2-(2,4-dichloranilino)-1,4-bis(4-methylphenyl)-2-buten-1,4-dion, possessing antimicrobial activity
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
The invention relates to the field of organic chemistry, derivatives of 1,4-diketones, namely a previously unknown new biologically active compound is 2-(2,4-dichloraniline)-1,4-bis(4-were)-2-butene-1,4-dione of formula 1:
which can find application in medicine as an antimicrobial drug.
The closest structural analogues of the claimed compounds are aminopenicillanic 2, which have claimed compounds 1 same aminopenicillanic fragment [Ehitatava, Lddevelop, Relbopaserca, Lioresal. Journal of organic chemistry, 1969, vol 5, VIP, s-2119].
Structural analogs of compounds 1 can also be considered as substituted 2-amino-4-aryl-4-oxo-2-butenova acids and their esters 3, exhibiting antimicrobial and analgesic activity [Antonimina, Ahomelae5v, Woosley, Rod, Tradeshow. Chemical and pharmaceutical journal, 2002, T.36, No. 11, p.28-30. Nevkritova, Woosley, Avialbility, Antonimina, Waikola, Sagulenko. Chemical and pharmaceutical journal, 1998, 32, No. 9, p.32-35].
All these analogues 2, 3 contain common with the claimed compounds 1 aminophenylamino fragment. The differences consist in the fact that as the substituents R and R' claimed in the x compounds is n-colligny Deputy, R"=H, as R"' - 2,4-dichloroaniline Deputy.
As a benchmark comparison, we have used antimicrobials - cefepime [Yakovlev S.V., eng. the honey. journal, 1998, Vol.6, No. 22, s-1457] and chlorhexidine digluconate [Padalka E.N., INF. and antimicrob. terap., 2001, No. 5, s-155], widely used in medical practice antibiotic and disinfectant.
The purpose of this invention is the synthesis of previously undescribed 2-(2,4-dichloraniline)-1,4-bis(4-were)-2-butene-1,4-dione, having antimicrobial action.
This goal is achieved by obtaining 2-(2,4-dichloraniline)-1,4-bis(4-were)-2-butene-1,4-dione and a study of its antimicrobial action.
Example obtain the claimed compound 1:
A mixture of equimolar amounts of getaway.location and 2,4-dichloraniline boiled in benzene for 5 minutes the Solvent was evaporated. The precipitate was recrystallized from carbon tetrachloride. A yield of 75%. TPL 147-148°C. IR spectrum, cm-1: 1668 (C(1)=0), 1605 (C(4)=0, C=C). An NMR spectrum1N, ppm: 2.36 (s, 6N, me); 6.13 (s, 1H, CH); 6.97 (m, 7H, Ar); 7.76 (d, 4H, N(2), N(6),3J=8.4); 12.35 (s, 1H, NH). Found, %: C 66.72; H 3.80; Cl at 17.85; N, 3.50. C22H15Cl2NO2. Calculated, %: C 66.68; H 3.82; Cl 17.89; N, 3.53.
The obtained compound 1 is a yellow crystalline substance, soluble in alcohols, chloroform, toluene, dimethyl sulfoxide and dimethyl mamide, insoluble in alkanes and water.
The claimed compound was tested for the presence he has antimicrobial activity.
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), 2000., s-273]. For all the studied compounds were determined IPC in respect of pharmacopoeial strains: S. aureus was ATSS 6538-P, E. coli was ATSS 25922, C. albicans was ATSS 885-653, P. aerugenosa ADS 9027, B. cereus was ATSS 8035, B. subtilis was ATSS 6633, S. epidermidis was ATSS 14990. 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 MT/ml were prepared working solution of bacteria with a concentration of 5 million MT/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 stood the sludge 250000 m so/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 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 effect of cefepime [Yakovlev ST., Eng. the honey. journal, 1998, Vol.6, No. 22, s-1457], chlorhexidine digluconate [Padalka E.N., INF. and antimicrob, terap., 2001, No. 5, s-155].
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 table 1.
As can be seen from table 1, compound 1 on antimicrobial activity comparable with the activity of chlorhexidine digluconate against S.aureus and E.coli. Connection 1 with respect to .albicans, spore-forming rods, S.epidermidis inferior to Comparators. In relation to P.aerugenosa activity is not. Connection 1 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, 2-(2,4-dichloraniline)-1,4-bis(4-were)-2-butene-1,4-dione 1 shows a pronounced antimicrobial activity and is practically non-toxic. Therefore, the claimed compound 1 can be used in medicine as an antimicrobial drug.
|Antimicrobial activity (μg/ml) and acute toxicity of compounds 1|
Sources of information
1. Izmerov NF Parameters toxicometric industrial poisons in a single, M, Medicine, 1977, s.
2. Kozminykh E.N., Belyaev S.A., Kozminykh V.O., Makhmudov P.P., Odegova TF Chemical and pharmaceutical journal, 2002, T.36, No. 11, p.28-30.
3. Kolotov, NV, Kozminykh V.O., Devilkin EV, Kozminykh E.N., Call WE, Shelenkov S.A. Chemical and pharmaceutical journal, 1998, 32, No. 9, p.32-35.
4. Padalka E.N., And the F. and antimicrob, terap., 2001, No. 5, s-155.
5. Prozorovskiy CENTURIES, Prozorovsky M. P., Demchenko V.M. Pharmacol. and toxicol., 1978, No. 4, s-502.
6. Manual on experimental (preclinical) study of new pharmacological substances - M., 2000, s-273.
7. Titova H., Gavrilova L.D., Bladework R.L., Vereshchagin LI the Journal of organic chemistry, 1969, vol 5, VIP, s-2119.
8. Yakovlev S.V. Russian journal of medicine in 1998. - V.6, №22. - s-1457.
2-(2,4-dichloraniline)-1,4-bis(4-were)-2-butene-1,4-dione of formula 1:
possessing antimicrobial activity.
SUBSTANCE: invention relates to novel nonsteroid synthetic derivatives with the following structures or their pharmaceutically acceptable salts:
, , ,
, which are capable of modulating the androgen receptor.
EFFECT: invention relates to pharmaceutical compositions containing said derivatives and use thereof to make nonsteroid medicinal agents for treating and/or preventing conditions or diseases such as prostate hyperplasia, prostate cancer, hirsutism, severe hormone-dependant alopecia or acne etc, resulting from antagonistic activity towards the androgen receptor.
6 cl, 5 dwg, 3 tbl,12 ex
SUBSTANCE: invention concerns new photoinitiators, method of their obtainment, compositions hardening with irradiation, and application of those compositions in coating preparation. Invention claims photoinitiators of formulae I , where R1, R2, R3 and R4 are independently C1-C8alkyl or benzyl; or R1 and R2 together and/or R3 andR4 together are cyclohexyl; R5 is hydrogen; A is OH, Br, -O-C1-C12alkyl, -O-R7, where R7 is linear or forked C2-C21hydroxyalkyl carbon chain interrupted by 1 to 9 oxygen atoms; or -NR8R9, where R8 and R9 are independently C1-C21alkyl or C2-C4alkyl substituted by one or more OH groups; A' is -O-; X and Y are independently -OH or -N(CH3)2; n is 2; R6 is linear or forked divalent -CO-NH-(C2-C16alkylene)-(NH-CO)- radical or linear or forked -CO-NH-(C0-C9alkylene)-(NH-CO)- which can be interrupted by phenylene, or linear or forked divalent -C2-C50alkylene radical with carbon chain interrupted by 1 to 15 oxygen atoms.
EFFECT: efficient method of obtaining new organic photoinitiators.
11 cl, 20 cx
FIELD: organic synthesis.
SUBSTANCE: invention relates to synthesis of camptotecin analogues from 2'-amino-5'-hydroxypropiophnone corresponding to AB ring portion of camptotecin structure and tricyclic ketone converted into CDE ring portion in camptotecin structure. Preparation of 2'-amino-5'-hydroxypropiophnone comprises following steps: (1) preparing compound (b) by mixing compound (a), benzylation agent, and a base followed by stirring mixture obtained in solvent on heating under reflux; (2) preparing compound (c) by dropwise adding Grignard reagent to compound (b) under an inert gas atmosphere; (3) preparing compound (d) by mixing compound (c) with an oxidant and stirring resulting mixture; and (4) preparing compound (e) via catalytic reduction of compound (d) (see scheme 1 below). Intermediate compounds (c') and (d') are described. Also described is a method for preparing tricyclic ketone to provide efficient complete synthesis of camptotecin serving as starting compound for irinotecan hydrochloride and a various types of camptotecin derivatives as well as for stable preparation of camptotecin and its derivatives. Scheme 1: .
EFFECT: expanded synthetic possibilities in camptotecin derivatives series.
5 cl, 17 tbl, 33 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention proposes new compounds of the general formula (I):
wherein R1 means one or more similar or different substitutes taken among the group consisting of hydroxy-group, halogen atom including F, Cl, Br and J, (C1-C5)-alkyl, (C1-C5)-alkoxy-group under condition that when R1 means one substitute then it is in ortho-position and when R1 means above one substitute then at least one substitute at R1 is in ortho-position; R2 means halogen atom including F, Cl, Br and J, (C1-C5)-alkyl, (C1-C5)-alkoxy-group; R3 means halogen atom including F, Cl, Br and J; R6 means hydrogen atom or methyl; and its salts with pharmaceutically acceptable acids, hydrates or solvates. Compounds elicit activity against acne and acne-related diseases.
EFFECT: valuable medicinal properties of compounds.
7 cl, 4 tbl, 43 ex
< / BR>in which A represents C6-C10aryl, thienyl, benzothiazyl; X denotes halogen, cyano, C1-C7alkyl, trifluoromethyl, C2-C7alkoxy, or cryptometer; p is chosen from 0, 1, 2, 3, 4, or 5; Z represents a bond, -CO-NH-, SO2-NH-, a sulfur atom, sulfinyl group or a C2-C7alkenylamine radical; R1, R2, R3and E indicated in paragraph 1
-CHR8CH2CR9R10CHR11CH2- where R8and R11each H or together are - (CH2)t- where t =1; R9- H, HE, C1-C8alkyl, C1-C4alkyloxy; R10- H, C1-C8alkyl, phenyl, - (CH2)xR12where x = 0, 1, 2, 3; R12HE, C1-C4alkyloxy, - C(O)NR13R14, - NR13C(O)OR14, -SO2NR13R14, -NR13SO2R14, -NR13SO2NR14R15, -NR13C(O)NR14R15; R13, R14, R15- independently - H, C1-C4e is phenyl optionally substituted C1-C4alkyloxy, methylendioxy, Ethylenedioxy; or R7- (CH2)z- R12where z = 2, 3
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: invention concerns veterinary medicine. A vaccine contains cell suspensions of pure cultures of activators of pseudomonose Pseudomonas aeruginosa and enterococcal infection Enterococcus faecalis prepared by sampling involved organs from dead nutrias of a local epizootic centre, preparation of a suspension, inoculation for differential diagnostic mediums, recovery of pure cultures of activators and their separate cultivation in a plain broth with glucose to concentration of microbial cells 4-5 billion per 1 cm3. The vaccine also contains formalin and aluminium hydroxide in the following ratio, wt %: cell suspensions of pure cultures of the activator of pseudomonose Pseudomonas aeruginosa recovered from involved organs from dead nutrias from the local epizootic centre, in a nutrient medium with titre 4-5 billion of microbial cells per 1 cm3 - 38.0-41.5, cell suspensions of pure cultures of the activator of enterococcal infection Enterococcus faecalis recovered from involved organs from dead nutrias from the local epizootic centre in the nutrient medium with titre of 4-5 billion of microbial cells per 1 cm3 - 38.0-41.5, glucose - 2.0-1.0, formalin - 2.0-1.5, aluminium hydroxide - the rest.
EFFECT: prepared vaccine is safe, specific and immunogenic.
1 tbl, 5 ex
SUBSTANCE: invention belongs to medicine, notably to sports medicine and aeroastromedicine, and can be used in sportsmen training. For this purpose is used administration of compounds, providing increase of nitric oxide (NO) in skeletal muscles. As such a compound L-arginine may be used.
EFFECT: method allows preventing of cytosceletal proteins destruction within eccentric loads, without negative effect on cardiovascular system.
2 cl, 4 dwg