The method of producing meekatharra
(57) Abstract:The invention relates to an improved method of obtaining a known regulator of growth - meekatharra, N,N-dimethylpiperidinium. The essence of the invention is that N-methylpiperidin subjected to interaction with chloride stands at temperatures above 0oC, preferably at a molar ratio of 1 : 1 anhydrous liquid solvent, solvent N-methylpiperidin and not solvent meekathara. The preferred solvent is acetone. Separation of the final product should be carried out in the atmosphere of inert gas containing no moisture. The method allows to obtain anhydrous crystalline product containing not less than 98% of the basic substance. 4 C.p. f-crystals, 1 table. The invention relates to a method for the application of meekatharra and their specific use in agriculture.Meekathara (N, N-dimethylpiperidinium) annually is used as active ingredient for the control of excessive growth of vegetation on millions of acres of cotton, potatoes, sweet potatoes, ground nuts, grapes, corn, wheat, citrus fruits, tomatoes, ldny conditions, when the preferred one is the growth of vegetation, and not the formation of the fruit.Meekathara traditionally received in an alkaline aqueous solution (alkaline environment supported with NaOH) by attaching two methyl groups to the nitrogen atom in piperidinium ring in the result of the interaction of piperidine chloride stands at a molar ratio of methylene chloride: piperidine about 2:1 under a pressure of about 95-100 pounds per square inch. This process demetilirovania results in 50-60% aqueous solution of meekatharra. Then, to remove the sodium chloride, which is a byproduct of the reaction, to the content of 1 wt.%, is water rinsing. Then to the solution was added the dye as a means of warning the user about the danger, and antimicrobial agents are added to protect the product during storage. The resulting aqueous solution is then Packed in containers and distribute.Like all containers of pesticides (this concept includes insecticides, plant growth regulators, herbicides, and other), empty containers meekatharra must be triple rinsed and destroyed by certain about would be desirable to meekathara was in such form and in such packaging, which could reduce the time and cost of handling and disposal of containers without negative impact on meekathara.Cotton is a plant, for use where is meekathara. Meekathara retards the growth of plants of cotton, causing them to shift their forces in the direction of formation of the fruit (cotton bolls). If successful, the application of meekatharra on plants that start too aggressively grow cotton yields can be maintained or increased without deleterious effect on the plant.Cotton has a certain life cycle and certain periods of growth. Cotton seeds germinate in 7-10 days after they are planted in the furrow. The plant is cotton, which developed the root system and the growth of roots and branches, refers to "vegetating plants". The plant is cotton, which is a large part of their forces directs on vegetative growth, called "bennerstrom" cotton and generates little or no forms of cotton bolls. Cotton, which prevsitebackup. Meekathara is used to stop the rapid growth of the cotton plant by modifying the growth characteristics of plants.Branches from the main stem usually extend from opposite sides of the stem. Each fan-out segment is called "node" and is formed 5-7 node above the cotyledons before formed the first fertile escape from real leaves. The reference nodes start with the base of the plant up the main stalk. "Internode length" is the distance between fan-out segments, and a new node is formed usually every three days. For the purposes of measurement and comparison of commonly used number of nodes and internodes about 8 in order to limit the differences between fruiting plants, because fruiting branches will inevitably form on 8 nodes.Fruiting parts in cotton are called "squares". Every fruitful branch will form three fruit-bearing area ("area") approximately with the period of 6 days between education space on each branch. New square and the beginning of reproductive growth of plants of cotton called squares "pinhead" because of their barely opredelaetsa plants called "the area of match-heads". The size of match heads grow to sizes approximately middle finger and beginning of flowering early flowering").After three days under flowers are formed boxes. Approximately 30 days from the beginning of the early flowering pods ripen and can be collected. In General, approximately 80% of the total cotton crop is obtained within the first 3 weeks early flowering and 95% of the total cotton crop in 5 weeks early flowering.Usually meekathara used on cotton in one of two ways as a means to delay the growth of plants. The method used to approximately 1987 , are one-time application 8-16 oz/acre. (88-176 g/ha) 4.1% solution in early flowering. This way one treatment did not control the height of the plants, although it was noted that crop yields may decrease, especially if the plant got to stressful conditions during or after application of meekatharra.After 1987, there is a tendency to apply meekathara through a series of treatments, each of which used lower doses than after a single use. The first treatment takes place at the stage area match g is on 1 acre (0-43 g/ha), the specific dose of application depends on are plants signs of stress (no processing), differ in whether they moderate growth (approximately 2 ounces of solution per 1 acre or 21,5 g/ha) or rapid growth (approximately 4 ounces of solution per 1 acre or 43 g/ha). After this can be carried out two additional treatment with an interval of 7-14 days at doses of applications from approximately 8 oz (34 g) of 4.2% solution meekatharra using specific doses depending on the extent of vegetative growth on the treated field.Stopped in the growth of plants may have the ability to increase productivity and security boxes, but they lose the ability to further growth. However, this effect may cause a broader impact because growth ability of plants, reduction using meekatharra represent the same abilities that allow the immune system of the plant to resist disease and recover from the damage of plant tissues by insects.It would be desirable if the use of meekatharra could be integrated into the processing system, which would increase the mass the same time, limiting vegetative growth to increase fruit formation.The subject of the invention is to provide a method of producing meekatharra, which leads to the formation of solid meekatharra with high yield and with high purity. Another object of the present invention is to create a Packed form meekatharra, which eliminates the use of containers to be destroyed.Another object of the present invention is to create a system of growing cotton, which helps to increase the level of plant mass for greater resistance to disease and more rapid recovery of cotton in combination with high yield.In accordance with these and other objects of the invention which will become apparent from the description above, the method of producing meekatharra includes:
- contacting methyl chloride with N-methylpiperidine in anhydrous liquid solvent in the absence of NaOH over a period of time sufficient for the precipitation of solid meekatharra;
- separation of the above solid meekatharra from the above solvent and
- allocation of visualase is 90 wt.%.Applications of meekatharra:
a) meekathara in the form of powder with a purity of at least 98%, sealed in bag, made from a material consisting mainly of water-soluble polymer;
b) a core containing the above meekathara, and the outer layer fully covering the above solid meekathara and consisting of water-soluble polymer.System designed for growing cotton, involves the following stages:
- the use of at least one plant hormone at least one of the methods:
a) furrow at sowing cotton seeds;
b) for cotton under the first true leaves; C) for cotton under square "pinhead" and g) for cotton at the stage of early flowering;
- keeping cotton treated with at least one of the above plant hormone, to implement the vegetative and reproductive growth until the middle stage of flowering;
- the use of such a large number of meekatharra, which effectively retards the growth of cotton.Using the present invention, receive mepivacain as Evesham efficiency meekatharra, obtained in a known manner demetilirovania in the aquatic environment. Solid product form allows you to obtain the active ingredient in such formulation, which are characterized by a reduced risk of contact with the active ingredient during operation, as well as a reduced number or absence of containers that require special methods for their destruction. Each of these aspects of the invention is part of a system of cultivation of cotton, which is growing physiologically strong plants with good extraction system nutrients, so that the formation and aging of the boxes is maximum.The claimed system cotton ensures a high level of plant mass in the root system, stems, and leaves in the early growing season. Increased vegetation provides the creation of a surround system to collect nutrients and minerals the plant at the fruiting stage, when the delay of vegetation used meekathara.In accordance with the present invention meekathara receive periodic manner by: (a) probe and a temperature of approximately 0-200oC for a period of time sufficient to convert at least 90% N-methylpiperidine in solid meekathara (N,N-dimethylpiperidinium);
b) Department of meekatharra from anhydrous solvent;
in the selection above mepivacaine having a purity of at least 99%. The selected solvent can be reused in the next cycle, which increases the efficiency of the method.N-methylpiperidin is a product that can be obtained with purity of more than 98%, but which is much more expensive unit weight (~ 400%) than piperidine. However, in this process, N-methylpiperidin can be easily prometrium in anhydrous solvent with a yield of over 90% with the formation of a solid residue (100% is retained on a dense filter paper) with a purity of more than 99% without education as a by-product sodium chloride. Another advantage of the present invention is that the use of anhydrous solvents allows you to isolate the solid powder meekathara, which is more efficient per unit of weight than the aqueous product obtained in promyshlennosti with the present invention meekathara will provide a more stable control over the growing season of plants using the same doses, in comparison with meekatharra obtained in normal water process demetilirovania using NaOH to maintain an alkaline pH. Solid powder meekathara obtained in accordance with the present invention has a color ranging from white to yellow. Increased activity of the product means that a smaller amount of the active ingredient can be used to achieve the same level of control over the growth of plants or that when the same doses of the application is received more sustainable effect.Methylene chloride is a gas, and may come in contact with the liquid phase using any known method used to ensure contact of the gas/liquid, which provides an effective transition material in a gaseous state into a liquid. The simplest and most preferable for the present invention method is to use a tube is lowered below the surface of the liquid phase, and through which passes the methylene chloride. The tube is of sufficient length to ensure the dissolution of methyl chloride in an anhydrous solvent as the gas bubbles rise through the liquid. If desirable, it can be used nozzles or a big something in the reactor was about 70 psi (5 kg/cm2or less, only for reasons of economy. The use of low reaction pressure reduces the rate of the reaction vessel. Higher reaction pressure obtained at higher flow rates methyl chloride, can be used in cases where the cost of the reactor is not the limiting factor.However, it should be noted that metilirovanie N-methylpiperidine is an exothermic reaction and depends on the speed of introduction of methyl chloride. The reactor with a battery attachment usually will not require the use of a cooling system, and if the heat can naturally dissipate through the walls of the reactor. During the transition to the reactors of larger size, but should be used with some types of cooling jackets or coils placed or on the outside of the reactor or placed inside the reactor. The cooling rate and the cooling system will be selected by the engineer-chemist usually a qualification for a given feed speed methyl chloride in the process of its overall design.Reagents and receive meekathara are thermally stable. Therefore, the lower value of the range of operating temperate reaction requires temperatures above approximately 0oC. the highest value of the operating temperature is limited by a combination of evaporation temperature anhydrous solvent and pressure at which the calculated reactor. If the anhydrous solvent is acetone, the preferred temperature is about 70oC and below, with the most preferred temperature is in the range of approximately 40-50oC to ensure a working temperature changes during the monitoring process.Anhydrous solvents that can be used as a medium in the present invention are such solvents are:
(a) in which N-methylpiperidin and methylene chloride soluble at the same time;
b) which do not interact with N-methylpiperidine and chloride stands and
(C) in which meekathara insoluble. Examples of such solvents are, among others, acetone, methyl ethyl ketone, toluene, benzene, and methylene chloride. Acetone is a particularly preferred solvent.Because meekathara is not soluble in the solvent, the solid product can be separated from the anhydrous solvent using conventional equipment. Examples of acceptable equipment is nabunya suitable filtering material, and plate and frame filters. Preferably, the filtration equipment was made of korrozoustoychivost material, such as stainless steel. Rinsing with acetone in the process of separation of the solid product will help to remove any amount of unreacted N-methylpiperidine.Similarly, the product may be dried using any equipment intended for the drying of the solid products. Especially preferred vacuum drier, made of stainless steel or lined with glass carbon steel.As a powder meekathara very hygroscopic, contact with moisture or atmosphere saturated with moisture must be excluded in order to prevent sliianie or dissolution of the product. All stages - separation, drying, retseptoriani and packaging should be carried out in an inert atmosphere at a relative humidity, which should be as low as possible. Preferably, all working stage on which the solid meekathara may be subjected to atmospheric or other moisture was carried out under a layer of nitrogen, although there may be used any inert gases, or carbon dioxide.One form of application of high-purity solid meekatharra, which follows from this way to obtain is to package the powder in a bag of water-soluble material. Examples of such materials are polyvinyl alcohol (PVA), polymers, cellulose derivatives such as methylcellulose, hydroxypropylcellulose, hypromellose and their mixture. Particularly preferred form of application, which consists of an inner bag made of PVA, enclosed in a bag of aluminum foil. The bag from the foil is opened so that the inner bag of PVA can be lowered into the tank or reservoir containing water, resulting after the dissolution of the PVA meekathara is released into the tank.Another embodiment of the present invention is that solid medicalhistory layer or coating so to the pellet or tablet were completely isolated. Examples of materials suitable for encapsulation, are polyvinyl alcohol, polymers, cellulose derivatives such as methylcellulose, hydroxypropylcellulose, hydroxymethylcellulose and their mixture.If desired, meekathara in the form of a powder may be suspended in a suitable anhydrous solvent or a binder substance and jointly subjected to extrusion together with external kapsulirujushchej layer in order to obtain dispersed particles meekathara. Suitable kapsulirujushchej materials are, for example, polyvinyl alcohol, polymers, cellulose derivatives such as methylcellulose, hydroxypropylcellulose, hypromellose, and mixtures thereof.Regardless of the specific method of packaging to the finished shape can be added one or more auxiliary substances. Examples of suitable excipients include water-soluble solid dye to warn consumers that spilled solid product or prepared aqueous solution contains meekathara. Acceptable dyes are dyes that have been approved as inert phrases is the FL, and listed in the Code of Federal Regulations governing their use, for example: FD&C blue No. 1; Rhodamine B; methylene blue; methylthiomethyl 2B; and red dye No. 17, 40, 48. Due to good visibility in aqueous solutions are particularly preferred red and blue dyes.If it is desirable, as a means of warning accidental or intentional ingestion of solid product, may be added as solids, restraint from eating or emetic agent. A particularly effective substances, restraint from eating, are plant materials of the Cucurbitaceae family, for example, powder of roots of Buffalo gourd "(buffalo gourd). To the product in the form of briquettes or pellets may be added blowing agent, for example, sodium bicarbonate, in order to facilitate the dissolution and mixing after the release of product to the spray tank or reservoir.In General, there is no need to add to meekatharra additives such as a dispenser on a surface or adhesive, although their presence will not adversely impact on the ability of meekatharra delay R is hetzii plants of cotton, as usual the product obtained in the process water methylation, although somewhat fewer meekatharra of the present invention is necessary in order to achieve the same level of control over the growth of plants. Usually the dose of meekatharra up to approximately 30 g/acre (12.4 g/acre) for individual doses within the range from about 2.5 g/acre (1.0 g/ha) to apply 2 ounces-acre of 4.2% solution to 10 g/acre (4.1 g/ha) to apply 8 oz/acre same as 4.2%-aqueous solution. The dose of meekatharra of the present invention will be slightly lower (for example, about 90-98%) than normal dose application, to achieve the same level of stunting.Crops on which meekathara and meekathara of the present invention can be used are cotton, potato, sweet potato, groundnut, grapes, corn, wheat, citrus fruits, tomatoes and onions.One of the special aspects of the present invention is to create a system of growing cotton, which involves sowing seeds in the furrow, the use of plant hormone containing fertilizer, in furrow around the seeds and the seeds, virusiv is taniam dose, sufficient to delay growth. This combination of stages increases the growth of plants in the early stages and increases the weight of the plants (especially roots and stems), which leads to an increase in the education and preservation of fruits. Subsequently, further vegetative growth is delayed with meekatharra, which contributes to the formation of the fruit (bolls). However, because plant growth was accelerated in the early stages of the growing season, the plant absorbs large quantities of nutrients, resulting in the immune system of plants has a higher ability to resist disease and recover from damage by insects and withstand drought.The plant growth regulators that can be used in the present invention and which can be used separately or in combination, are those tools that enhance and support the growth of plants. Examples of plant growth regulators are at least one of the 84 identified gibberellins, preferably for the present invention GA3, GA4, GA5, GA7and GA9, cytokinins (e.g., zeatin, kinetin, benzyladenine, digitization and isopentenyl (NUS), ortho-nitrophenolate sodium para-nitrophenolate sodium, 5-nitroguaiacol sodium and polygalacturonase acid containing 2, 4, 5 and 6 carbon atoms. These plant growth regulators affect and change metabolicheskie processes in plants that accelerates their growth. All these tools can be used in the doses given in the product's labeling.As it turned out, meekathara acts as a hormonal agent against plant growth to retard the growth after some opposition or interference with plant hormones. Therefore, the cultivation of cotton in accordance with the present invention increases the growth of plants in the early stages by the addition of plant growth regulators in the soil around the seed and/or vegetative plants to compensate for later intervention in the cycle plants meekatharra.Many of the commercially available fertilizers and means of regulating the growth of plants, contains plant growth regulators. For use in the present invention is particularly preferred astragulus tool offered by Micro Flo Company of Lakeland (USA, Florida) under the trade name of PGR-IVthat content is cotton PGR-IVinvolves the use of expenditure rate corresponding to the rate of flow of less than 20 g/acre (8 g/ha), preferably less than 1 g/acre (0.4 g/ha), and most preferred consumption rate lies in the range of about 30-300 mg/acre (12-121 mg/ha) plant growth regulator.In accordance with the present invention meekathara used for processing plants of cotton in the middle stages of flowering, although it is possible to conduct earlier treatment for specific plants showing early signs of rapid growth. The middle stage of flowering can be easily determined with the help of two tests characterizing the same period:
a) 10 days after the appearance of the 5 white boxes on the segment number 25 feet (7.6 m) or
b) the average internode length of about 3 inches (76 mm), which is measured on the four upper fully formed nodes of the plant. In the middle stages of flowering meekathara used in the dose 4-16 oz (118-473 ml) 4,2%-aqueous solution, which corresponds to the dose of meekatharra 5-20 g per acre (4,1-16.7 g/ha). If not achieved the required reduction in plant growth, it may be repeated treatment with the same standards of consumption, while the consumption rate will not exceed peblisa on 1 acre.Example 1
Meekathara receive periodic way, loading into the reactor 4 liters of acetone. Then the solvent is added to 1000 g of N-methylpiperidine, and the reactor sealed. Through the immersion tube is lowered below the surface of the liquid in the reactor, within 2-6 hours to enter 510 g of methyl chloride (10% mol. ) excess). The feed rate of methyl chloride is controlled so that the pressure does not exceed 70 psi (5 kg/cm2and remained in the range of values for which the calculated reactor. The reaction mass was incubated over night so that the full cycle is 24 hours, More than 95% of N-methylpiperidine becomes meekathara, which precipitates to the bottom of the reactor.Solid meekathara separated from the acetone (which after separation of the re-used) by filtering. To remove any absorbed impurities used washing with acetone. Solid meekathara dried using vacuum filtration and receive a product having a purity of over 99.5%;
The ratio used in this example correspond to the molar ratio of methyl chloride to N-methylpiperidino of 1.1:1. In industrial operations, when together with a dedicated restot be considered as a minimum for maximum conversion moreover, the molar ratio of methylene chloride : N-methylpiperidin is at least 1:1, preferably from 1.05:1 to 1.5:1.Example 2
Solid meekathara dissolved in water, receiving, 4,2% solution, and compared with 4.2% aqueous solution, which is sold under the trademark PIX. It is assumed that the PIX prepared in the usual way demetilirovania pyridine in aqueous medium under alkaline conditions, supported with NaOH.Comparative experiments were conducted on a statistically sufficient number of cotton plants under controlled growing conditions. Active ingredient (AI) applied on the foliage of the cotton plants at the stage area of match heads in doses corresponding to 5 g/acre (12.5 g/ha) and 10 g/acre (25 g/ha). This period of the growing cycle of the cotton plant selected in order to determine any differences in the effects with cotton at the stage of rapid growth.Designation RP corresponds to the solution of meekatharra obtained from soluble powder meekatharra received in accordance with the present invention. The results presented in the table.From the results of the table shows that the solutions of meekatharra, preparation, irout the height of the plant above node 8 is better than commercially available product, which probably made using the method of water methylation. 1. The method of producing meekatharra, comprising contacting N-methylpiperidine chloride stands in the presence of a solvent at a temperature above 0oC and pressure with subsequent isolation of the target product, characterized in that the solvent used is anhydrous liquid solvent in which insoluble meekathara and soluble N-methylpiperidine, and the process is continued until precipitation of the final product, which is separated from the solvent by filtration and was isolated with a purity of at least 98%.2. The method according to p. 1, characterized in that the solvent used is acetone.3. The method according to PP.1 and 2, characterized in that the process is conducted at a molar ratio of methylene chloride: N-methylpiperidin not less than 1:1.4. The method according to p. 1, characterized in that the selection of meekatharra with 99.5% purity is carried out by washing with acetone and drying.5. The method according to p. 1, characterized in that the separation of meekatharra from the solvent and its allocation is carried out in an atmosphere containing no moisture.
FIELD: organic chemistry, chemical technology, medicine, pharmacy.
SUBSTANCE: invention relates to a new biologically active compound. Invention describes quaternary ammonium derivative of lidocaine of the formula:
eliciting anti-arrhythmic activity. Also, invention describes a method for preparing quaternary ammonium derivative of lidocaine of the formula (1). Method involves interaction of N-(2,6-dimethylphenylaminocarbonylmethyl)-morpholine with allyl bromide in isopropyl alcohol medium at temperature 58-62°C followed by cooling the reaction mixture to room temperature and isolation of N-allyl-(2,6-dimethylphenylaminocarbonylmethyl)-morpholinium bromide. Invention provides preparing new compound eliciting useful biological properties.
EFFECT: improved preparing method.
2 cl, 4 tbl, 4 ex
FIELD: chemistry of metalloorganic compounds, agriculture.
SUBSTANCE: invention describes derivatives of mepiquate borate of the general formula (I): wherein DMP means N,N-dimethylpiperidinium (mepiquate); M means metal cation acceptable for agriculture and chosen from a series comprising sodium, potassium, magnesium, calcium, zinc, manganese or copper, hydrogen atom or NH4 +; O means oxygen atom; A means chelate of complex-forming fragment bound with one boron atom and representing (lower)-alkylglycols or sugars; n and m mean similar whole numbers in the range from 1 to 6; x means a whole or fraction number in the range from 0 to 10; y means a whole or fraction number in the range from 1 to 48; z means a whole or fraction number in the range from 0 to 48; v means a whole or fraction number in the range from 0 to 24, and w means a whole or fraction number in the range from 0 to 24. Also, invention describes methods for preparing compound of the formula (I) by interaction of N,N-dimethylpiperidinium hydroxide with boric acid and/or boron-containing oxides and optionally with metal hydroxides acceptable for agriculture indicated above or electrochemical method involving interaction of N,N-dimethylpiperidinium halide in the presence of water and boric acid and in the presence metal hydroxides acceptable for agriculture by bipolar electrodialysis. Invention describes electrochemical method for preparing N,N-dimethylpiperidinium hydroxide and a suspension concentrate possessing the plant growth-regulating effect prepared by mixing N,N-dimethylpiperidinium hydroxide, boron-containing compound chosen from boric acid and borate salt with a thickening agent and water, or by mixing compound of the formula (I) with Na2B8O13 x 4 H2O, a thickening agent and water. Prepared derivatives of mepiquate borate possess the improved indices of hygroscopicity and corrosion activity.
EFFECT: improved preparing methods, valuable properties of derivatives.
22 cl, 7 tbl, 16 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to compounds of (R)-2-arylpropionamide of the formula (I): , wherein Ar means aryl of the formula (IIIb): F-Arb wherein Arb means phenyl mono- or poly-substituted with the following groups: chlorine, fluorine atom; F means hydrogen atom, linear or branched (C1-C5)-alkyl residue, benzoyl, 2,6-dichlorophenylamino-, 2,6-dichloro-3-methylphenylamino-group; R means hydrogen atom, (C1-C4)-alkyl; X means linear or branched (C1-C6)-alkylene optionally substituted with the group -CO2R4 wherein R4 means hydrogen atom or linear or branched (C1-C6)-alkyl group, phenyl or phenylmethylene group; R1, R2 and R3 mean independently linear or branched (C1-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C6)-alkenyl, aryl, aryl-(C1-C3)-alkyl, or R1 and R2 in common with nitrogen atom (N) to which they are attached form nitrogen-containing 6-membered heterocyclic ring of the formula (II) , and R3 has values indicated above independently wherein in the formula (II) Y means a simple bond, methylene group, oxygen atom, nitrogen atom or sulfur atom; p means a whole number 2; Z- means a pharmaceutically acceptable counterion of quaternary ammonium salts. Also, invention relates to using compound of the formula (I) in treatment of psoriasis, pemphigus and pemphigoid, rheumatic arthritis, intestine chronic inflammatory pathology including ulcerous colitis, acute respiratory distress-syndrome, idiopathic fibrosis, mucoviscidosis, pulmonary chronic obstructive disease and glomerulonephritis, and also for prophylaxis and treatment of injure caused by ischemia and reprefusion. Also, invention relates to a pharmaceutical composition possessing the inhibitory activity with respect to chemotaxis of polymorphonuclear leukocytes and monocytes induced by complement C5a fractions and comprising compound of the formula (I) in mixture with a suitable carrier. Also, invention relates to a method for synthesis of compounds of (R)-2-arylpropionamide of the formula (I) that involves interaction of amides of the formula (IV) given in the invention description with compounds of the formula R3Zwherein Z means a leaving group, such as chloride, bromide, iodide, methanesulfonate, p-toluenesulfonate, sulfate. Invention provides synthesis of (R)-2-arylpropionic acid omega-aminoalkylamide quaternary ammonium salts used for inhibition of chemotaxis activation induced by the C5a complement component.
EFFECT: valuable properties of compounds and pharmaceutical compositions.
17 cl, 1 tbl, 6 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to application in an effective amount and to new nicotine receptor agonists described by general formula (i) or (ii) for treating inflammatory diseases chosen from a group including asthma, chronic obstructive pulmonary disease (COPD), interstitial pulmonary tissue fibrosis (IPF), sarcoidosis, hypersensitivity pneumonitis (HP), chronic hypersensitivity pneumonitis and bronchiolitis obliterans organising pneumonia (BOOP). The compounds (i) and compounds (ii) relate to formulae (i) (ii) where in formula (i) R1 and R2 independently mean alkyl with 1-10 carbon atoms; Xa means CH or N; Ya means one or more substitutes chosen from hydrogen, halogen, cyano, hydroxyl, alkyl with 1-10 carbon atoms optionally substituted with one or more halogen atoms, and alkoxy with 1-10 carbon atoms; n means an integer 0 or 2; J means a counterion representing a compound for maintaining electric neutrality, e.g., halogen, sulphate, sulphonate; in formula (ii) R3 is chosen from or Xb means N or N+-R10; R4 means one or more substitutes chosen from hydrogen, halogen; each R10, R11 and R12 independently means alkyl with 1-10 carbon atoms; provided the presence of the counterion when Xb means N+-R10.
EFFECT: use of nicotine receptor agonists in the effective amount for treating inflammatory diseases.
26 cl, 40 dwg, 3 tbl, 38 ex