Meisenheimer complexes having bactericidal and fungicidal activity
SUBSTANCE: invention relates to compounds of general formula (I), where R is n-C12H25 or n-C16H33.
EFFECT: compounds of formula having bactericidal and fungicidal properties.
1 cl, 1 dwg, 1 tbl, 3 ex
The invention relates to the field of organic chemistry, in particular the nitrogen and the oxygen-containing heterocycles, namely complexes (salts) of Meisenheimer General formula I:
where R is n-C12H25(1); n16H33(2),
having high bactericidal and fungicidal activity at low concentrations, which can find application in the field of veterinary medicine and agriculture as drugs and disinfectants.
Known analogue of the claimed compounds on purpose - the active ingredient of many domestic and foreign (France, Germany, the Netherlands) antibacterial, antiseptic drugs - benzalconi chloride (Benzalkonium chloride), which is a chloride alkyldimethyl(phenylmethyl)ammonium [Jansson P.M. Medical encyclopedic dictionary (Collins), Moscow: Astrel, 2006, 1375 S.]. The disadvantage of this drug is its low thermal stability up to 100°C, as well as all of ammonium salts, which when heated decompose the source amines and lose their therapeutic activity. In connection with this difficult and sterilization of these drugs. In addition, all products containing benzalconi chloride, dissolved soap, as stated in the instructions for their use [Burbelo A.T., V. Shabrov Modern medicines. - M.:OLMA Media Group, 2007. - S].
Structural analogs of compounds (I) - complexes of Meisenheimer in aromatic nucleophilic amination, in the world literature is not known to the present work have not been allocated, although are generally recognized intermediates in the reactions of nucleophilic substitution in obtaining products of substitution.
The task of the invention is the creation of new stable complexes of Meisenheimer (I), and has bactericidal and fungicidal activity, extends the known range of the means specified destination.
The technical result is achieved by obtaining stable complexes of Meisenheimer formula (I)have antibacterial and antifungal properties.
The claimed compounds obtained by the interaction of 4,6-dinitrobenzofuroxan (II) at room temperature for 5-7 hours with higher amines (III) in a molar ratio of 1:2 scheme
Source dodecyl - and hexadecylamine (II) and 4.6-dinitrobenzofuroxan are commercially available drugs.
4.6-Dinitrobenzofuroxan, readily available in synthetic terms of the reagent obtained by the method described in the work of German authors [R. Nietski, R. Dietschy. Ber., N.34. - S.55 (1901)]:
Method received what I complexes of Meisenheimer is illustrated by the following examples, but is not limited to them.
Example 1. The method of producing complex Meisenheimer (1)
To a solution of 1.02 g (0,004 mol) 4.6-dinitrobenzofuroxan in 5 ml of abs. ethanol is added a solution of 3.27 g (of 0.017 mol) of n-dodecylamine in 5 ml of abs. of ethanol. The reaction mixture was kept at room temperature (18-20°C) for 72 hours, then cooled and stored in a refrigerator at 0°C. until a crystalline product of orange color in the form of a transparent single crystals druses. The precipitate was separated, washed with ether from the parent compounds, dried. Output 1,91 g (73%), So pl. with decomp. 119,6°C. IR: 3290 cm-1(NH), 1620 cm-1(C=N), 980 cm-1(N-O). Found, %: C 61.12; N, 9.87; N, 15.7830H56N6O6. Calculated, %: C 60.40; N, 9.40; N, 14.10.
Method PCA established the final structure of the salt (1) and is shown in figure 1.
Example 2. The method of producing complex Meisenheimer (2)
To a solution of 1.00 g (0,004 mol) 4.6-dinitrobenzofuroxan in 5 ml of abs. ethanol is added a solution 4,27 g (to 0.016 mol) of n-hexadecylamine in 5 ml of abs. of ethanol. The reaction mixture was kept at room temperature (18-20°C) for 72 hours, then cooled and stored in a refrigerator at 0°C. until a crystalline product of orange color in the form of a transparent single crystals druses. The precipitate was separated, washed with E. the Il from the source connection, dried. The output is 2.41 g (77%), So pl. with decomp. of 127.5°C. IR: 3290 cm-1(NH), 1620 cm-1(C=N), 980 cm-1(N-O). Found, %: C 60.40; H 9.93; N, 12.10 s38H72H6About6. Calculated, %: C 64.41; H 10.17; N, 11.86. Method PCA established the final structure of the salt (2) and shown in figure 2.
Example 3. Study of biological activity
Fungicidal and bactericidal activity of salts of Meisenheimer formulas 1 and 2 were investigated on the test cultures: Candida Albicans, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis [Pershin GN. Methods of experimental chemotherapy. - M.: Medicine, 1971. - 245 C.]. For evaluation of biocidal activity of the investigated substance 1 and 2 as 1% solutions in water were introduced into the wells apparitional nutrient medium. Of bactericidal and fungicidal activity was judged by the presence of zone of inhibition of growth of the test cultures, which is formed around the hole with the test substance. The results of the study fungicidal and bactericidal activity of complexes of Meisenheimer formula I are presented in table 1.
|Fungicidal and bactericidal activity of salts of Meisenheimer 1, 2|
|Staphylococcus aureus||Escherichia coli||Pseudomonas|
|Proteus Mirabilis||Candida Albicans|
Advantages of the proposed compounds is that they have high bactericidal and high fungicidal activity at low concentrations. In addition, they are stable (according to the method of thermogravimetry and scanning calorimetry) to of 224.8°C and not collapse under the action of the soap solution, because they are cationic surfactants, which makes them promising drugs and disinfectants.
Of the investigated prior art is not revealed information about the compounds having such properties, as claimed, that is proof of the compliance of the claimed technical solution Crete is a theory of "novelty", requirements for inventions.
The claimed technical solution is obviously not obvious to a person skilled in the analyzed field of technology, thus, the claimed technical solution meets the criterion of "inventive step"requirements for inventions.
The claimed technical solution meets the criterion of "industrial applicability", presented to the invention, since the inventive complexes of Meisenheimer can be obtained through the use of known components using standard equipment and known methods.
Complexes of Meisenheimer General formula I,
having bactericidal and fungicidal activity.
SUBSTANCE: described are novel benzofuroxanes of general formula
, where R is phenylamino-, N-[4-methoxyphenyl]amino-, N-piperidyl-, which have fungicidal and bactericidal activity and which can be used in veterinary, medicine and agriculture.
EFFECT: high efficiency of the compositions.
2 cl, 2 tbl, 3 ex
SUBSTANCE: invention refers to a new anthelmintic agent representing 5,7-disubstituted-4,6-dinitrobenzofuroxane of general formula , where R1: phenylamine or 3-methylphenylamine.
EFFECT: agent exhibits fast anthelmintic activity.
2 tbl, 4 ex
SUBSTANCE: disclosed compounds can be used as a medicinal agent having CXCR2 inhibiting properties. In formula I , X denotes -CR3=CR4-, -CR5=N-, -N=CR6-, -NR7- or -S-; R3, R4, R5 and R6 independently denote hydrogen, F, CI, Br, I; R7 denotes hydrogen; Y1, Y2, Y3 and Y4 independently denote -CR8- or nitrogen, provided that at least two of Y1, Y2, Y3 and Y4 denote -CR8-; where R8 denotes hydrogen, F, CI, Br, I; A denotes a cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; a bicyclic partially saturated 9-member cycloalkyl; a bicyclic partially saturated 9-10-member heterocycle in which two atoms in the ring are oxygen atoms; phenyl; naphthyl; a 5-6-member heteroaryl in which 1-3 atoms in the ring are oxygen, sulphur and nitrogen atoms; a 9-10-member bicyclic heteroaryl in which 1-3 atoms in the ring are nitrogen, oxygen and sulphur atoms; a 6-member heterocycle in which one atom in the ring is a nitrogen atom and which can be unsubstituted or substituted with alkyl having 1, 2, 3 or 4 carbon atoms, -C(O)CH3, -C(O)CH2CH3, -C(O)cyclopropyl, -C(O)CF3 and -C(O)OC(CH3)3; where phenyl, heterocyclic or heteroaryl radical is substituted with 1, 2 or 3 radicals selected from a group consisting of F, O, Br, I, OH, CN, NO2, SCF3, SF3, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; cycloalkyl having 3, 4, 5 or 6 carbon atoms; alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -NR9R10, C(O)R44, S(O)SR47, -(CH2)k-phenyl, 5-6-member heteroaryl, in which 1-3 atoms in the ring are nitrogen and sulphur atoms; where the phenyl radical may be substituted with F, CI, Br, I; R9 is an alkyl having 1, 2, 3 or 4 carbon atoms; R10 is an alkyl having 1, 2, 3 or 4 carbon atoms; R44 is an alkyl having 1, 2, 3 or 4 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; alkoxy having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms; R47 is an alkyl having 1, 2, 3 or 4 carbon atoms; k equals 0, 1, 2 or 3; s equals 1 or 2; B is -O-C(R11R12), -C≡C-, -CR52=CR53-, -C(R13R14)C(R15R16), -NR17-C(R18R19); R11, R12, R13, R14, R15, R16, R17, R18, R19, R52, R53 independently denote hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; D is C(O)OH, C(O)NHR21 or C(=NR58)NHR22; R21 and R22 independently denote hydrogen, -SO2-alkyl having 1, 2, 3 or 4 carbon atoms, -SO2-phenyl; R58 is OH; R1 and R2 independently denote an alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where the alkyl radicals are unsubstituted or substituted with 1 radical selected from a group consisting of F, Cl, Br, I, phenyl substituted with OH; or R1 and R2, taken together with a carbon atom with which they are bonded form a 3-, 4-, 5- or 6-member carbocycle. The invention also relates to use of formula I compounds in preparing a medicinal agent which has CXCR2 inhibiting properties, to a medicinal agent which containing an effective amount of the disclosed compound and having CXCR2 inhibiting properties, as well as to use of formula II compounds (formula and values of radicals are given in the formula of invention) in preparing a medicinal agent having CXCR2 inhibiting properties.
EFFECT: high effectiveness of application.
10 cl, 384 ex
FIELD: veterinary science.
SUBSTANCE: application of 5,7-disubstituted-4,6-dinitrobenzofuroxane with common formula , where R1: 4-hydrox and phenyl amine or 4,5-dichlorophenylamine as anthelmintic agent.
EFFECT: invention has a quick-acting anthelmintic activity (during 3-45 min).
1 cl, 2 tbl, 4 ex
SUBSTANCE: described are compounds of formula (I), in which Ar represents group of formula (A), (B1), (B2) or (C), or (D1), or (D2); R1, R2, R3, R4, R5, n, A1, A2, A3, A4, A5, Ka, Kb, L, M, V, W, X, Y, Z havevalues, determined in i.1 of invention formula, fungicide composition and method of combatting phytopathogenic fungi or their elimination, using compounds of formula (I).
EFFECT: high fungicide activity.
22 cl, 142 tbl, 34 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel anthranilic acid amides with a by-side heteroarylsulfonyl chain. Invention describes compounds of the formula (I): wherein R1 means compounds of formulae: or wherein A means -CnH2n- wherein n = 0, 1, 2, 3, 4 or 5; D means a bond or -O-; E means -CmH2m- wherein m = 0, 1, 2, 3, 4 or 5; R8 means hydrogen atom, alkyl with 1, 2, 3 or 4 carbon atoms or -CpH2p-R14 wherein p = 1, 2, 3, 4 or 5; R14 means phenyl or heteroaryl wherein phenyl and heteroaryl are unsubstituted or substituted with 1, 2 or 3 substitutes chosen from group consisting fluorine (F), chlorine (Cl), bromine (Br) and iodine (J) atom, alkyl with 1, 2, 3 or 4 carbon atoms; R9 means hydrogen atom or alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms; R10 means hydrogen atom, alkyl with 1, 2, 3 or 4 carbon toms, phenyl, naphthyl or heteroaryl wherein phenyl, naphthyl and heteroaryl are unsubstituted or substituted with 1, 2 or 3 substitutes chosen from group consisting of F, Cl, Br, J, alkyl with 1, 2, 3 or 4 carbon atoms; R11 means cycloalkyl with 3, 4, 5 or 6 carbon atoms, phenyl, furyl, pyridyl, pyrazinyl wherein phenyl, furyl, pyridyl, pyrazinyl are unsubstituted or substituted with 1, 2 or 3 substitutes chosen from group consisting of F, Cl, Br, J, alkyl with 1, 2, 3 or 4 carbon atoms, alkoxy-group with 1, 2, 3 or 4 carbon atoms; R12 means alkyl with 1, 2, 3 or 4 carbon atoms, alkynyl with 1, 2, 3 or 4 carbon atoms, cycloalkyl with 3, 4, 5 or 6 carbon atoms, phenyl or heteroaryl; R13 means -CpH2p-R14 wherein p = 0, 1, 2, 3, 4 or 5; R15 means cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms; R2 means hydrogen atom; R3 means heteroaryl wherein heteroaryl is unsubstituted or substituted with 1, 2 or 3 substitutes chosen from group consisting of F, Cl, Br, J, alkyl with 1, 2, 3 or 4 carbon atoms; R4, R5, R6 and R7 mean independently of one another hydrogen atom, F, Cl, Br, J, alkyl with 1, 2, 3 or 4 carbon atoms, alkoxy-group with 1, 2, 3 or 4 carbon atoms, and their pharmaceutically acceptable salts also. Also, invention describes pharmaceutical composition containing compounds of the formula (I) possessing the effect blocking Kv1.5-channel. Proposed compounds can be used in treatment and prophylaxis of diseases mediated by K+-channel.
EFFECT: valuable medicinal property of compounds and pharmaceutical composition.
20 cl, 4 tbl, 70 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a method for synthesis of benzofurazans by reduction of benzofuroxanes in ethylene glycol medium. Sulfur is used as a reducing agent and taken in the amount 0.5-1.0 g-atom per 1 g-mole of furoxane, and the process is carried out at temperature 140-155°C. Proposed method for reduction of benzofuroxanes with sulfur in ethylene glycol is safety and economy.
EFFECT: improved method of synthesis.
FIELD: organic chemistry.
SUBSTANCE: invention relates to 5,7-disubstituted 4,6-dinitrobenzofuroxanes of the general formula (I): wherein R1 represents: 2-chlorophenylamino-group of the formula , 2,5-dichlorophenylamino-group of the formula , 4,5-dichlorophenylamino-group of the formula , 2-hydroxyphenylamino-group of the formula , 4-hydroxyphenylamino-group of the formula , 4-bromophenylamino-group of the formula , 2-methyl-5-chlorophenylamino-group of the formula and 4-aminodiphenyl of the formula that elicit acaricidal and bactericidal activity in low concentrations. These compounds can be used in veterinary science, medicine and agriculture.
EFFECT: valuable properties of compounds.
2 tbl, 5 ex
< / BR>or their salts, where in the formula Ia W represents N or C-CO-R, where R denotes HE OC1-C6alkyl or NR3R4where R3and R4- N or C1-C6alkyl, or formula Ib Az denotes imidazopyridine and in both formulas Ia and Ib R1represents C1-C4alkyl, R2denotes phenyl fragment or 2,5-cyclohexadiene-3,4-ridin-1 silt fragment
SUBSTANCE: group of inventions refers to dental compositions for treating or preventing dry mouth syndrome. One of the versions of the composition for treating and/or preventing dry mouth syndrome and at least one accompanying pathology represents a composition containing at least one surfactant, at least one antimicrobial agent and at least one adhesive where at least one antimicrobial agent is sterically immobilised in a complex with one or more glycosaminoglycans. Said composition can represent a tooth paste, a tooth elixir or an oral spray. The other version of the composition contains at least one surfactant, at least one antimicrobial agent, and at least one adhesive; wherein at least one antimicrobial agent represents cetylpyridinium chloride in a complex with one or more glycosaminoglycans.
EFFECT: compositions provide the effective delivery of antimicrobial agents to oral mucosa, exhibits low irritability and high moisture-binding capacity.
18 cl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to a new medication possessing antiviral, antibacterial and fungicide activity and representing 2-(2,5-dimethyl)pyrazolyl-3-hydroxy-4(3H)-chinazolinon with formula I Additionally, the invention relates to a method: for production of compounds with formula I. The method consists in subjecting 3-hydroxy-4(3H)-chinazolinon to interaction with hydrazine resulting in formation of 2-hydrazino-3-hydroxy-4(3H)-chinazolinon that is then subjected to interaction with acetyl acetone to produce the target product.
EFFECT: production of new medication possessing antiviral, antibacterial and fungicide activity.
2 cl, 3 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, more specifically a pharmaceutical gel exhibiting antimicrobial and antifungal action. The presented gel contains as active ingredients betamethasone dipropionate (0.01-0.3 wt %), gentamycin sulphate (0.02-0.6 wt %) and terbinafine hydrochloride (0.8-5.0 wt %), and as excipients - propylene glycol (10.0-40.0 wt %), UV filter Escalol 567 (1.0-40.0 wt %), cyclomethicone DC 345 (5.0-20.0 wt %), organosilicone emulsifier DC 5329 - (1.0-4.0 wt %), organosilicone elastomer DC 9045 (5.0-50.0 wt %), antioxidant Tinogard NOA (0.02-0.1 wt %), acrylate emulsion of copolymer Salcare SC80 (1.0-3.5 wt %), trometamol (1.0-2.5 wt %), preservative Sharomix MCI (0.1-0.5 wt %), purified water (to 100.0 wt %).
EFFECT: due to said composition of excipients the invention provides skin protection against ultra-violet radiation and improved penetration of active ingredients in derma.
3 ex, 1 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is offered is applying 10-[(3R)-1-azabicyclo[2.2.2]oct-3-ylmethyl]-10H-phenothiazine (V0162), as well as its pharmaceutically acceptable salts for preparing a drug applicable for treating or preventing urinary incontinence and related disorders caused by bacterial or mycotic infections developed due to cystic hyperactivity by means of selective inhibition of M1, M2- and M3-muscarine receptors in local and/or oral application.
EFFECT: V0162 decreases intracystic pressure, promotes anticholinergic action in vivo, effectively passes through a mucous membrane, reaching the levels involved in its anticholinergic activity, and when delivered locally has no toxic action neither histologically relation, nor with respect to the vital functions: respiratory rate, pulse, behaviour.
8 cl, 5 tbl, 5 ex
SUBSTANCE: invention relates to a novel broad-action fungicidal agent which is a salt of 2,4-dioxo-5-(2-hydroxy-3,5-dichlorobenzylidene)amino-1,3-pyrimidine of general formula: or dimer thereof: , where X is selected from: Na+, K+, Li+, NH4 +.
EFFECT: agent can be used to treat fungal diseases, as well as prevent damage to different materials and agricultural products by fungi.
SUBSTANCE: present invention relates to versions of a method of purifying terbinafine from nonmetallic impurities, primarily a substance A of formula
, as well as to use of said methods to obtain purified terbinafine. One of the versions of the method involves molecular distillation of crude terbinafine in form of a free base and extraction the obtained purified terbinafine in form of a free base or acid-addition salt (method A). In another version (method B), crude terbinafine in form a free base undergoes molecular distillation combined with formation of a salt of the obtained product with simultaneous deposition of a purified trans-isomer, and the obtained highly pure terbinafine is extracted in form of a free base or acid addition salt.
EFFECT: method enables to obtain terbinafine containing less than approximately 5 ppm of substance A.
13 cl, 2 dwg, 6 ex
SUBSTANCE: present invention refers to N-phenyllepidine salts tritium labeled in the phenyl substitution group with the general formula: Moreover, the invention refers to the way of production of tritium labeled N-phenyllepidine salts.
EFFECT: new compounds that are characterized by antibacterial and antifungal action, and development of the way of their production.
2 cl, 1 dwg, 1 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine and pharmaceutical industry. A pharmaceutical composition for outward application for treating allergic and inflammatory skin diseases contains a glucocorticosteroid specified in a group: mometasone or its derivatives, betametasone or its derivatives, beclometasone or its derivatives, dexametasone or its derivatives, flumetasone or its derivatives; as an antibacterial quinolone compound, it contains a compound specified in a group: ofloxacin, lomefloxacin, norfloxacin, pefloxacin, ciprofloxacin, levofloxacin, sparfloxacin, moxifloxacin; as an antifungal azol compound, it contains a compound specified in a group: clotrimazole, ketoconazole, myconazole, fluconazole, itraconazole, voriconazole and additionally contains a synthetic polymeric high-molecular compound, particularly polyvinyl pyrrolidone, or polymers or copolymers of acrylic and metacrylic acid, or polyvinyl alcohol, or siloxane or silane polymers in certain proportions.
EFFECT: invention provides higher effectiveness in inflammatory and allergic skin diseases with no side reactions and systemic exposure.
2 tbl, 80 ex, 3 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine and cosmetology, and represents a bactericidal nail care polish containing a water-soluble film-forming hydroxyalkyl chitosan or carboxyalkyl chitosan material, a bactericidal agent, a polar aqueous-alcoholic solvent which as the bactericidal agent contain bentonite powders nanostructured to particle size 150 nm and less, and intercalated by metal ions Ag+ or Ag+ and Zn2+, or Cu2+ and Zn2+, or Ag+ and Cu2+ and Zn2+ which are introduced into a prepared emulsion of the film-forming material in the form of 4-10 % hydrosol; the components of the composition are taken in certain proportions, wt %, and the weight ratio parts of the mixtures of bentonite powders intercalated by metal ions is: for metal ions Ag+ and Zn2+ (1:(0.5÷1)); for metal ions Cu2+ and Zn2+ (1÷0.5):(0.5÷1); for metal ions Ag+ and Cu2+ and Zn2+ 1:(0.5):(0÷1).
EFFECT: invention provides extended range of polishes, reduced risks of negative dermatological manifestations, effective bactericidal protection.
6 cl, 8 ex, 2 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is offered is a sulphur terpene compound, namely terpene sulphide of formula (2-(1'-hydroxy-4'-isopropenyl-1'-methylcyclohexyl-2'-thio)-methyl ethanoate) exhibiting fungicidal and anti-inflammatory action. It is applicable as an antiseptic additive in building and paint-and-lacquer materials for modern building and finishing. Terpene sulphide in equitoxic doses exhibits anti-inflammatory action, and also can be used in medical practice as an agent exhibiting fungicidal action and used for treating mycotic skin diseases accompanied by manifested inflammatory process.
EFFECT: wide spectrum of fungicidal action of (2-(1'-hydroxy-4'-isopropenyl-1'-methylcyclohexyl-2'-thio)-methyl ethanoate) in a combination with low toxicity and low production cost is shown.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics. A composition contains nanosized silver powder, nanosized aluminium powder and nanosized diamond powder in the following proportions, wt %: nanosized silver powder - 40, aluminium powder -30, nanosized diamond powder -30.
EFFECT: composition shows a combined immunomodulatory and antibacterial effect, low toxicity.
3 tbl, 1 ex