effective amount specified in a group of nelfinavir, sacvinavir, tipranavir, darunavir, indinavir, ritonavir, lopinavir, palinavir or fosamprenavir, and pharmaceutically acceptable additives differing by the fact that as the pharmaceutically acceptable additives it contains at least one water-insoluble polymer from 0.39 to 28 wt % of the total dosage form, surfactants, excipients up to 100% of the total dosage form, as well as a method of treating the HIV infection.
EFFECT: pharmaceutical composition according to the invention possesses the improved technological properties and improved bioavailability as compared to a prototype therapeutic agent.
10 cl, 4 ex, 1 tbl
SUBSTANCE: invention refers to medicine, gynaecology, birth control techniques used as and when necessary, and emergency contraception. Ulipristal acetate or its metabolite is administered orally in a female no more than 72 hours to 120 hours after a sexual encounter in a dose of 20 to 30 mg. Another dose can be administered again at least twice a month. The preparation can be administered either in the form of an immediate-release dosage form, in the form of a tablet.
EFFECT: method provides the high efficacy of emergency contraception even in low doses and late administration of the preparation - up to 120 hours after the sexual encounter as compared to a reference preparation of levonorgestrel.
SUBSTANCE: presented is a group of inventions containing a solid dosage composition and a method for producing it. The solid dosage composition contains at least one pressed layer containing ibuprofen, microcrystalline cellulose and hydroxypropyl methylcellulose (HPMC) K100LV, HPMC K4M and combinations thereof, wherein HPMC is present in an amount of 10 to 30 wt % of the pressed layer, wherein viscosity of 2 wt/wt % of K100LV, HPMC K4M and a combination thereof makes 100 to 1414 sP, and wherein ibuprofen is subject to wet granulation. The method for producing the above composition involves pre-mixing ibuprofen by wet granulation with the above ingredients.
EFFECT: minimising the immediate release of ibuprofen ensured by producing the more stable gel matrix.
3 cl, 9 dwg, 2 tbl, 24 ex
SUBSTANCE: coagglomerates of crystalline mannitol and granular starch in the ratio mannitol/starch from 99.5/0.5 to 50/50 have compressibility of 200 N to 450 N, flow time of 3 to 15 s and volume mean diameter D4.3 of particles based on laser granulometry of 60 to 500 mcm. The coagglomerates are intended for producing tablets or solid gelatin capsules for use in pharmaceutics. The method of producing said coagglomerates includes preparing, at 45-65°C, a solution of mannitol and granular starch or a mannitol solution only, where content of solid substance ranges from 25% to 45%, holding said solution at 45-65°C, spray-drying said solution in an MSD-type dryer equipped with a high pressure spray-drying nozzle with recycling of the fine particles at the spray-dryer top and, if necessary, adding dry starch, separating the obtained the coagglomerates of mannitol and of starch. The method can also include granulating the solution of mannitol and starch by spraying in a circular continuous fluidised-bed granulator with a discharge pipe or plug-flow rectangular continuous fluidised-bed granulator.
EFFECT: obtaining coagglomerates with good compressibility and good fluidity.
9 cl, 12 tbl, 8 ex
SUBSTANCE: drug preparation contains a combination of phenylephrine hydrochloride (or an equivalent amount of the other pharmaceutically acceptable form of phenylephrine) and paracetamol.
EFFECT: combining two active ingredients provides effective relief of cold and influenza symptoms.
14 cl, 5 dwg, 4 ex, 10 tbl
SUBSTANCE: agent in the form of a vitamin complex applicable for replenishment of the deficiency of various nutrients in the body and in diseases related to the deficiency, as well as to prevent nausea and vomiting in the form of tablets exhibiting the therapeutic effect on nausea and vomiting of pregnancy, characterised by the fact that it contains ginger (Zingiber officinalis) in the form of dry extract of roots, folic acid, Vitamin B6, a pharmacologically acceptable calcium source and additives - sorbitol, magnesium stearate and silicon dioxide. What is also presented is a method for preparing it by granulating and drying in the certain environment and pressed.
EFFECT: agent represents the effective, easy-to-use vitamin additive with the therapeutic effect, which has the safe length of administration.
5 cl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics and represents a controlled-release aceclofenac preparation for oral administration once a day, exhibiting the fast analgesic and anti-inflammatory action, containing a fast-release layer containing aceclofenac, a solubiliser, a water-soluble additive, a disintegrating agent, a vehicle and a fast-acting additive, as well as a sustained-release layer containing aceclofenac, a solubiliser and a release control base consisting of mixture of hydroxypropyl methyl cellulose (HPMC) with a viscosity of 80,000 sP to 120,000 sP and carbomer taken in mass ratio 7:1 to 9:1.
EFFECT: invention provides a sequential and uniform dissolution rate and a controlled release of the active agent.
7 cl, 12 tbl, 11 dwg, 10 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine and represents a prolonged-release pharmaceutical composition containing entacapone, consisting of an immediate-release layer and a prolonged-release layer.
EFFECT: composition provides the prolonged release of the therapeutic agent, its uniform blood plasma concentration and lower rate of composition intake.
11 cl, 11 ex, 23 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, chemical-pharmaceutical industry and concerns agents possessing the nootropic and neuromodulatory activity. A tabletted pharmaceutical composition possessingthe nootropic and neuromodulatory activity, characterised by the fact that as an active substance, it contains N-cabamoylmethyl-4-phenyl-2-pyrrolidone; the additives are lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, colloidal silicon dioxide (aerosil) and calcium stearate. The tablets of the composition are prepared by direct compression.
EFFECT: produced preparation has a lower variability of the pharmacological action.
3 cl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, and concerns a pharmaceutical composition for treating gastroduodenal ulcer in the form of tablets, capsules or gel, containing therapeutic agents and a consistency base applicable for each dosage, wherein the therapeutic agents are as follows: recombinant interferon specified in a group: recombinant interferon alpha, recombinant interferon beta, recombinant interferon gamma; antiseptics; amino acids specified in a group: arginine, histidine, lysine, cysteine, methionine, glutamic acid; and antioxidants specified in a group: beta-carotene, vitamin C, vitamin E.
EFFECT: invention has the integrated body effect promoting faster healing of the mucosal defect accompanying the aggravated gastroduodenal ulcer and preventing recurrences, including by the eradication effect.
6 cl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to compound of formula (I) , where A is selected from -C(=O)-, -S(=O)2-, and -P(=O)(R5)-, where R5 is selected from C1-6-alkyl, C1-6-alkoxy and hydroxy; B is selected from single bond, -O-, and -C(=O)-NR6-, where R6 is selected from hydrogen; D is selected from single bond, -O-, and -NR9, where R7, R8 and R9 are independently selected from hydrogen; m equals integer number 0-12 and n equals integer number 0-12, where the sum m+n equals 1-20; p equals integer number 0-2; R1 is selected from optionally substituted heteroaryl, where heteroaryl represents aromatic carbocyclic ring, where one carbon atom is substituted with heteroatom; R2 is selected from hydrogen, optionally substituted C1-12-alkyl, and substituents are selected from phenyl, morpholine, halogen and pyridine; C3-12-cycloalkyl, -[CH2CH2O]1-10-C1-6-alkyl); and R3 is selected from optionally substituted C1-12-alkyl, and substituents are selected from morpholine, phenyl, dialkylamine and C3-12-cycloalkyl, optionally substituted with halogen aryl; or R2 and R3 together with adjacent atoms form optionally substituted with alkylcarbonyl or alkyl N-containing heterocyclic or heteroaromatic ring; each of R4 and R4* independently represents hydrogen; and their pharmaceutically acceptable salts, as well as to application of said compounds for treatment of diseases/states, induced by increased level of nicotinamide phosphoribosyltransferase (NAmPRTase).
EFFECT: obtaining novel compounds.
21 cl, 1 dwg, 2 tbl, 83 ex