30 results about "Parecoxib" patented technology

The invention discloses a method for preparing Parecoxib. The method for preparing the Parecoxib comprises the following steps of: performing sulfonation reaction on 1,2-diphenyl butanone serving as a raw material to obtain 1-phenyl-2-(4-sulfo phenyl)butanone; in the presence of alkali, performing condensation on the 1-phenyl-2-(4-sulfo phenyl)butanone and acetylchloride to prepare 1-phenyl-2-(4-sulfo phenyl)-2-acetyl butanone; performing cyclization on the 1-phenyl-2-(4-sulfo phenyl)-2-acetyl butanone and hydroxylamine hydrochloride to obtain 4-(5-methyl-3-phenyl-4-isoxazole)benzenesulfonic acid; performing chlorination and ammonolysis reaction to prepare Bextra; and reacting the Bextra with propionic anhydride to synthesize the Parecoxib. In the method, the raw materials are readily available and reaction conditions are not rigorous. The method is easy and convenient to operate and has certain industrialized value.

The invention relates to the technical field of medicine analysis, and particularly relates to a reversed-phase high-performance liquid chromatography (RT-HPLC) detecting method for valdecoxib / parecoxib related substances. The RT-HPLC detecting method includes preparing an analysis solution, determining chromatography conditions and detecting in an instrument. The method can effectively detect existence of the related substances in valdecoxib and parecoxib solutions, particularly separates the characteristic peak of the valdecoxib, the characteristic peak of a valdecoxib isomeride and the characteristic peak of meta valdecoxib in a spectrum, and particularly separates the characteristic peak of the parecoxib, the characteristic peak of a parecoxib isomeride and the characteristic peak of meta parecoxib in a spectrum, thus ensuring quality controllability of products.

A parecoxib preparation method comprises the following steps: reacting diacetophenone oxime with ethyl acetate in a lithium diisopropylamide / tetrahydrofuran system to generate 4,5-dihydro-5-methyl-5-hydroxy-3,4-dibenzylisoxzzole; reacting 4,5-dihydro-5-methyl-5-hydroxy-3,4-dibenzylisoxzzole with halogenated sulfonic acid, and ammonolyzing to obtain valdecoxib; and reacting valdecoxib with propionic anhydride to obtain parecoxib. Compared with the prior art, the preparation method disclosed in the invention has the advantages of low initial raw material cost, simple and feasible technological process, low equipment requirement, and suitableness for the industrialized large-scale production.

The invention discloses a preparation method of a cyclooxygenase-2 inhibitor parecoxib. The method comprises the following steps that 1, benzaldoxime reacts with 1-phenylpropyne in the presence of tris(2-phenylpyridine)iridium (III), triethylamine and magnesium oxide under the illumination condition to obtain 5-methyl-3,4-diphenylisoxazole; 2, a stirring reaction is conducted on 5-methyl-3,4-diphenylisoxazole obtained in the first step and chlorosulfonic acid, dichloromethane extraction is conducted after the reaction is completed, a dichloromethane phase is directly added into ammonium hydroxide, an organic phase is separated, water washing, concentrating and ethanol recrystallization are conducted, and valdecoxib is obtained; 3, valdecoxib obtained in the second step reacts with propionic anhydride in the presence of triethylamine, and parecoxib is obtained. The preparation method of parecoxib is simple in step, high in yield and simple in posttreatment.

The invention discloses a method for synthesizing parecoxib. Widely sourced adenosine is taken as an initial raw material and is subjected to cyclization, amination and amidation sequentially. Fewer steps are adopted, few by-products are obtained, the yield is increased, and the production cost is reduced.

The invention discloses a method for preparing Parecoxib. The method for preparing the Parecoxib comprises the following steps of: performing sulfonation reaction on 1,2-diphenyl butanone serving as a raw material to obtain 1-phenyl-2-(4-sulfo phenyl)butanone; in the presence of alkali, performing condensation on the 1-phenyl-2-(4-sulfo phenyl)butanone and acetylchloride to prepare 1-phenyl-2-(4-sulfo phenyl)-2-acetyl butanone; performing cyclization on the 1-phenyl-2-(4-sulfo phenyl)-2-acetyl butanone and hydroxylamine hydrochloride to obtain 4-(5-methyl-3-phenyl-4-isoxazole)benzenesulfonic acid; performing chlorination and ammonolysis reaction to prepare Bextra; and reacting the Bextra with propionic anhydride to synthesize the Parecoxib. In the method, the raw materials are readily available and reaction conditions are not rigorous. The method is easy and convenient to operate and has certain industrialized value.

The invention discloses a method for preparing parecoxib freeze-dried powder injection. The problem in the prior art that in the cleaning and drying process, manual operation or increase of the dryingcost is needed is solved. The method for preparing parecoxib freeze-dried powder injection comprises the steps that firstly, phials are placed in a cleaning pool and cleaned; secondly, the phials cleaned are conveyed to a drying chamber through a conveying belt so that drying can be conducted and conveyed to a filling line after drying and cooling are conducted, the phials are filled with parecoxib freeze-dried powder through the filling line and covered with rubber plugs, and then the rubber plugs are sealed with aluminum foil covers; and thirdly, detection is conducted, wherein the phials are conveyed to a powder injection bottle labelling machine after being detected qualified and labelled, and the cleaning process in the first step is optimized. According to the method for preparing parecoxib freeze-dried powder injection, through optimization of the cleaning process, changes of different conveying directions can be achieved; in addition, steering of the phials can also be effectively achieved in the conveying process; and energy consumption of drying is saved.

The invention relates to double-layer microspheres loaded with parecoxib, interleukin-4 and bovine serum albumin and used for treating osteoarthritis and a preparation method of the double-layer microspheres, and belongs to the technical field of drug carrier research. Drugs carrying different physical and chemical properties are prepared by two-time multiple emulsion solvent volatilization method, the purpose of the invention is to solve the bottleneck problems of clinically restricting osteoarthritis drug treatment at present or meet urgent requirements of people for handling of pain and mobility inconvenience problems caused by inflammatory reaction during osteoarthritis attack, infection problem caused by repeated injection in articular cavity injection, and the problem of poor patient medication dependency caused by cardiotoxicity and gastrointestinal reaction caused by oral administration of non-steroidal anti-inflammatory drugs, and long-term chronic properties of osteoarthritis.

The invention discloses a hyaluronic acid-parecoxib PLGA microsphere as well as a preparation method and application thereof. Hydrophilic hyaluronic acid is modified, transparency is grafted with stearic acid so as to form amphiphilic macromolecules as a surfactant, so that the water-oil interfacial tension is reduced, and better adsorption of medicines is facilitated. A re-emulsifying solvent evaporation method is adopted. The preparation method comprises the following steps: dissolving PLGA into a proper amount of organic solvent, adding a small amount of a water-phase solution containing water-soluble medicines in a proportion, adding modified hyaluronic acid, carrying out ultrasonic treatment or oscillation treatment to obtain a W / O emulsion with a stable state, adding a large amount of an aqueous phase solution, carrying out secondary emulsification treatment to obtain a W / O / W emulsion, carrying out stirring evaporation to remove an organic solvent, and carrying out freeze dryingto obtain microsphere powder. By injecting the sustained-release microsphere, the acting time of the medicine can be effectively prolonged, the toxicity of the medicines is reduced, the irritation isreduced, and the medicines can be slowly released within several weeks.

The present invention relates to a process for preparing diaryl-substituted isoxazole using compounds of Formula (V) and Formula (VII): where Y is and to processes for preparing valdecoxib and parecoxib.

The invention discloses a preparation method of parecoxib for treating postoperative pain. The method comprises the following steps: 1) conducting a contact reaction between 3-(4-sulfonylphenyl)-4-phenyl-4-(1-pyrrolidyl)-3-butene-2-one and ammonium acetate in acetic acid at 90-100 DEG C; after the reaction, diluting with dichloromethane; regulating the pH to 6-7 with saturated sodium bicarbonate; concentrating the organic phase and washing; recrystallizing with ethanol; and drying to obtain 5-methyl-3-phenyl-4-(4-sulfonylphenyl)isoxazole; 2) enabling the product obtained in the step 1) to react with ammonium chloride at 35-45 DEG C in the presence of anion exchange resin to obtain 5-methyl-3-phenyl-4-(4-sulphonylaminophenyl)isoxazole; and 3) and 3) enabling the product obtained in the step 2) to react with propionic anhydride in the presence of triethylamine to obtain parecoxib. The parecoxib preparation method disclosed by the invention has the advantages of simple steps, mild conditions and high yield.

The invention discloses a method for preparing a cyclooxygenase-2 inhibitor parecoxib. The method comprises the following steps: 1) enabling benzaldoxime and 1-(4-sulfonyl phenyl)propyne to react in an illumination condition in the presence of tri(2-phenylpyridine)iridium (III), triethylamine and magnesium oxide to obtain 5-methyl-3-phenyl-4-(4-sulfonyl phenyl)isoxazole; 2) conducting a contact reaction between 5-methyl-3-phenyl-4-(4-sulfonyl phenyl)isoxazole obtained in the step 1) and thionyl chloride; after the reaction, extracting dichloromethane; directly adding the dichloromethane phase into ammonia water; separating organic phase; washing and concentrating; and recrystallizing with ethanol to obtain valdecoxib; and 3) enabling the valdecoxib obtained in the step 2) to react with propionic anhydride in the presence of triethylamine to obtain parecoxib. The parecoxib preparation method disclosed by the invention has the advantages of simple steps, high yield and simple aftertreatment.

The invention relates to the technical field of chemical synthesis of medicines, and concretely relates to a preparation method of a parecoxib meta-isomer impurity. The method comprises the followingsteps: 5-methyl-3-phenylisoxazole-4-carboxylic acid and 3-bromobenzenesulfonamide which are used as raw materials undergo a coupling reaction under the action of silver carbonate and a Pd catalyst togenerate N-[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonamide, and then the N-[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonamide and propionyl chloride undergo an acylation reaction to generateN-[[3-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]propanamide. Compared with the prior art, the preparation method of the invention has the advantages of cheap and easily available raw materials,simple synthesis steps, mild reaction conditions, easiness in control, reduction of the generation of byproducts, great improvement of the product yield, reduction of the cost, stable technological process, good reproducibility, and suitableness for large-scale production.

The invention discloses a method for preparing parecoxib for treating postoperative pain. The method comprises the following steps: 1) conducting a contact reaction between 3,4-diphenyl-4-(1-pyrrolidyl)-3-butene-2-one and ammonium acetate in acetic acid; after the reaction, diluting dichloromethane; regulating the pH value to 6-7 with saturated sodium bicarbonate; concentrating the organic phase and washing; recrystallizing with ethanol; and drying to obtain 5-methyl-3,4-diphenyl isoxazole; 2) stirring the obtained 5-methyl-3,4-diphenyl isoxazole and chlorosulfonic acid for reacting; adding anion exchange resin, and dropwise adding saturated ammonium chloride and dichloromethane for extraction; washing and concentrating; and recrystallizing with ethanol to obtain valdecoxib; and 3) enabling the valdecoxib obtained in the step 2) to react with propionic anhydride in the presence of triethylamine to obtain parecoxib. The method for preparing parecoxib, disclosed by the invention, has the advantages of simple steps, mild conditions and high yield.

The invention discloses a hyaluronic acid-parecoxib PLGA microsphere and its preparation method and application. The invention modifies the hydrophilic hyaluronic acid, and grafts the hyaluronic acid with stearic acid to obtain the hyaluronic acid. It is transformed into an amphiphilic polymer as a surfactant, thereby reducing the interfacial tension of water and oil, which is conducive to better adsorption of drugs. Using double emulsification solvent volatilization method, dissolve PLGA in an appropriate amount of organic solvent, add a small amount of aqueous phase solution containing water-soluble drugs in proportion, add modified hyaluronic acid, and process it by ultrasonic or vibration to obtain a stable state. W / O emulsion, then add a large amount of water phase solution for the second emulsification treatment to obtain W / O / W emulsion, then remove the organic solvent by stirring and evaporating, and freeze-dry to obtain microsphere powder. The injection of the sustained-release microspheres of the present invention can effectively prolong the action time of the drug, reduce the toxicity and irritation of the drug, and release the drug slowly within a few weeks.

The invention discloses a method for preparing a parecoxib intermediate. The method includes subjecting 1, 2-diphenyl-2-acetyl ethyl ketone and ammonium acetate to contact reaction with the presence of iodobenzene diacetate and potassium iodide, performing organic-phase concentration and washing after reaction, performing ethyl alcohol recrystallization, and drying to obtain 5-methyl-3, 4-diphenyl isoxazole. The method for preparing the parecoxib intermediate has the advantages of simplicity in procedure and high yield.

The invention discloses a treatment method and system for recycling tetrahydrofuran in a solution discharged in a parecoxib normal-phase workshop section. The treatment system comprises a waste liquid storage tank, a lifting pump, a membrane separation device, a condensation recycling device, a tetrahydrofuran collection tank and a vacuum pump device. The waste liquid storage tank is connected with the lifting pump, the lifting pump is connected with a liquid inlet of the membrane separation device through a pipeline, a liquid outlet of the membrane separation device is connected with the waste liquid storage tank, a gas outlet of the membrane separation device is connected with the condensation recycling device, a liquid outlet of the condensation recycling device is connected with the tetrahydrofuran collection tank, a gas outlet of the condensation recycling device is connected with the vacuum pump device, and the vacuum pump device is connected with the membrane separation device. Compared with the traditional art, the treatment way of recycling tetrahydrofuran in the solution discharged in the parecoxib normal-phase workshop section is charged, secondary pollution is avoided, no distillation still residual liquid is produced, the purity of separated-out tetrahydrofuran is high, the tetrahydrofuran is directly reused in a front end production process, the whole process is carried out at the temperature smaller than 70 DEG C, a product in the solution will not be damaged, and the running cost is low.

The invention discloses a preparation method of parecoxib for treating postoperative pain. The method comprises the following steps: 1) conducting a contact reaction between 3-(4-sulfonylphenyl)-4-phenyl-4-(1-pyrrolidyl)-3-butene-2-one and ammonium acetate in acetic acid at 90-100 DEG C; after the reaction, diluting with dichloromethane; regulating the pH to 6-7 with saturated sodium bicarbonate; concentrating the organic phase and washing; recrystallizing with ethanol; and drying to obtain 5-methyl-3-phenyl-4-(4-sulfonylphenyl)isoxazole; 2) enabling the product obtained in the step 1) to react with ammonium chloride at 35-45 DEG C in the presence of anion exchange resin to obtain 5-methyl-3-phenyl-4-(4-sulphonylaminophenyl)isoxazole; and 3) and 3) enabling the product obtained in the step 2) to react with propionic anhydride in the presence of triethylamine to obtain parecoxib. The parecoxib preparation method disclosed by the invention has the advantages of simple steps, mild conditions and high yield.

The present invention relates to a parecoxib derivative represented by a formula I, a racemate, a stereoisomer, a tautomer, an isotope marker, a solvate, a polymorphic substance, an ester or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the parecoxib derivative, a preparation method thereof, and pharmaceutical and veterinary pharmaceutical uses of the parecoxib derivative, and the formula I is disclosed in the invention.

The invention discloses a method for preparing parecoxib. The method comprises the following steps: an initial raw material 3-oxo-2-phenylbutanoyl chloride and benzene undergo a Friedel-Crafts reaction to generate 1,2-diphenylbutane-1,3-dione, 1,2-diphenylbutane-1,3-dione is sulfonated by chlorosulfonic acid or concentrated sulfuric acid / acetyl chloride to obtain 4-(1,3-dioxo-1-phenylbutyl-2-yl)-1-sulfonyl chloride, 4-(1,3-dioxo-1-phenylbutyl-2-yl)-1-sulfonyl chloride is acted by ammonia water to generate 4-(1,3-dioxo-1-phenylbutyl-2-yl)-1-sulfonamide, and 4-(1,3-dioxo-1-phenylbutyl-2-yl)-1-sulfonamide reacts with propionic anhydride or propionyl chloride to obtain N-(4-(1,3-dioxo-1-phenylbutyl-2-yl)phenylsulfonyl)propionamide, N-(4-(1,3-dioxo-1-phenylbutyl-2-yl)phenylsulfonyl)propionamide undergoes condensation by using hydroxylamine hydrochloride to synthesize a ring, and dehydration is carried out under an acidic condition to obtain parecoxib. The parecoxib is prepared from 3-oxo-2-phenylbutanoyl chloride as the initial raw material through the Friedel-Crafts reaction, a sulfonation reaction, an amidation reaction and a condensation reaction. The method has the advantages of low cost of the initial raw material, simple process, low requirements of reaction conditions, simple post-treatment operation, high product yield and purity, and realization of large-scale production.

The invention relates to a method for preparing Parecoxib, and belongs to the synthesis field of pharmaceutical chemistry. 1,2-diphenyl-ethanone is used as an starting raw material, a reaction is carried out between the starting raw material and chlorosulfonic acid / ammonia-water, in order to prepare 4-(2-oxo-2-phenethyl)benzenesulfonamide, and an acylation reaction is carried out for 4-(2-oxo-2-phenethyl)benzenesulfonamide, and finally hydroxylamine hydrochloride is used for preparing Parecoxib by condensation and cyclization. Compared with the prior art, the method has the advantages of mild reaction conditions, short synthetic route, simple operation, and low cost.

The invention discloses a preparation method of a cyclooxygenase-2 inhibitor parecoxib. The method comprises the following steps that 1, benzaldoxime reacts with 1-phenylpropyne in the presence of tris(2-phenylpyridine)iridium (III), triethylamine and magnesium oxide under the illumination condition to obtain 5-methyl-3,4-diphenylisoxazole; 2, a stirring reaction is conducted on 5-methyl-3,4-diphenylisoxazole obtained in the first step and chlorosulfonic acid, dichloromethane extraction is conducted after the reaction is completed, a dichloromethane phase is directly added into ammonium hydroxide, an organic phase is separated, water washing, concentrating and ethanol recrystallization are conducted, and valdecoxib is obtained; 3, valdecoxib obtained in the second step reacts with propionic anhydride in the presence of triethylamine, and parecoxib is obtained. The preparation method of parecoxib is simple in step, high in yield and simple in posttreatment.

The invention relates to a parecoxib derivative as shown in a formula I, a racemate, a stereoisomer, a tautomer, an isotope label, a solvate, a polymorphic substance, ester or pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the parecoxib derivative, a preparation method of the parecoxib derivative, and application of the parecoxib derivative to medicines and veterinary medicines. The structure of Formula I is as follows.

The invention discloses a preparation method of a cyclooxygenase-2 inhibitor parecoxib intermediate. The preparation method comprises the following steps: in the presence of iodobenzene diacetate and potassium iodide, carrying out contact reaction on 1-phenyl-2-(4-sulfophenyl)-2-acetylethylketone and ammonium acetate; and after the reaction finishes, concentrating the organic phase, washing with water, recrystallizing with ethanol, and drying to obtain the 5-methyl-3-phenyl-4-(4-sulfophenyl)isoxazole. The method for preparing the parecoxib intermediate has the advantages of simple steps, mild conditions and high yield.

The invention provides a preparation and refining method of parecoxib and an intermediate thereof, wherein the parecoxib can be prepared with high efficiency, high yield and high purity through sulfonation, amination and acylation steps, and the method is more suitable for industrial large-scale production.

The invention discloses a method for preparing parecoxib. The method comprises the following steps: an initial raw material 3-oxo-2-phenylbutanoyl chloride and benzene undergo a Friedel-Crafts reaction to generate 1,2-diphenylbutane-1,3-dione, 1,2-diphenylbutane-1,3-dione is sulfonated by chlorosulfonic acid or concentrated sulfuric acid / acetyl chloride to obtain 4-(1,3-dioxo-1-phenylbutyl-2-yl)-1-sulfonyl chloride, 4-(1,3-dioxo-1-phenylbutyl-2-yl)-1-sulfonyl chloride is acted by ammonia water to generate 4-(1,3-dioxo-1-phenylbutyl-2-yl)-1-sulfonamide, and 4-(1,3-dioxo-1-phenylbutyl-2-yl)-1-sulfonamide reacts with propionic anhydride or propionyl chloride to obtain N-(4-(1,3-dioxo-1-phenylbutyl-2-yl)phenylsulfonyl)propionamide, N-(4-(1,3-dioxo-1-phenylbutyl-2-yl)phenylsulfonyl)propionamide undergoes condensation by using hydroxylamine hydrochloride to synthesize a ring, and dehydration is carried out under an acidic condition to obtain parecoxib. The parecoxib is prepared from 3-oxo-2-phenylbutanoyl chloride as the initial raw material through the Friedel-Crafts reaction, a sulfonation reaction, an amidation reaction and a condensation reaction. The method has the advantages of low cost of the initial raw material, simple process, low requirements of reaction conditions, simple post-treatment operation, high product yield and purity, and realization of large-scale production.

The invention discloses a system for preparing a parecoxib freeze-dried powder injection. The problem in the prior art that in the process of cleaning and drying, manual operation is needed, or the drying cost needs to be increased is solved. The system comprises a cleaning pool, a drying chamber, a filling line and a covering device; a conveying line is further arranged in the cleaning pool and comprises a conveying belt, a driving device which drives the conveying belt to rotate and a limiting strip which is arranged above the conveying belt and forms a bottleneck passage for penicillin bottles between the limiting strip and the conveying belt; the conveying belt comprises a conveying track which is opened in the top and provided with an inner cavity, a flexible connecting strip which isarranged along the conveying track, a pulley set which is installed on the flexible connecting strip and located in the inner cavity and a push rod, wherein one end of the push rod is fixed to the pulley set, and the other end of the push rod extends out of the conveying track through the top opening. According to the system, change of different conveying directions can be achieved through a monotonous structure, veering of the penicillin bottles in the conveying process can be effectively achieved, and the energy consumption for drying is reduced.

The invention relates to a method for preparing Parecoxib, and belongs to the synthesis field of pharmaceutical chemistry. 1,2-diphenyl-ethanone is used as an starting raw material, a reaction is carried out between the starting raw material and chlorosulfonic acid / ammonia-water, in order to prepare 4-(2-oxo-2-phenethyl)benzenesulfonamide, and an acylation reaction is carried out for 4-(2-oxo-2-phenethyl)benzenesulfonamide, and finally hydroxylamine hydrochloride is used for preparing Parecoxib by condensation and cyclization. Compared with the prior art, the method has the advantages of mild reaction conditions, short synthetic route, simple operation, and low cost.