33 results about "Darunavir" patented technology

The invention discloses synthetic methods of hexahydrofuro[2,3-b]furan-3-ol and an enantiomer thereof. The synthetic method of hexahydrofuro[2,3-b]furan-3-ol comprises the step c or the step b to the step c or the step a to the step c in the following synthetic route as shown in the description. The synthetic method of the enantiomer (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-ol comprises the step c to the step f or the step b to the step f or the step a to the step f in the following synthetic route as shown in the description, wherein R1 is selected from C1 to C4 alkyl or aralkyl, and R2 is selected from C1 to C4 alkyl. The synthetic methods provided by the invention have the advantages of cheap and easily available raw materials, simple operation, low cost and the like, are suitable for large-scale production, and have practical value for realization of industrialized production of darunavir.

The invention relates to a preparation method of a Darunavir amorphous matter. Specifically, the method disclosed by the invention comprises the steps of: mixing a Darunavir-containing first solution with a second solvent so as to obtain precipitated amorphous Darunavir. The product made by the method has high purity and good stability. The method has the advantages of simple operation, low production cost, environmental friendliness, and suitability for industrialized production.

A process for the preparation of Darunavir comprises the reacting of 4-amino-N-(2R,3S) (3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-benzenesulfonamide with (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol derivative in N-methyl-2-pyrrolidinone and isolating the resulting Darunavir. The process yields Darunavir with a very low level of the difuranyl impurity.

The present invention relates to the technical field of pharmaceutical chemistry, particularly to a darunavir amorphous form preparation method. According to the present invention, the preparation method belongs to the anti-solvent method in crystal form preparation screening, wherein the crystal form is screened by using the anti-solvent in the prior art while the final product is the specific crystal form of darunavir such as WO2013114382 and is not the amorphous form; and the preparation method of the present invention is different from the method in the prior art, has the high production capacity, and is suitable for industrial production. The amorphous form of darunavir is defined in the specification.

The invention discloses a medical intermediate. The medical intermediate has the chemical structure shown as a formula II shown in the description, wherein the R is selected from methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl, tertiary butyl, sec-butyl, phenyl and naphthyl. The invention also discloses a preparation method of the intermediate; the operation is simple; the cost is low; the preparation method is suitable for scale production. The intermediate can be used for preparing a key intermediate of darunavir; important significance and practical values are realized on the industrial production of the darunavir.

The present invention relates to a process for the preparation of darunavir, a nonpeptide protease inhibitor (PI), useful for the treatment of HIV / AIDS patients harboring multidrug-resistant HIV-1 variants that do not respond to previously existing HAART regimens. The present invention further relates to processes for the stereo-directed preparation of darunavir intermediates, in particular (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol and to certain novel intermediates obtained by such processes.

The invention belongs to the field of chemical synthesis, and discloses a method for preparing a darunavir intermediate namely (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol. According to the method, (R)-3-hydroxyl-4-acetaldol derivatives (I) are used as raw materials, and under the action of a catalyst, the (R)-3-hydroxyl-4-acetaldol derivatives (I) stereoselectively react with an ethanediol derivative so as to obtain an intermediate (II); and the obtained intermediate (II) is subjected to protecting group removal, and under the acid condition, cyclization is performed, so that the (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol is obtained. According to the preparation method, the raw materials are low in cost and easy to obtain, the reaction stereoselectivity is high, the operation is simple, the route is short, the cost is low, and the method is suitable for industrialized production of darunavir.(As shown in the description).

A process for the preparation of Darunavir comprises the reacting of 4-amino-N-(2R, 3S) (3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-benzenesulfonamide with (3R, 3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol derivative in N-methyl-2-pyrrolidinone and isolating the resulting Darunavir. The process yields Darunavir with a very low level of the difuranyl impurity.

The invention relates to the technical field of medicines and discloses a method for preparing darunavir. The method comprises the following step: preparing 20-30 parts of cobalt, 10-20 parts of triethylamine, 10-20 parts of ferrous oxide, 10-20 parts of zinc oxide, 3-5 parts of 1.2 equivalent of marina hydrogen methane, 20-30 parts of zinc, 50-80 parts of a ferric nitrite solution, 30-40 parts ofa metal base, 40-50 parts of alumina, 10-20 parts of silica, 3-5 parts of p-acetamide benzoyl sulfonyl chloride, 3-5 parts of a precipitant, 50-80 parts of an ethanol solution and 20-30 parts of nickel for later use. According the method for preparing the darunavir, 20-30 parts of cobalt, 10-20 parts of triethylamine, 10-20 parts of ferrous oxide, 10-20 parts of zinc oxide, 3-5 parts of 1.2 equivalent of marina hydrogen methane, 10-20 parts of silica, 3-5 parts of p-acetamide benzoyl sulfonyl chloride, 3-5 parts of the precipitant, 50-80 parts of the ethanol solution and 20-30 parts of nickelare adopted for later use, the reaction materials used in the method are low in price and low in reaction environment requirement, correspondingly, the preparation cost of the darunavir is greatly reduced, patients can afford the darunavir, and the darunavir can truly benefit the patients.

The present invention relates to pharmaceutical antiretroviral compositions comprising a combination of antiretroviral agents (darunavir, dolutegravir and ritonavir), the manufacturing process thereof and use of the said compositions for the prevention, treatment or prophylaxis of HIV infection.

The invention relates to a composition with an improved dissolution rate. The composition comprises a salt formed by darunavir and an acidic polymer. The darunavir: acidic polymer salt composition hasa faster dissolution rate and better stability. The composition can be applied to the treatment of viral infection diseases, such as acquired immunodeficiency syndrome (HIV), viral hepatitis and coronavirus infection.

The present invention relates to an industrially feasible and economically viable process for the preparation of (1S,2R)-3-[[4-aminophenyl)-sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenyl-methyl)propyl]amine of formula I and its salt thereof and optionally converting it to HIV-protease inhibitors like Darunavir, Amprenavir or its prodrug Fosamprenavir.

The invention discloses a method for preparing a darunavir intermediate, in particular to a method for preparing a compound of formula I.

The embodiment of the invention discloses a method for preparing a darunavir intermediate through biological catalysis, and belongs to the technical field of a biological catalysis method and an application. 3S-1-chloro-3-tert-butyloxycarbonylamino-4-phenyl-2-butanol can be converted into (2S, 3S)-1-chloro-3-tert-butyloxycarbonylamino-4-phenyl-2-butanol through a ketoreductase mutant; the ketoreductase mutant is derived from wild type ketoreductase of Starmella magnoliae, has higher alcohol dehydrogenase activity compared with a wild type sequence, has 90% or above similarity with SEQ ID NO.8and has one or more of the following characteristics: I54E, S85A and K182V; and the sequence of the ketoreductase mutant is shown as SEQ ID NO. 4. Alcohols are used for coenzyme circulation, the substrate concentration is up to 110 g / L, the ratio of the substrate dosage to the NADP dosage is up to 1100: 1, the number of times of coenzyme circulation is high, and the downstream application range iseffectively widened.

Provided are a process for preparation of darunavir or solvates or a pharmaceutically acceptable salt thereof substantially free of bisfuranyl impurities and a process for preparation of amorphous darunavir using the darunavir propionate solvate.

This invention relate to solid oral dosage forms of tire HIV inhibitor Darunavir and / or a pharmaceutically acceptable salt or solvate thereof, and combination formulation thereof.

The invention discloses a method for synthesizing a darunavir intermediate by using a microchannel reactor. The synthesis method comprises the following steps: taking 1-benzyl-2, 3 epoxy n-propyl-tert-butyl carbamate as an initial raw material, and carrying out amination, sulfonylation, Boc protecting group removal and microchannel hydrogenation reduction reaction to generate the darunavir intermediate 4-amino-N-(2R, 3S)-(3-amino-2-hydroxy-4-phenyl-butyl)-N-isobutyl-benzenesulfonamide. The method has the advantages of simplicity in operation, safety, environment friendliness, easiness in batch synthesis, low energy consumption and high purity.

The present invention belongs to the technical field of medicines and discloses a darunavir inhaled dry powder pharmaceutical composition, and a preparation method and medical uses of the composition.

The present invention provides a process for the preparation of darunavir or solvates or a pharmaceutically acceptable salt thereof substantially free of bisfuranyl impurities, particularly darunavir propionate solvate. The present invention also provides a process for preparation amorphous darunavir using the darunavir propionate solvate.

The invention discloses application of darunavir in preparation of the medicine for treating the pulmonary fibrosis diseases, darunavir has a good effect on pulmonary fibrosis, has no adverse reaction, can slow down bleomycin-induced pulmonary fibrosis of mice, provides a new medicine for treating, relieving or improving the pulmonary fibrosis diseases, and has a good application prospect.

The present invention relates to a novel tenofovir disoproxil salt and the preparation method thereof. The crystalline form of tenofovir disoproxil orotate according to the present invention is an anhydride and it has superior physicochemical properties that are useful in pharmaceutical preparation as it resolves problems caused by physicochemical properties of tenofovir disoproxil fumarate. Namely, the crystalline form of tenofovir disoproxil orotate according to the present invention has a better than equal light stability compared to tenofovir disoproxil fumarate and has a superior stability especially under extreme stress conditions. Additionally, it is neither corrosive nor harmful to human body, thus making it safe for preparation and easy to manage. All of these characteristics make this invention useful for mass production. The present invention also provides a preparation method with and without using organic solvent, thus providing an industrially applicable and environment-friendly preparation method. Furthermore, tenofovir disoproxil orotate prepared according to the present invention can be used as an antiviral treating agent and can also be made into an anti-HIV treating composition if mixed with other drugs that have anti-HIV activity. The composition can be made into mixtures with one to six of the following other anti-HIV active ingredient medications that include Emtricitabine, Efavirenz, Rilpivirenz, Cobicistat, Elvitegravir, Raltegravir, Ritonavir, Lopinavir, Darunavir, Atazanavir and salts thereof for the treatment of HIV infection.

The invention relates to the technical field of chemical engineering and discloses a preparation method of darunavir, which includes a step of preparing raw materials comprising: 20-30 mg of N-dibenzyl-L-methyl phenylalanine ester, 40-90 mg of a N-hydroxyl compound, 20-40 mg of Binqing methane in 1 equivalent, 100-150 mg of butyl lithium, 50-80 mg of a tetrahydrofuran solvent, 70-110 mg of amines,60-100 mg of (2S,3R)-2-amino-4-chloro-phenylbutane-3-ol, 40-60 mg of a halogenated aromatic ring compound, 10-20 mg of triethylamine and dichloromethane, 5-20 mg of di-tert butyl dicarbonate in 1.3 equivalents, and 20-40 mg of metal alkali; and preserving 20-30 mg of the N-dibenzyl-L-methyl phenylalanine ester, 20-40 mg of the Binqing methane in 1 equivalent, 100-150 mg of the butyl lithium and 70-110 mg of the amines at -20 DEG C for later use. The preparation method is low in demand on environment, avoids complex operations in conventional preparation methods, is easier to prepare the darunavir and is not liable to cause waste on consumables, so that the method is convenient to carry out.

The invention relates to the field of biochemical technology, in particular to an industrial production method of a darunavir intermediate (3R, 3aS, 6aR)-hydroxyhexahydrofuro[2,3-β]furylsuccinimidyl carbonate. Compared with the existing technology, the industrial production method of (3R, 3AS, 6AR)-hydroxyhexahydrofuro[2,3-β]furylsuccinimide-based carbonate provided by the present invention can efficiently and stably produce High-quality (3R,3AS,6AR)-hydroxyhexahydrofuro[2,3-β]furylsuccinimide carbonate was produced with a purity greater than 99% and an unknown single impurity less than 0.1%.

The invention relates to the field of medicine synthesis, particularly to a preparation method for reducing a lactone structure into hemiacetal, particularly to a preparation method for a darunavir intermediate. According to the method, a compound shown in a formula I is reduced under the conditions of alkali, aluminum trichloride, a reducing agent and a solvent to prepare a compound shown in a formula II, or the compound shown in the formula I is reduced under the conditions of alcohol, alkali, aluminum trichloride, a reducing agent and a solvent to prepare the compound shown in the formula II, wherein R1, R2, R3, R4, R5 and R7 are hydrogen, hydroxyl, amino, alkyl, aryl, fluorine, chlorine or bromine, R6 and R8 are hydrogen, hydroxyl, amino, benzoyloxy, alkyl, aryl, fluorine, chlorine orbromine, and n is 0 or 1.