4-methylanilide-n-n-propylpyrrolidine-2-carboxylic acid borate, having anthelminthic activity
SUBSTANCE: invention relates to a novel compound 4-methylanilide-N-n-propylpyrrolidine-2-carboxylic acid borate of formula:
, having anthelminthic activity. The compound is obtained through bromination of 5-chlorovaleric acid with subsequent conversion thereof into an acid chloride using thionyl chloride, further amination with 4-methylaniline and then ring closure with n-propylamine in 4-methylanilide-N-n-propylpyrrolidine-2-carboxylic acid and reaction of the latter with boric acid.
EFFECT: high activity of the compound.
The claimed connection relates to the field of organic chemistry class arylamido azacyclopentadecan acids, namely new biologically active 4-methylaniline-N-n-propylpyrrolidine-2-carboxylic acid borate (I) of the formula:
which can be used as an anthelminthic drug drug.
As standards anthelminthic action used a well-known drugs Pyrantel and levamisole [Mashkovsky PPM Medicines. - 15-ed., Rev., Corr. and supplementary): RIA "New wave": the Publisher Merenkov, 2008. - 1206 S.: ill.].
The aim of the invention is to obtain a new previously undescribed 4-methylaniline-N-n-propylpyrrolidine-2-carboxylic acid borate having anthelmintic activity. This goal is achieved by the synthesized δ is haralanova acid, followed by its translation into the acid chloride with chloride tonila, further aminating 4-methyl-aniline production and then cyclization with n-Propylamine 4-methylaniline-N-n-propylpyrrolidine-2-carboxylic acid and the interaction of the latter with boric acid according to the scheme:
Synthesis of base 4-methylaniline-N-n-propylpyrrolidine-2-carboxylic acid made by well-known methods [Lihosherstov A.M., Pryanishnikova HT., Lebedev, A.S., and other Azacycloheptane XIX. Synthesis and an anaesthetic activity of some Mezhidov pyrrolidinecarbonyl-2 acid. // Chem-Pharm. J., 1976, Vol.7, p.36-40.].
Borat 4-methylaniline-N-n-propylpyrrolidine-2-carboxylic acid
Mixed 0.04 mol of 4-methylaniline N-propylpyrrolidine-2-carboxylic acid in 15 ml of ethanol and 0.08 mol of boric acid in ethyl alcohol (in sufficient quantity to dissolve when heated). Then was placed in a round bottom flask of 100 ml with a reflux condenser and heated on a water bath for 15 minutes After evaporation of the solvent precipitated residue, which is recrystallized twice from acetonitrile. The yield was 56%, TPL 196-198°C, the decomposition of 310°C.
The inventive compound is a white crystalline substance or plate white color, soluble in ethanol, DMF, with water forms an emulsion milky white, not soluble in acetone, hexane, diethyl ether. The NMR spectrum1N (BS-567A, (100 MHz) in CDCl3internal standard - GMDS) of compound (I) include: a triplet of three protons metal group through radical at the nitrogen heteroatom when 0,890 ppm, multiplet two protons of methylene group through radical at the nitrogen heteroatom when 1,475-1,707 ppm, multiplet four protons of two methylene groups pyrolidine cycle when 1,929-2,244 ppm, a singlet of three ol the tones of a methyl group to the aromatic ring at 2,244 ppm, multiplet three methylene protons and CH-groups pyrolidine cycle and two protons of methylene group have various substituent at the nitrogen heteroatom at 2,800-4,072 ppm, multiplet four protons of the aromatic ring in the area 6,242-7,438 ppm, a singlet proton-NH-group at 9,386 ppm, a singlet proton boric acid at 10,258 ppm
Study of biological activity
Anthelmintic activity was studied on earth (rain) worms (Lumbricus terresrtis) according to the method of Nikolaev M.P. (1941): in a 0.5% aqueous solution of tested compound was placed earthworms and recorded the time of death. As standards of comparison used a 0.5% aqueous solutions of Pyrantel (as pamoate) and levamisole.
Acute toxicity when administered orally (p/o) was determined by nonlinear white mice of both sexes weighing 18-24 g test substance and the Comparators was introduced through the mouth using a probe in the form of aqueous solution or suspension (for Pyrantel of pamoate, because it is not soluble in water) at a rate of 0.1 ml / 10 g weight of the animal in increasing doses. The results were processed by Prozorovsky calculation of the median lethal dose (LD50) at P≤0,05 [Prozorovsky CENTURIES, Prozorovsky BTW, Demchenko V.M. Pharmacol. toxicol., Vol 41, No. 4, s-502, 1978.]. The results of anthelmintic activity and acute toxicity of the compounds I, the feast of the body and levamisole are presented in table 1.
|Connection||The lifespan of worms, min||P1in comparison with Pyrantel||P2in comparison with|
As can be seen from the table, the inventive compound of formula (I) 18.3 times is less toxic in comparison with levamisole and significantly greater in anthelminthic activity of 1.85 times. In addition, the compound of formula (I) toxicity is comparable to the toxicity of Pyrantel (a drug with low toxicity), but significantly greater in anthelmintic action in 49.3 times.
Thus, 4-methylaniline-N-n-about iparralde-2-carboxylic acid borate exhibits more pronounced anthelminthic effect at equal or lesser toxicity, what Pyrantel and levamisole. Therefore, the claimed compound (I) can be used in medicine as an anthelmintic drug.
4-methylaniline-N-n-propylpyrrolidine-2-carboxylic acid Borat
having anthelmintic activity.
SUBSTANCE: invention relates to novel compounds of formula or to its pharmaceutically acceptable salts, where n is 0 or 1; R1 represents H or F; R2 represents C1-4alkyl; R7 represents H or C1-4alkyl; and Z represents hydroxyl C1-6alkyl or C1-6alkoxycarbonyl, or 5- or 6-member heteroaromatic ring, which belongs to aromatic rings which have given number of atoms, of which at least one is N, O or S, the remaining being carbon atoms, and which also optionally has methyl substituting group. Invention also relates to pharmaceutical composition, to application of compounds, as well as to method of obtaining formula I compounds.
EFFECT: obtaining novel biologically active compounds, possessing activity of receptor 5-HT2A antagonists.
9 cl, 25 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to derivatives of nitrogen-containing heterocyclic compounds of the general formula (I'):
wherein R represents the group:
m = 0-3; R1 represents halogen atom, cyano-group and others; X represents oxygen or sulfur atom, or the group -CH2 and others; Z1 and Z2 represents the group -CH2 and others; Q represents oxygen or sulfur atom, or the group -CH2 or -NH; R2 represents substituted phenyl; n = 0-2; R3 represents (C1-C6)-alkyl, (C1-C6)-alkoxycarbonyl group and others; R4, R5, R6 and R7 represent hydrogen atom or (C1-C6)-alkyl and others; R8 represents hydrogen atom, (C1-C6)-alkyl. Compounds of the formula (I') possess of activity modulating activity of chemokine MIP-1α receptors and can be used in medicine in treatment of inflammatory diseases and respiratory ways diseases.
EFFECT: improved preparing method, improved methods for treatment, valuable medicinal properties of compounds and composition.
20 cl, 283 ex
SUBSTANCE: invention refers to medicine and aims at treating the patients suffering acute viral hepatitis B and mixed hepatitis (B+C, B+D, B+C+D). A basic therapy is involved. The perfluorocarbon emulsion Perftoran is introduced intravenously drop-by-drop. The dose is 400 ml 1-2 times a day for 2-3 days, in a therapeutic course of 800-2400 ml. It is added with the following complex pathogenetic therapy. 0.5% Novocaine 20-25 ml intravenously drop-by-drop once a day; 5% ascorbic acid 2 ml intramuscularly twice a day; 10% a-tocopherol in oil 1 ml intramuscularly twice a day; 5% unitiol 5 ml intramuscularly twice a day; N-acetylcystein 10 mg/kg per os twice a day; retinol 5000 IU in capsules per os after meal twice a day; 5% mexidol 2 ml intravenously. The length of treatment is 10 days.
EFFECT: method provides higher therapeutic effectiveness, reduced length of hospital treatment and costs.
8 tbl, 2 ex, 2 cl
FIELD: pharmaceutical industry.
SUBSTANCE: invention relates to a complex for the antimicrobial and / or anti-inflammatory action, which contains fulvic acid having a molecular weight not exceeding 20 kDa herewith fulvic acid derived from sugar. The complex can also contains aluminum, mercury, cadmium, chromium and lead in amounts which do not harm human body. The invention also relates to a method of producing the specified complex which comprises dissolving the carbohydrate to form of a solution and oxidation of this carbohydrate in the water vapor. The obtained product, containing acidic components is subjected to filtration to remove acidic components with a molecular mass greater than 20 kDa.
EFFECT: invention provides complexes of fulvic acid, which practically does not contain harmful elements such as aluminum, chromium, mercury, other, and can be safely used in the pharmaceutical industry.
26 cl, 2 dwg, 1 tbl, 4, ex
SUBSTANCE: group of inventions refers namely to dermatology and can be used for prevention and treatment of the pustulous diseases caused by bacterial skin defeats. For this purpose the damaged skin amazed and adjoining areas are worked with the antiseptic of "Likvacid" received with the use of trinol by means of its preliminary dissolution in a dimethyl sulfoxide in the ratio 1 mas.h. to 0,9 mas.h., accordingly, at the temperature not below indoor temperature before dark blue coloring of a mix occurs, and mixture then with a filler based on alcohol with addition of glycerin and further filtration of the received mix, herewith using as a filler of a solution of acid in ethyl spirit with its initial concentration accepted that the end-product has not less than 70 %, and with a choice of all components in the following ratio, mas.: trinitrotoluene- 0,25-1,5, a dimethyl sulfoxide - 1,0-10,0, acid - 0,5-1,0, glycerin - 17,5-23,0, ethyl spirit - the rest. The skin is greased with a wadded tampon with frequency of 2-3 times a day. Thus duration of therapy is not less than 17 days and to epulosisof the damaged surface. Or in case of the second invention grease the damaged skin and adjoining areas are greased with a wadded tampon with frequency of 2-3 times a day. The therapy course is not less and in addition is accepted than 10 days by taking "Likvacid" per oral 2-3 times a day within no more than 10 days. Herewith adults people take 11-16 ml, young men to 18-year-old age - 5-10 ml.
EFFECT: the use of the given inventions allows carrying out effective preventive maintenance and treatment in case of optimum terms of therapy.
2 tbl, 1 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to veterinary gynaecology. A preparation for treating acute postnatal endometritis in cows involves antimicrobial and antiprotozoal agents, and as the antimicrobial agent the preparation contains enrophlone, as the antiprotozoal agent - trichopol (metronidazole), in addition, the preparation contains DMSO, sodium hydroxide and distilled water in the following proportions, g/l of the solution: enrophlone 8.0-12.0; trichopol (metronidazole) 4.0-6.0; DMSO 150.0-250.0; sodium hydroxide pH 10-11; distilled water - the rest. The method of treating acute postnatal endometritis consists in introduction of the specified preparation 50-100 ml once a day for 3-5 days.
EFFECT: invention provides higher clinical effectiveness.
2 cl, 2 ex
SUBSTANCE: present invention refers to medicine, namely neurology, and can be used for treating patients with trifacial nerve neuralgia. For this purpose, a drug-induced therapy used to stimulate a re-myelination process is added with applications of tissues wetted in a solution consisting of mixed drugs taken in the following proportions, %: 98% dimethyl sulfoxide solution - 20, 2% lidocaine solution - 40, 2% alcoholic solution of benzocaine - 40. Length of daily applications is 30-45 minutes every 3-4 hours 4-5 times a day. The therapeutic course is 7-10 days.
EFFECT: method allows providing higher clinical effectiveness ensured by prolonged remission and fast pain syndrome management.
SUBSTANCE: invention relates to medicine, namely to ophthalmology, and can be used for treatment of infectious keratitis. For this purpose method includes application of polyoxidonium solution, which is prepared from 6 mg of polyoxidonium per 5 ml of 5% dimexide solution. Solution is introduced by bath electrophoresis one time per day from anode with current intensity, starting with 0.3 mA, increasing it with each following day by 0.1 mA. Duration of the first procedure constitutes 8 minutes, with 1 minute increase every day. Course of treatment consists of 6-10 daily procedures.
EFFECT: method ensures reduction of terms of cornea inflammation relief with reduction of disease recurrences, as well as reduction of complications of disease and performed therapy.
2 ex, 1 tbl
SUBSTANCE: invention refers to medicine, particularly to oncology, and can be applied in treating rectal cancer (RC). A method involves the intrarectal introduction of 5-fluorouracil and metronidazole in a composite mixture containing sodium alginate and 2 % dimethylsulphoxide, beam therapy, local SHF hyperthermia followed by a surgical intervention. 5-fluorouracil is introduced daily from the 1st to 5th day, and from the 3rd and 5th days of the therapeutic course, 5-ftoruratsil is introduced in a combination with metronidazole with the exposition 5 hours, and the surgical intervention follows in 2-3 weeks after the therapeutic course.
EFFECT: use of the invention allows increasing recurrence-free survival rate in the RC patients.
FIELD: medicine, pharmaceutics.
SUBSTANCE: composition for colonic diseases containing a polymeric base in the form of sodium alginate and Dimexidum in the amount 6-9% is offered. The invention can be used for treatment of the terminal colonic diseases, namely hemorrhoids, rectal inflammation, proctosigmoiditis, rectal fissures, and also for prevention and treatment of radiation complications in rectal and urogenital cancers.
EFFECT: evident therapeutic effect of Dimexidum in synergetic action of the ingredients of the composition with no side complications after a prolonged 4-8-hour contact of an affected region of mucosa with the preparation is shown.
FIELD: medicine, veterinary.
SUBSTANCE: group of inventions relates to animal feeding. It includes composition, which contains from approximately 0.9% to approximately 1.5% of methionine, from approximately 1200 to approximately 5000 mln-1 of taurine, from approximately 120 to approximately 450 mln-1 of vitamin C, and from approximately 700 to approximately 2000 IU/kg of vitamin E, method of improving antioxidant status of animals, by feeding them said composition and application of said composition.
EFFECT: group of inventions results in improvement of antioxidant status of animals, in particular, to reduction of prooxidants number in animal blood, improvement of animal blood ability to absorb oxygen radicals, increase of number of antioxidants in animal blood and reduction of damaged DNA in animal.
34 cl, 6 tbl, 2 ex
SUBSTANCE: invention refers to medicine, namely to functional diagnostics. Capillaroscopy of nail-bed vessels of both fourth fingers is involved prior to and after pharmacological tests. A first pharmacological test is conducted by application of a mediator containing adrenaline in concentration 10-5 mol/l mixed with dimethyl sulfoxide taken in the ratio 1:1 on one hand. Vasoconstriction time t1 and vascular tone recovery time t2 are determined. The mediator is removed by wiping a nail bed with 70% ethanol. A second pharmacological test is conducted by application of a mediator containing acetylcholine in concentration 10-5 mol/l mixed with dimethyl sulfoxide taken in the ratio 1:1 on the other hand. Vasodilatation time t3 and vascular tone recovery time t4 are determined. The mediator is removed by wiping a nail bed with 70% ethanol. If the value t1 is 2 to 5 seconds, t2 is 20 to 44 seconds, t3 is 8 to 15 seconds and t4 is 16 to 25 sec, the degree I PHD is diagnosed, while the values t2 45 to 65 seconds and t4 10 to 15 sec enables to diagnose the degree II PHD.
EFFECT: technique allows improving diagnostic accuracy of the PHD severity in miners that is ensured by detection of endothelial dysfunctions directly in local vibration action points.
1 tbl, 2 ex
SUBSTANCE: method involves carrying out X-ray examination with radiopaque substance being used. Biologically inert flexible cups for porolon inlay to be placed congruently to gingiva contour. The inlay is impregnated with Dimexid and left in oral cavity for 30-40 min before making X-ray examination.
EFFECT: high accuracy of diagnosis.
SUBSTANCE: method involves applying napkin impregnated with medicament to an injured articulation area. The medicament contains hydrocortisone acetate in the amount of 0.4mg/cm2, dimexide - 1.4 mg/cm2 and sodium alginate - 4.1 mg/cm2. The napkins are applied to internal and external side of the articulation for 6 days, changing them in three days.
EFFECT: accelerated treatment course.
FIELD: medicine, dermatology, cosmetology.
SUBSTANCE: the present innovation deals with treating inguinal diseases. For this purpose at the first stage one should removed detached or hypertrophied layers of inguinal horn cells due to layer-by-layer polishing with drill's diamond head to detect pathological defects in inguinal layers or under the nail or their removal or straightening. Then comes interval during 3-7 d. At the second stage one should remove redetached layers followed by another interval for 3-7 d. Polishing stages of detached layers should be carried out till restoration of nail matrix growth towards its free edge, moreover, it is necessary to smooth and polish inguinal surface with manicure filing. Moreover, one should apply dimexide lotions during therapy. The innovation leads to quick and valuable inguinal restoration due to keeping the bond of nail matrix, nail bed, and subunguinal matrix at carrying out restorative stages of inguinal growth.
EFFECT: higher efficiency of restoration.
3 ex, 1 tbl
SUBSTANCE: according to the availability of characteristic features, such as asymmetry of blepharolinkage from the right and from the left, the shift of one shoulder blade against vertebral column, asymmetry of either right or left shoulder in horizontal plane, the difference in the tonicity of rectus muscles of the back and their painfulness at palpation from the right and from the left by taking into account sexual differences in the frequency of domination of one of cerebral hemispheres one should detect a painful point to introduce 50%-analgin solution into it at the volume of 0.2-2.0 ml for the depth of 5-15 mm.
EFFECT: shortened terms of therapy.
FIELD: medicine, surgery.
SUBSTANCE: method involves carrying out an antibacterial therapy and additional administration of curative mixture consisting of one part of dimexide, two parts of 0.5% of novocaine solution with antibiotic eliciting high the bacteriostatic activity against microflora in duct secret. Administration of this curative mixture is carried out by catheter into injured duct directly by course 1-2 times. Invention promotes to topical sanitation of mammary gland duct and reducing time of disease. Invention can be used in treatment of galactophoritis.
EFFECT: improved method for treatment.
FIELD: medicine, arthrology, pharmacy.
SUBSTANCE: agent comprises glucosamine salt as saccharide, dimethylsulfoxide, ointment base and ibuprofen or nimesulide, or piroxicam, or meloxicam, or diclofenac salt, or indometacin, or ketoprofen as a nonsteroid anti-inflammatory agent. Glucosamine hydrochloride, glucosamine sulfate sodium, potassium or calcium salt is used as glucosamine, and diclofenac potassium or sodium salt is used as diclofenac salt. New ointment shows high perfusion rate of active substances to the articulation zone and enhanced effectiveness. Invention expands assortment of agents used in treatment of articulations.
EFFECT: improved, enhanced and valuable medicinal properties of agent.
2 cl, 14 ex
FIELD: veterinary science.
SUBSTANCE: the suggested preparation contains the following ratio of components, weight%: dioxidine 0.48-0.52, furacrylin 0.021-0.027, dimethylsulfoxide 38-50, distilled water - the rest.
EFFECT: higher therapeutic efficiency.
3 ex, 3 tbl