N-(2-benzothiazolyl)amide 2-hydroxy-4-oxo-4-(4-chlorophenyl)-2-butenoic acid having antimicrobial and anti-inflammatory activity
SUBSTANCE: invention relates to N-(2-benzothiazolyl)amide 2-hydroxy-4-oxo-4-(4-chlorophenyl)-2-butenoic acid of formula: , which has antimicrobial and anti-inflammatory activity along with low toxicity.
EFFECT: obtaining a compound which can be used to treat diseases associated with pathogenic microorganisms and inflammation.
1 cl, 2 tbl, 1 ex
The invention relates to the field of organic chemistry, new biologically active substances of class N-heterylamides 4-aryl-2,4-dioxobutane acids, namely N-(2-benzothiazolyl)amide 2-hydroxy-4-oxo-4-(4-chlorophenyl)-2-butenova acid (1) formula
possessing antimicrobial and anti-inflammatory activity, suggesting its use in medicine as a medicinal antimicrobial and anti-inflammatory agents. The closest analogue to the structure and action of the present compound is N-(2-thiazolyl)amide and 2-hydroxy-4-oxo-4-(4-chlorophenyl)-2-butenova acid (2) [andrejchikov US, Milutin A.V., I. Krylov, etc. Synthesis and biological activity of heterylamides aroylpropionic and 5-arylpyrazole-3-carboxylic acid // Chem.-Pharm. Journe. - 1990. No. 7. - Pp.33-35]
Structural analogue of 2 does not possess anti-inflammatory activity. Data on antimicrobial activity of the structural analogue of 2 in the literature are missing.
The standards of comparison are the following:
1) an antimicrobial agent chlorhexidine [1,6-di-(4-chlorophenylurea)-hexane] (3)widely used in medical practice and are similar in action [Mashkovsky PPM Medicines. - 15-ed., Rev., Corr. and extra - M.: OOO "Publishing The New wave", 2005. - S-936];
2) anti-inflammatory drug diclofenac (sodium salt of 2-[(2,6-dichlorophenyl)amino]phenylacetic acid) (4)widely used in medical practice and are similar in action [Mashkovsky PPM Medicines. - 15-ed., Rev., Corr. and extra - M.: OOO "Publishing house New wave", 2005. - S].
Object of the invention is the finding in a series of N-heterylamides 4-aryl-2,4-dioxobutane acid substances with strong antimicrobial and anti-inflammatory activity and low toxicity.
This object is achieved by obtaining N-(2-benzothiazolyl)amide 2-hydroxy-4-oxo-4-(4-chlorophenyl)-2-butenova acid (1), which has antimicrobial and anti-inflammatory activity.
The claimed compound 1 synthesized by the interaction of 5-(4-chlorophenyl)-2,3-dihydrofuran-2,3-dione with 2-aminobenzothiazole at equimolar ratio of reactants in the medium of anhydrous chloroform at room temperature, followed by separation of the target product with known methods using the pattern
Example 1 to obtain compound 1. To a solution of 2.09 g (0.01 mol) of 5-(4-chlorophenyl)-2,3-dihydrofuran-2,3-dione in 30 ml of anhydrous chloroform is added a solution of 1.50 g (0.01 mol) of 2-aminobenzothiazole in 20 ml of anhydrous chloroform, incubated at room temperature for 24 hours. The reaction mixture is cooled is about 0°C, the precipitation is filtered off, recrystallized from toluene and dried. Yield 3.4 g (95%). TPL 210-212°C. Found, %: C 57.08; N, 3.12; N, 7.92. C17H11ClN2O3S. Calculated, %: C 56.91; N, 3.09; N, 7.81.
IR-spectrum (Specord M80, liquid paraffin, v, cm-1): 3280 (NH), 1710 (CONH), 1640, 1610 (C4=O, C=C, C=N). An NMR spectrum1N (Bruker DRX 500, DMSO-d6, GMDS, δ, ppm): 7.22 (1H, CH), 7.33-7.99 m (10H,6H5With6H4) NH).
The claimed compound 1 is a yellow crystalline substance, soluble in toluene, dioxane, dimethylsulfoxide, and insoluble in water and alkanes.
Determination of the bacteriostatic activity was performed by the method of twofold serial dilutions in liquid nutrient medium [Manual on experimental (preclinical) study of new pharmacological substances / Fisenko VP (as amended). - M.: JJA Remedium, 2000. - S-273]. For all the studied compounds were determined IPC in respect of pharmacopoeial strains: S.aureus was ATSS 6538-P and E.coli was ATSS 25922. The results of the tests are presented in table 1. Crops produced in mesopotania broth, pH 7.0 with different concentrations of the tested compounds. The cultures were grown in test tubes on a beveled apparitional environment (mastopathy agar). To determine the antimicrobial activity was used 18-20-hour culture. For preparation of the working ot the art of microbes produced washout grown culture isotonic sodium chloride solution, and set the density of the microbial suspension according to the turbidity standard 5 units. Next, from the obtained microbial suspension (500 million M.L./ml) were prepared working solution of bacteria with a concentration of 5 million M.L./ml of This suspension of microbes was made in the amount of 0.1 ml in tubes with serial dilutions of study drug. Thus, microbial load when determining the ACA was 250000 M.L./ml of the Studied compound in the amount of 0.05 g was dissolved in 5 ml of dimethylformamide and 1 ml of the prepared dilution of 1:100 was combined with 4 ml mycopathologia broth (1:500). Next was preparing a series of serial dilutions of the compounds twice with decreasing concentration. Records of the results produced after 18-20 hours of exposure control and experimental tubes in the incubator at 37°C. the Minimum inhibitory concentration (MIC) was determined by the absence of signs of growth on nutrient medium: the last tube of stunting (clear broth) corresponds to the IPC of the drug in relation to this strain. Bacteriostatic effect of the studied compounds was compared with the action of chlorhexidine.
Anti-inflammatory activity was studied in experiments on 30 outbred rats of both sexes weighing 220-260 g Compound 1 was administered orally at a dose of 50 mg/kg as a suspension in 2% starch solution for an hour before modeling acute carragenine inflammation. Carrageenophyte swelling caused subplantar injection of 0.1 ml of 1% solution Flo is ogena in hind paw of the rat. About anti-inflammatory activity was assessed by the change in the severity of inflammation in the dynamics, which were recorded ecometrics after 1, 3 and 5 hours after modeling inflammation [Methodical recommendations for a pilot study of non-steroidal anti-inflammatory chemical/ Pharmacological Committee of Ministry of health USSR, Protocol No. 22 dated 11 November 1982. - Moscow, 1982. - 47 S.]. Control animals were injected equiano amount of 2% starch solution. Drug comparison served diclofenac at a dose of 10 mg/kg the Results were processed statistically using Excel 2003 and are presented in table 2.
Acute toxicity (LD50) the claimed compound 1 was determined on 24 outbred mice of both sexes weighing 18-22 g oral route of administration as a suspension in 2% starch solution on an Express method Webprotector [Prozorovsky V.B. have been, Prozorovsky BTW, Demchenko V.M. rapid method for determination of the average effective dose and its errors. // Pharmacology and toxicology. - 1978. No. 4. - S-502]. Found that LD50connection 1 is 5800 mg/kg According to the classification of the toxicity of preparations of compound 1 belongs to the class of practically non-toxic substances [Izmerov IVAN, Sanotski I., Sidorov, K.K. Settings toxicometric industrial poisons. - M.: Medicine, 1977. - S-197]. It is 1.45 times less toxic than large Sedin, and 7,44 times less toxic than diclofenac.
|Antimicrobial activity and acute toxicity of compounds 1|
|St.aureus||E. coli||St.aureus||E. coli|
As can be seen from table 1, compound 1 exceeds antimicrobial activity of chlorhexidine against Golden staph in 62.5 times and to Escherichia coli - 32 times. The ratio of MBC (μg/ml) toxicity LD50(mg/kg) compound 1 is for Staphylococcus 0,0003 and for Escherichia coli 0,0007, while the chlorhexidine is minute rates are significantly inferior.
|Anti-inflammatory activity and acute toxicity of compounds 1|
|Connection||Dose, mg/kg||LD50mg/kg||% inhibition carragenine edema|
|1 hour||3 hours||5 hours|
|1, compared with control; 2 - compared with diclofenac.|
As can be seen from table 2, compound 1 showed a pronounced anti-inflammatory activity throughout the observation period, and at the peak of inflammation, it is not inferior to diclofenac. It should be noted that the effective dose of diclofenac is 0,013 from his LD50and the claimed compounds 0,008 from his LD50, indicating that certain advantages of the connection 1 before diclofenac in terms of its safety and effectiveness.
Thus, N-(2-benzothiazolyl)amide and 2-hydroxy-4-oxo-4-(4-chlorophenyl)-2-butenova acid (1) has higher antimicrobial and anti-inflammatory activity in comparison with the structural analogue and standards of comparison, and is practically non-toxic, which makes it possible to use it to create new medicines, which have antimicrobial and anti-inflammatory activity.
1. Andrejchikov US, Milutin AV, Krylova, I. V. and other Synthesis and biological activity of heterylamides aroylpropionic and 5-arylpyrazole-3-carboxylic acid // Chem.-Pharm. Journe. - 1990. No. 7. - Pp.33-35.
2. Mashkovsky PPM Medicines.- 15th ed., Rev., COI is. and extra - M.: OOO "Publishing house New wave", 2005. - S, 935-936.
3. Manual on experimental (preclinical) study of new pharmacological substances / Fisenko VP (as amended). - M.: JJA Remedium. - 2000. - S-273.
4. Methodological guidelines for experimental study of non-steroidal anti-inflammatory chemical / Pharmacological Committee of Ministry of health USSR, Protocol No. 22 dated 11 November 1982. - Moscow, 1982. - 47 S.
5. Prozorovskiy V.B. have been, Prozorovsky BTW, Demchenko V.M. rapid method for determination of the average effective dose and its errors. // Pharmacology and toxicology. - 1978. No. 4. - S-502.
6. Izmerov IVAN, Sanotski I., Sidorov, K.K. Settings toxicometric industrial poisons. - M.: Medicine, 1977. - S-197.
N-(2-Benzothiazolyl)amide and 2-hydroxy-4-oxo-4-(4-chlorophenyl)-2-butenova acid formula
possessing antimicrobial and anti-inflammatory activity.
FIELD: medicine, pharmaceutics.
SUBSTANCE: there is described a compound of formula I: or its pharmaceutically acceptable salt, where R2 represents (CR3R4)n-NR5R6 and m, p, q, Ar, R1, R3, R4, R5 and R6 are those as specified in the patent claim and defined as selective 5-NT6 and/or 5-NT2A antagonists. There is also described a pharmaceutical composition containing this compound, and application thereof in preparing drugs for treating diseased conditions of central nervous system chosen from psychoses, schizophrenia, manic depressions, neural disorders, memory impairment, attention deficient syndrome, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, malnutrition and Huntington's disease.
EFFECT: preparation of the compounds which can find application in treatment of a diseased condition of central nervous system.
27 cl, 1 tbl, 29 ex
SUBSTANCE: invention relates to novel compounds of general formula
, where R1 is a
or or or group, R2 is morpholine or OR' or N(R")2; R' is a lower alkyl, a lower alkyl substituted with a halogen, or -(CH2)n-cycloalkyl; R" is a lower alkyl; R is NO2 or SO2R'; R4 is hydrogen, hydroxy, halogen, NO2, lower alkoxy, SO2R' or C(O)OR"; R5/R6/R7 denote hydrogen, halogen, lower alkyl; X'/X1 denote CH or N, provided that X1 /X1' are not CH at the same time; X2 is O or S; n equals 0 or 1, and to their pharmaceutically active acid-addition salts. The invention also relates to a drug.
EFFECT: obtaining novel biologically active compounds which are active as glycine transporter 1 inhibitors.
11 cl, 24 ex, 1 tbl
SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.
EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.
21 cl, 1 dwg, 608 ex, 1 tbl
FIELD: chemistry; medicine.
SUBSTANCE: invention relates to 3-phenylpropionic acid derivatives of formula (I) as ligand of peroxisome proliferator-activated gamma-receptor (PPARγ), to their pharmaceutically acceptable salts, as well as to their application, treatment method and based on them pharmaceutical composition. Compounds can be applied for treatment and prevention of diseases mediated by peroxisome proliferator-activated gamma-receptor (PPARγ), for instance type 2 diabetes, insulin-resistance, metabolic syndrome, complications resulting from or connected with diabetes, cardio-vascular dysfunctions, atherosclerosis, obesity, cognition disturbances and lipid metabolism derangements. In general formula (I): W represents COOH or -COO-C1 - C4-alkyl group; Y represents NH; Z represents S or O; X represents O; R1 - R8 each independently represents hydrogen atom or halogen atom; A represents mono-, bi- or tri-cyclic 5-13-member heteroaryl with 1 or 2 heteroatoms selected from N, S or O, aryl, selected from phenyl and naphtyl, or -N(C1-C4-alkyl)-CO-C3-C7-cycloalkyl, where heteroaryl is optionally substituted with 1-3 substituents, independently selected from group, consisting of C1-C4-alkyl, CN, phenyl halogen and phenyl, optionally substituted with 1-3 substituents, independently selected from C1-C4alkoxy, halogen and ethylenedioxy-group; and n represents integer number from 0 to 3 including; and their pharmaceutically acceptable salts.
EFFECT: increased efficiency of composition and treatment method.
20 cl, 14 dwg, 10 ex
SUBSTANCE: invention refers to new compounds of formula (I) and its pharmaceutically acceptable salts and esters. Compounds of the present invention are characterised with properties of DGAT-1 inhibitor. In general formula (I) , Q represents O, S or NR5; A represents a linker chosen from where p is equal to 1 or 2, and , where m is equal to 0, and n is equal to 1, 2, 3 or 4, or m is equal to 1, while n is equal to 1, 2 or 3, where specified linker is optionally substituted with one or two groups R8; R1 and R2 are independently chosen from hydrogen, haloid; R3 is chosen from hydrogen, (C1-C6)alkyl optionally substituted with hydroxyl and phenyl optionally substituted with haloid; R4 is chosen from hydrogen, nitro and (C1-C6)alkyl; or R3 and R4 together with carbon atoms whereto attached, can form benzene ring optionally substituted with 1-2 substitutes. The invention also concerns compounds of formula (Ia) and (Ib) with structural formulas presented in the patent claim, and also to a pharmaceutical composition, a medical product, to application of compounds for making a medical product and compound process.
EFFECT: new compounds possess useful biological activity.
19 cl, 2 tbl, 7 dwg, 215 ex
SUBSTANCE: invention concerns benzothiazole derivatives of general formula (I) and their pharmaceutically acceptable salts as adenosine receptor ligands and based medicinal product. Compounds can be applied in treatment and prevention of diseases mediated by A2A adenosine receptors, such as Alzheimer's disease, some depressive states, toxicomania, Parkinson's disease. In the general formula (I) , R1 is C5-C6-cycloalkyl substituted by CF3 group, lower alkyl, -(CH2)nOH or -(CH2)n-O- lower alkyl, or is 1-bicyclo[2,2,1]hept-2-yl, 1-(7-oxa-bicyclo[2,2,1]hept-2-yl, 1-(5-exo-hydroxybicyclo[2,2,1]hept-2-exo-yl, 1-(5-exo-hydroxybicyclo[2,2,1]hepto-2-endo-yl, or is 1-adamantane-1-yl; R2 is lower alkyl; or R1 and R2 together with N atom form 8-oxa-3-aza-bicyclo[3,2,1]octane group, n is 0 or 1.
EFFECT: improved efficiency of treatment.
9 cl, 2 dwg, 15 ex
SUBSTANCE: invention concerns benzothiazole derivatives of general formula (1) and their pharmaceutically acceptable acid-additive salts as adenosine receptor ligands with high affinity to A2A adenosine receptor, and based medicine. Compounds can be applied in treatment and prevention of diseases mediated by A2A adenosine receptors, such as Alzheimer's disease, some depressive states, toxicomania, Parkinson's disease. In general formula (I) , R is C5-C6-cycloalkyl non-substituted or substituted by hydroxy group, or is ethyl or isobutyl, or is tetrahydropyrane-4-yl or -(CH2)n-tetrahydrofurane-2 or 3-yl or is 5-hydroxybicyclo[2,2,1]hept-2-yl; X is CH or N; n is 0 or 1.
EFFECT: enhanced efficiency of composition and treatment method.
12 cl, 2 dwg, 14 ex
SUBSTANCE: this invention refers to new compounds of formula (Ia) and to their pharmaceutically acceptable salts. Compounds of this invention are characterised by CB1 receptor antagonist properties. In formula (Ia) , R1 means phenyl independently mono-, di- or tri-substituted with haloid, (lower)alkoxy, (lower)alkyl, halogenated (lower)alkoxy or di(lower)alkylamino; R2 means phenyl, independently mono-, di- or tri-substituted with haloid, halogenated (lower)alkyl, nitro or cyano; R3 means hydrogen, nitro, amino, -NHSO2-R3a or -NHCO-R3b; R3a means (lower)alkyl, di(lower)alkylamino, benzyl, phenyl or phenyl monosubstituted with (lower)alkyl; R3b means benzyl or phenyl monosubstituted with (lower)alkyl.
EFFECT: application of compounds thereof as therapeutically active substance with CB1 receptor agonist properties and to relevant pharmaceutical composition.
18 cl, 1 dwg, 5 tbl, 70 ex
SUBSTANCE: invention relates to compounds of general formula II as neuropeptide FF receptor antagonist, their pharmaceutically acceptable acid-additive salts, medication based on them, as well as their application. Compounds can be applied for treatment and prevention of diseases mediated by activity of neuropeptide FF receptor, such as pain, hyperalgesia, enuresis, for elimination of syndromes arising in case of alcohol, psychotropic and nicotine addiction, for regulation of insulin release, digestion, memory functions, blood pressure or electrolytic and energy exchange. In general formula II , A together with thiazole ring forms 4,5,6,7-tetrahydrobenzothiazole, 5,6,7,8-tetrahydro-4H-cycloheptathiazole, 5,6-dihydro-4H-cyclopentathiazole fragments; R1 represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tret-butyl, 1,1-dimethylpropyl or phenyl; R2-R6 each represents hydrogen or methyl.
EFFECT: obtaining solutions, which ca be used for treatment and prevention of diseases, mediated by activity of neuropeptide FF receptor.
6 cl, 4 tbl, 106 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to an improved method for synthesis of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole. Method involves the following successive steps: (i) interaction of bromine with 4-acetamidocyclohexanone an aqueous solution to yield 2-bromo-4-acetamidocyclohexanone; (ii) addition of thiourea to yield 6-acetylamino-2-amino-4,5,6,7-tetrahydrobenzothiazole; (iii) addition of hydrobromic acid an aqueous solution to yield 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole without isolation of 6-acetylamino-2-amino-4,5,6,7-tetrahydrobenzothiazole synthesized at stage (ii); (iv) isolation of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole and if necessary separation of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole isolated at stage (iv) for R-(+)- and S-(-)-enantiomers, and isolation of R-(+)- and/or S-(-)-enantiomer. 2,6-Diamino-4,5,6,7-tetrahydrobenzothiazole is used for synthesis of pramipexole. Also, invention relates to a method for synthesis of pramipexole by synthesis of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole by using the method said and its conversion to pramipexole and if necessary by separation of pramipexole for its R-(+)- and S-(-)-enantiomers and isolation of R-(+)- and/or S-(-)-enantiomer.
EFFECT: improved method of synthesis.
15 cl, 1 sch, 3 ex
SUBSTANCE: invention relates to field of organic chemistry, to derivatives of 1,4-diketones, namely to novel biologically active substance -2-(2,4-dichloranilino)-1,4-bis(4-methylphenyl)-2-buten-1,4-dione of formula 1 , which possesses antimicrobial activity and can be applied in medicine.
EFFECT: obtaining novel biologically active substance which possesses antimicrobial activity.
1 cl, 1 ex, 1 tbl
SUBSTANCE: invention describes novel benzothiazinone derivatives of formula (I) and their use as antibacterial agents in infectious diseases caused by bacteria, especially mycobacterium tuberculosis (TB) and leprosy, in which R1 and R2 independently denote NO2, CN, CONR7R8, COOR9 CHO, halogen, SO2NR7R8, OCF3, trifluromethyl; R3 and R4 independently denote H or methyl; R5 and R6 independently denote a straight or branched aliphatic radical having 1-8 members in the chain, or R5 and R6 together denote a divalent radical -(CR9 2)m- or R5 and R6 together denote a divalent radical: R7, R8 and R9 independently denote H or a straight or branched aliphatic radical having 1-7 members in the chain, or phenyl.
EFFECT: design of an efficient method of obtaining benzothiazinone derivatives, a pharmaceutical composition having anti-mycobacterial activity.
12 cl, 6 tbl, 12 ex
SUBSTANCE: method of producing diphtheria toxin or its mutant or fragment involves a fermentation step where the Corynebacterium diphtheriae strain is grown in a fermenter while stirring in order to maintain a homogenous culture and with limited aeration such that partial pressure of oxygen (pO2) in the culture falls to a level which is 4% lower on the bigger part of the fermentation step. Diphtheria toxin or its mutant or fragment is isolated from the culture. The invention also relates to a method of preparing a pharmaceutical composition for treating or preventing diphtheria, which includes a step for fermentative production of the toxin and mixing it with a pharmaceutically acceptable carrier after isolation.
EFFECT: use of the invention leads to high output of diphtheria toxin or mutant (for example, CRM 197), ensures high output of diphtheria toxin when the culture medium additionally contains iron or complex initial substances of varying quality.
20 cl, 6 dwg, 8 tbl, 6 ex
SUBSTANCE: present invention relates to pyrido[1,2-a]benzimidazole derivatives of general formula I, where R=alkyl; R1=alkyl, aryl; R2=alkyl. The invention also relates to a method of producing formula I compounds.
EFFECT: novel to pyrido[1,2-a]benzimidazole derivatives with antibacterial activity are obtained.
2 cl, 2 tbl
SUBSTANCE: invention relates to medicine, namely to treatment of infectious diseases, and can be used in determination of non-specific anti-infectious action of immunomodelling immunobiological preparation (IIP). Essence of method consists in the following: IIP in therapeutically efficient for immunocorrection day dose is perorally introduced to a group of 5-7 monkeys with diarrhea syndrome, in combination with efficient in case of diarrhea syndrome antibiotic, in day dose, which constitutes 1/2 of the dose efficient in case of diarrhea syndrome. After that in case if carried out treatment is inefficient during 2 days, day dose of antibiotic is increased to 3/4 of the dose efficient in case of diarrhea syndrome. Determined is either absence of non-specific anti-infectious IIP action in case when combined application of IIP and antibiotic proves to be inefficient during 7 days, or presence of non-specific anti-infectious IIP action in case when combined application of IIP and antibiotic proves to be efficient.
EFFECT: method allows to determine non-specific anti-infectious IIP action due to determination of minimal efficient in case of diarrhea syndrome day dose of antibiotic in its combination with IIP
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, particularly to pharmaceuticals applied for skin protection against chemical and biological damage factors, bacterial or fungal infections, for prevention of occupational skin diseases, for prevention of contact dermatitis, including allergic dermatitis, and also for first aid and following treatment of wound defects of skin, soft tissues or mucous membranes and can be used in the industry, building, agriculture, medicine and everyday life. Substance of the invention is a therapeutic dermatological composition for local administration which contains an active principle in the form of complex rare-earth salt compounds and a pharmaceutically acceptable carrier.
EFFECT: when applying the pharmaceutical composition based on complex rare-earth salt compounds with polyoxy-compounds in the form of a liquid or soft dosage form, an evident protective and preventive, dermatoprotective and medical effect, no adverse reactions, good tolerance and fast skin repair are observed.
6 cl, 10 tbl, 22 ex
SUBSTANCE: invention refers to medicine, and can be used for integrated treatment of purulent cholangitis by external percutaneous transhepatic drainage and laser and antibiotic therapy. That is ensured by ultrasound-aided percutaneous transhepatic drainage. Then Cefoperazone 2 g in 100 ml of 0.9% saline solution in a plastic package is exposed to low-intensity infra-red pulse laser light at wave length 0.89 mcm, power 200 mWt and frequency 1500 Hz for 6 minutes. Thereafter, the exposed antibiotic substance is introduced intravenously drop-by-drop for 30 minutes. Simultaneously, blood is exposed intravenously to continuous laser light at wave length 0.63 mcm, power 2 mWt for 30 minutes. The therapeutic course of laser and antibiotic therapy is 5-10 days.
EFFECT: method allows preventing purulent-septic complications represented by hepatic abscesses and hepatic failure.
3 cl, 2 ex
SUBSTANCE: invention belongs to vaccine manufacture for infectious diseases prophylaxis. Salmonella vaccine manufacture includes detoxication of exo- and endotoxins in suspention of autoclaved salmonells consecuently with two detoxicants - 0.2% formalin solution at 40±1 C° during 6-7 days and 0.5±0.1% aethonium solution at 41±1 C° during 7-8 days, followed by sterilisation at 1.0 atm during 20 minutes. Derived anatoxins are sorbed on aluminium hydroxide and sterilised at 1 atm during 20 minutes.
EFFECT: anatoxin-vaccine with enhanced effectivity and safety is used for specific prevention of salmonellosis in piglets, calves, carnivorous and poultry.
SUBSTANCE: invention belongs to medicine, notably to pharmaceutical composition for treatment and prevention of bacterial infections induced by gram-positive bacteria. Composition includes effective doses of cholanic acid or its salt, phosphatidylcholine and neutral lipids. Neutral lipids and phospholipids are associated in lipoprotein-like particles, which does not include proteins or peptides.
EFFECT: composition effectivity is caused by its ability to bind lipoteichoic acid of gram-positive bacteria, neutralising or preventing their pathogenic action.
7 cl, 2 tbl, 1 ex
SUBSTANCE: invention relates to pharmaceutical industry, in particular to composition for prevention and treatment of bacterial infections of oral cavity. Composition for prevention and treatment of bacterial infections of oral cavity, containing anthocyanosides, extracted from Vaccinium myrtillus or Vaccinium myrtillus or procyanides extracted from Vitis vinifera, sanguinarines and heleretrines extracted from Sanguinaria canadensis, Macleaya cordata or Macleaya microcarpa and lypophylic extract of Echinacea angustifolia. Application of said components for production of composition for prevention and treatment of bacterial infections of oral cavity. Application of said components for production of composition for oral cavity hygiene. Application of said composition for oral cavity hygiene.
EFFECT: said composition is efficient for prevention and treatment of bacterial infections of oral cavity.
5 cl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to compounds of general formula (I), where R1 - C1-C6alkyl, (C1-C6alkyl)C1-C6alkyl, di(C1-C6)C1-C6alkyl or C3-C6dicloalkyl; each R2 independently represents halogen, C1-C6alkyl, halogen-substituted C1-C6alkyl or cyano; R3 - hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkinyl, hydroxyl, hydroxy-substituted C1-C6alkyl, C1-C6alkoxy, C3-C6cycloalkyl, cyano, C(=O)H, phenyl, (C3-C6cycloalkyl)C1-C6alkoxy, (C1-C6alkoxycarbonylamino)C1-C6alkoxy or (C1-C6alkylcarbonylamino)C1-C6alkoxy; R4 represents hydroxyl, C1-C6alkoxy, the group -NH(C=O)R4a, where R4a is halogen-substituted C1-C6alkyl, or the group -NH(CH2)2OR4b, where R4b is benzyl or phenyl ethyl; and m = 1 or 2 in a free form or in the form of pharmaceutically acceptable salt. Besides the invention refers to a pharmaceutical composition of the compounds applied for treatment or prevention of a disease or condition wherein vaniloid receptor activation acts the part or participates.
EFFECT: invention refers to application of the named compounds for preparing a drug to be applied for treatment or prevention of pain or gastrointestinal disturbance.
20 cl, 30 ex