2,2,5,5-tetrabromo-1,6-di-(41-methylphenyl)-1,3,4,6-hexanetetraone possessing antibacterial activity
FIELD: organic chemistry, chemical technology, microbiology.
SUBSTANCE: invention relates to novel 2,2,5,5-tetrabromo-1,6-di-(4'-methylphenyl)-1,3,4,6-hexanetetraone of the formula (I): that possesses antibacterial activity. Compound of the formula (I) is synthesized by interaction of 3,4-dihydroxy-1.6-di-(4'-methylphenyl)-2,4-hexadiene-1,6-dione with bromine in chloroform medium. Compound of the formula (I) possesses antibacterial activity with respect to Staphylococcus aureus with MAC (maximum allowable concentration) value = 0.0075-0.06 mcg/ml and to colon bacillus with MAC value = 0.12-0.32 mcg/ml and with the acute toxicity value LD50 = 2960 mg/ml.
EFFECT: valuable activity of compound.
1 tbl, 1 ex
The invention relates to the field of organic chemistry, derivatives polycarboxylic compounds, namely to new biologically active substances of 184.108.40.206-tetrabrom-1,6-di-(41-were)-1,3,4,6-hexanetriol formula (I):
which can find application in medicine as an antimicrobial drug.
The closest structural analogue of the claimed compound is 1,6-di-(41-were)-2,2,5,5-tetrachloro-1,3,4,6-hexane-tetraen (II) [Kasatkina US, V.V. Lapin, Hidow NM, Kozminykh V.O., Novikov V.V., Odegova TF Synthesis and bacteriostatic activity of 1,6-disubstituted of 220.127.116.11-tetrachloro-1,3,4,6-hexane-Ronov. // Proc. Dokl. Actual problems of formats. science and education: results and prospects. Perm, 2001 - P.44-45]
possessing antimicrobial activity.
As a benchmark comparison, we have used antimicrobials - dioxidine [Mashkovsky PPM Medicines. M: New wave, 2000, Vol.2, s-299] and fluconazole [ibid, s-362], widely used in medical practice.
The purpose of this invention is the synthesis is not described previously of 18.104.22.168-tetrabrom-1,6-di-(41-were)-1,3,4,6-hexanetriol having antimicrobial action.
This goal is achieved by the receipt of 22.214.171.124-tetrabrom-1,6-di-(41-m is terphenyl)-1,3,4,6-hexanetriol reaction of 3,4-dihydroxy-1,6-di-(4 1-were)-2,4-hexadien-1,6-dione (III) [Hidow NM, Kozminykh E.N., Sofina O.A., Shironina T.M., Kozminykh V.O. Synthesis of 1,6-diaryl-3,4-dihydroxy-2,4-hexadiyn-1,6-diones and their derivatives of 2,3-furandione. // Chemistry of heterocycle. connect. - 1999. No. 11. - S-1475] with bromine in the environment of chloroform:
Example obtain the claimed compound (I)
To a mixture of 0.64 g (0.002 mol) of 3,4-dihydroxy-1,6-di-(41-were)of 2,4-hexadiyn-1,6-dione and 1 g of sodium carbonate in 80 ml of chloroform was added dropwise 1.28 g (0,008 mol) of bromine in 20 ml of chloroform. Stirred on a magnetic stirrer for 2 h prior to the bleaching solution. The solution is filtered and evaporated. The dry residue is recrystallized from toluene. Get 0,82 g (64%) of crystalline compound (I) with Tpl.203-204 (decomp). C18H8Br6About4. IR spectrum, νcm-1(the crystals): 1760 (CO), 1710 (CO). Range of TMR, δ, M. D. CBCl3: 2.44 (6N, 2CH3), 7.23 D., 7.92 D. (8H, 2C6H4).
The obtained compound (I) is a yellow crystalline substance, soluble in dimethyl sulfoxide and dimethylformamide, sparingly soluble in chloroform, toluene, insoluble in hexane and water.
The claimed compound was tested for the presence he has antimicrobial activity.
Determination of the bacteriostatic the th activity was performed by the method of twofold serial dilutions in liquid nutrient medium [Manual on experimental (preclinical) study of new pharmacological substances. - M., 2000, s-273]. For all the studied compounds were determined IPC in respect of pharmacopoeial strains: S. aureus ATCC 6538-P, E. coli ATCC 25922, C. albicans ATCC 885-653, P. aerugenosa ATCC 9027. 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 suspension 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 250 000 M.L./ml of the Studied compound in the amount of 0.05 g was dissolved in 5 ml of DMSO, 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 h of exposure control and experimental tubes in the incubator at 37 ° °C. Minimum noise reduct the expansion of the 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 dioksidina [Padalka E.N., INF. and antimicrob, terap., 2001, No. 5, s-155]. Antifungal activity was compared with the action of fluconazole [Rex J.Y., Wals T.J., Sobel J.D. et all, Clin. Infect/ Dis., 2000, V.30, No.4, R-668].
Acute toxicity (LD50) the claimed compounds was studied on white laboratory mice of both sexes weighing 19-20, Investigational compound was administered once in the stomach in the form of starch mucus in volume 1480, 2960, 4440, 5920, 7400 mg/kg, respectively, the observation of the animals was performed within 10 days. Statistical processing of results was carried out according to Prozorovsky CENTURIES comparison of median lethal dose (LD50) at P=0.05 [Prozorovsky CENTURIES, Prozorovsky BTW, Demchenko V.M. Pharmacol. and toxicol., 1978, No. 4, s-502]. The results are shown in the table.
As can be seen from the table, the compound (I) exceeds antimicrobial activity dioxidine to S.aureus not less than 8330 times, E.coli is not less than 32.5 times, P.aerugenosa the same. The compound (I) antifungal activity of C. albicans is comparable with the activity of fluconazole. The compound (I) according to the classification Izmerov NF[Izmerov NF Parameters toxicometric industrial poisons in a single, M, Medicine, 1977, s] belongs to the class of practically non-toxic drugs.
Thus, of 126.96.36.199-those who rubrum-1,6-di-(4 1-were-1,3,4,6-hexane-tetraen) (I) exerts pronounced antibacterial activity and is practically non-toxic. Therefore, the claimed compound (I) can be used in medicine as an antimicrobial drug.
Antimicrobial activity and acute toxicity of compounds I.
|Connection||S.aureus,ug/ml||E. coli mg/ml||P.aeruginosa, ug/ml||C.albicans, ug/ml||LD50mg/kg|
of 188.8.131.52-tetrabrom-1,6-di-(41-were)-1,3,4,6-hexanetriol formula
possessing antimicrobial activity.
FIELD: organic chemistry.
SUBSTANCE: invention relates to method for production of fluorinated ketone of general formula 5 . Claimed method includes reaction of compound of formula 3 , containing at least 30 wt.% of fluorine with fluorine in liquid phase, containing solvent selected from group comprising perfluoroalkane, perfluorinated ester, perfluorinated polyether, chlorofuorohydrocarbon, chlorofluoropolyether, perfluoroalkylamine, inert liquid, compound of formula 2 , compound of formula 6 to produce compound of formula 4 , followed by dissociation of ester bond in formula 4 in presence of KF, NaF or activated carbon without solvent. In formulae: RA represents, optionally containing ether-forming oxygen atom, wherein each of said groups contains C1-C10 carbon atoms; RAF represents C1-C10-perfluorenated RA group; RB represents alkyl optionally containing ether-forming oxygen atom, partially halogenated alkyl, optionally containing ether-forming oxygen atom, wherein each of said groups contains C1-C10 carbon atoms; RBF represents C1-C10-perfluorenated RB group; RC and RCF groups are identical ones and each RC and RCF contains C2-C10 carbon atoms and represents perfluorenated alkyl optionally containing ether-forming oxygen atom, partially halogenated alkyl, optionally containing ether-forming oxygen atom or RA and RB together form alkylene group optionally containing ether-forming oxygen atom, partially halogenated alkylene, optionally containing ether-forming oxygen atom, wherein each abovementioned group contains C3-C6 carbon atoms; each RAF and RBF are perflurenated RA and RB groups containing C3-C6 carbon atoms; groups are identical ones and each RC and RCF contains C2-C10 carbon atoms and represents perfluorenated alkyl optionally containing ether-forming oxygen atom, partially halogenated alkyl, optionally containing ether-forming oxygen atom. Method of present invention provides fluorinated ketone production with 71-96 % yield. Some intermediates of formula 3 also are described.
EFFECT: method for fluorinated ketone production with increased yield.
10 cl, 5 ex
FIELD: industrial organic synthesis.
SUBSTANCE: invention relates to a method for preparation of multivalent carbonyl compounds and to a novel polyvalent carbonyl compound, which may be useful, for example, as intermediate in production of various fluorinated compounds. Polyvalent carbonyl compound is prepared through economically advantageous way from inexpensive substances and with no need of using any complex synthesis stage. In particular, polyvalent alcohol, including alcohols with at least two structures selected from primary, secondary, and tertiary structures, is brought into reaction with acid halide to form polyvalent ester, which is then fluorinated in liquid phase to form perfluorinated polyvalent ester, in which ester bonds, provided by reaction with primary and secondary alcohols, are further cleaved.
EFFECT: expanded synthetic possibilities in organofluoric compound area.
8 cl, 3 dwg, 2 ex
FIELD: organic chemistry, pharmacology.
SUBSTANCE: invention relates to intermediate diketone of formula , wherein R1 is selected from -CHF2, -CF3, -CClF2CF3, -CF2CF2CF3; R1 is hydrogen or halogen; RQ is hydrogen, methyl or methoxy, provided that at least one from R1 and RP is not halogen when RQ is hydrogen.
EFFECT: intermediate for 3-halogene-1H-pyrasole synthesis having pharmacological activity, including hypoglycemic and anti-inflammatory activity.
7 cl, 2 ex
FIELD: medicine, chemical-pharmaceutical industry.
SUBSTANCE: invention relates to an antiviral agent as gel. Agent comprises human leukocyte interferon and 2-% solution of styrene copolymer and maleic anhydride as gel-forming base in the following ratio of the agent components, in 1 g of the agent: concentrated interferon, 5000-10000 IU; nipagin, 0.002-0.004 g and a base, the balance. Proposed agent possesses high activity, nontoxic and possesses antiviral, immunomodulating, anti-inflammatory and regenerative effects and can be used in ophthalmology, dermatology, gynecology and surgery for topical using and in treatment of viral diseases.
EFFECT: valuable medicinal properties of agent.
2 tbl, 2 ex
FIELD: medicine, pediatrics, obstetrics.
SUBSTANCE: method involves administration of preparations balans-narine-f and calcemin. Carrying out this therapy provides decreasing the content of staphylococci in breast milk, increasing the sterility period of milk based on reducing cellular membranes penetrability and to diminish probability in development complications in treatment of bacteriolactia in nursing women. Invention can be used in treatment of staphylococcus bacteriolactia in women.
EFFECT: improved method of treatment.
1 tbl, 2 ex
FIELD: medicine, pharmacology.
SUBSTANCE: invention relates to a medicinal agent used in treatment of warts. Proposed agent contains an active compound chosen from isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, ethyl myristate, propyl myristate, butyl myristate and/or ethyl oleate and at least a mixture containing (-)-epicatechol, (-)-epicatechol gallate, (-)-epigallocatechol, (-)-epigallocatechol gallate, (+)-gallocatechol and (-)-gallocatechol gallate possessing the enhanced effectiveness.
EFFECT: valuable medicinal properties of drug.
7 cl, 2 ex
FIELD: veterinary science.
SUBSTANCE: invention proposes a preparation containing myramistin, chitosan and distilled water taken in the following ratio of components, wt.-%: myramistin : chitosan : water = (0.015-0.1):0.2:100, respectively. The preparation shows high effectiveness, strongly expressed wound-healing effect and bactericidal activity and simplicity in using. Invention can be used in treatment of animals with wounds of different etiology and anatomical localization, weeping eczema, burns and others.
EFFECT: valuable medicinal properties of preparation.
1 tbl, 3 ex
FIELD: synthesis of biologically active compounds.
SUBSTANCE: invention provides novel urea-substituted imidazoquinoline ethers depicted by general formula I: (1), in which X represents -CHR5- or -CHR5-alkyl group; R1 is selected from radicals: -R4-NR8-CR3-NR5-Z-R6-Alk, -R4-NR8-CR3-NR5-Z-R6-Ph, -R4-NR8-CR3-NR5-Z-R6-furanyl, -R4-NR8-CR3-NR5R-7, phenyl being optionally substituted by one or more substituents selected from methyl, methoxy, methylthio, cyano, hydrogen, dimethylamino, and acetyl; R2 is selected from hydrogen, alkyl, and alkyl-Y-alkyl; R3 represents =O or =S; R4 represents alkyl optionally substituted by one or several O-groups; each of R5 represents C1-C10-alkyl; R6 represents ordinary bond or alkyl; R7 forms cycle together with R5; R4 represents hydrogen, C1-C10-alkyl, or forms morpholine ring together with R8; Y represents -O-; Z ordinary bond, -CO-, or -SO2-; n=0; each of R is independently selected from C1-C10-alkyl, C1-C10-alkoxy, hydroxy, halogen, and trifluoromethyl; or pharmaceutically acceptable salt of forgoing compounds. Described are further compounds of general formula II, intermediates of compounds of general formulae III and IV, pharmaceutical compositions based on compounds I and II, which are immunomodulators for synthesis of cytokines based on compounds I and II, methods of treating viral diseases utilizing compounds I and II, and methods of treating tumor diseases utilizing compounds I and II.
EFFECT: expanded synthetic possibilities in quinoline series and increased choice of therapeutically useful compounds.
25 cl, 4 tbl, 44 ex
FIELD: pharmaceutical chemistry.
SUBSTANCE: invention relates to phenylpyridazine derivative of general formula I , wherein R1 represents C1-C12-alkyl optionally comprising cyclic C3-C6-alkyl structures and optionally substituted by phenyl, which may be substituted by 1-2 halogen atoms; or C1-C12-alkenyl substituted by optionally halogen-substituted phenyl; R2 and R3, independently form each other, represent hydrogen, C1-C12-alkyl, C1-C12-hydroxyalkyl, C1-C12-dihydroxyalkyl, or C1-C12-alkynyl; or R2 and R3, together with adjacent nitrogen atom form 5-6-membered saturated heterocyclic group containing 1-2 nitrogen atoms and optionally oxygen atom, indicated heterocyclic group being optionally substituted by C1-C12-alkyl group, C1-C12-alkoxydicarboxylic group or phenyl-C1-C7-alkyl group; X, Y, and Z, independently form each other, represent hydrogen, halogen, optionally halogen(s)-substituted C1-C12-alkyl, C1-C12-alkoxy, C1-C12-alkylthio, C1-C12-alkylsulfinyl, C1-C12-alkylsulfonyl, or phenyl; and n is a number from 0 to 5; provided that R2 and R3 cannot be simultaneously hydrogen atoms or identical C1-C3-alkyl groups when R1 is benzyl or C1-C3-alkyl group; and salts of compounds I. Foregoing compounds manifest inhibitory activity against production of interleukin IL-1β being well dissoluble in water and characterized by good oral absorption. Invention also relates to therapeutical agent inhibiting production of interleukin 1β, pharmaceutical composition, employment of above-defined compounds, a method for treating disease caused by interleukin 1β production stimulation as well as methods for treating immune system disturbances, inflammatory conditions, ischemia, osteoporosis, or septicemia using above compounds.
EFFECT: expanded therapeutical possibilities.
22 cl, 4 dwg, 2 tbl, 217 ex
FIELD: medicine, gynecology, urology.
SUBSTANCE: on isolating Chlamydia out of infection foci and setting a preliminary diagnosis it is necessary to determine their sensitivity to different etiotropic preparations. Then it is important to sample a patient's blood followed by centrifuging and dividing it into plasma, erythrocytic mass and leukocytic suspension. Removed blood plasma should be substituted with physiological solution, and autoerythrocytes should be returned for a patient in physiological solution intravenously by drops. Autoleukocytic suspension should be activated with laser radiation of He-Ne laser at λ=0.63 mcm. Then it should be supplemented with etiotropic preparation moxyfloxacin to be intravenously injected for a patient. The procedure should be repeated daily for about 10-12 d. The innovation suggested enables to shorten the terms of interrupting the main clinical manifestations of the disease due to a purposeful transport of etiotropic preparation being of higher bacteriological efficiency in leukocytes activated with laser radiation, into primary (urogenital tract) and secondary (extraurogenital) foci of inflammation and, also, decrease side action of chemopreparations due to decreasing their course dosage.
EFFECT: higher efficiency of therapy.
FIELD: medicine, immunology.
SUBSTANCE: the present innovation deals with specific prophylaxis of smallpox and viral hepatitis B. The kit contains two tablets each contains stabilizing additives, a filler and lyophilized alive viral material worked out based upon recombinant VOV strain at typical VOV properties expressing proteins preS2-S and HBs virus of hepatitis B virus, the first immunizing dosage corresponds to minimal quantity of viral material being sufficient to obtain weak immune response in the body in case of insignificant at insignificant reactogenicity, and immunizing dosage of the second - maximal quantity of viral material that causes pronounced and prolong immune response in the body at no negative side action. The technique of applying the kit of bivaccine tablets, first, one should use the 1st tablet at minimal dosage of bivaccine, as for the 2nd tablet - with maximal dosage of bivaccine it should be taken till the moment of developing humoral answer (in 7-14 d) after injecting the 1st tablet at minimal immunizing dosage of bivaccine. The innovation enables to create stable immunity.
EFFECT: higher efficiency.
4 cl, 5 ex, 6 tbl
FIELD: veterinary science, virology, biotechnology.
SUBSTANCE: the suggested vaccine contains the suspension of avirulent and purified antigenic material out of the strain N 101 of cattle rotavirus (Research Institute of Animal Protection) obtained in mono-layer culture cells MDBK or SPEV at accumulation degree being 106 viral particles/ml, not less and activity in IEA being 5.0 log2, not less, and target additives: aluminum hydroxide and saponin in efficient ratios. The strain is deposited in collection of FGU VGNKI under registration number - a culture strain N 101 Research Institute of Animal Protection-DEP. The suggested vaccine is highly immunogenic, safe and areactogenic, it is capable to protect cattle stock against epizootic agent of rotaviral infection circulating in Russian territory.
EFFECT: higher efficiency.
14 cl, 9 ex, 10 tbl
FIELD: chemical-pharmaceutical industry.
SUBSTANCE: the suggested preparation contains sweet flag, perforated St.John's wort, common calendula, common yarrow, purple ecchinacea. Decoction should be prepared upon water passed through silver electrodes. The innovation provides decreased side reactions from anti-tuberculosis preparations of toxico-allergic character applied during prolonged period of time.
EFFECT: higher efficiency.