55 results about "Atazanavir" patented technology

A method for improving the pharmacokinetics of an orally administered drug that is directly metabolized by UGT1A1 comprises orally administering to a mammal in need of treatment with the drug a combination of the drug or a pharmaceutically acceptable salt thereof and atazanavir or a pharmaceutically acceptable salt thereof.

A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated sulfuric acid in an amount to react with less than about 15% by weight of the free base, seeds of Form A crystals of atazanavir bisulfate are added to the reaction mixture, and as crystals of the bisulfate form, additional concentrated sulfuric acid is added in multiple stages at increasing rates according to a cubic equation, to effect formation of Form A crystals of atazanavir bisulfate. A process is also provided for preparing atazanavir bisulfate as Pattern C material. A novel form of atazanavir bisulfate is also provided which is Form E3 which is a highly crystalline triethanolate solvate of the bisulfate salt from ethanol.

The invention relates to pharmaceutical compositions containing a combination of atazanavir and ritonavir, to methods of making them, and their use in medicine.

The invention discloses a method for preparing an A-type crystal of Atazanavir disulfate. The method comprises the following steps that a, Atazanavir free alkali is placed in ethyl alcohol, the mixture is stirred at room temperature, then concentrated sulfuric acid is added dropwise, the reaction liquid is heated and stirred, then an inert solvent is added, cooling and crystallization are carried out, drying is carried out after filtering, and an Atazanavir ethyl alcohol compound E-type crystal is obtained, wherein the molar concentration of concentrated sulfuric acid is preferably 15 mol / L to 18.4 mol / L; b, the Atazanavir ethyl alcohol compound E-type crystal obtained in the step a is placed in acetone, heating, refluxing and stirring are carried out, drying is carried out after cooling and filtering, and the A-type crystal of Atazanavir disulfate is obtained. According to the crystal transformation preparation method, the operability of the process is improved, the external properties of the product are improved, and the quality and purity of the product are improved.

Activated haptens useful for generating immunogens to the HIV protease inhibitor atazanavir, immunogens useful for producing antibodies to atazanavir, and antibodies and labeled conjugates useful in immunoassays for determination of atazanavir. The haptens feature an activated functionality at the central, non-terminal hydroxyl group.

The invention discloses an alcohol dehydrogenase for producing an Atazanavir intermediate and belongs to the technical field of medical biology. The alcohol dehydrogenase shows stronger catalytic activity than a wild alcohol dehydrogenase shown as SEQ ID NO.8 and can be obtained by means of in-vitro recombination, polynucleotide mutagenesis, DNA shuffling, error-prone PCR, directional evolution methods and the like. The alcohol dehydrogenase has one or more mutations of following characteristics including T37A, D38E, P41K, D44N, V45K. The alcohol dehydrogenase has the advantages that, the reaction conditions are mild, the requirement for equipment is low, high temperature or cooling in a production process is not required, and the energy consumption is low; since enzyme catalysis has highefficiency and exclusive selectivity, no by-products are generated when a method is utilized to produce key intermediates of Atazanavir, and purification is convenient. In addition, a reaction solventmainly consists of water, the discharge amount of three wastes is small, and the alcohol dehydrogenase is environmentally friendly.

The invention provides novel application of atazanavir medicines, and in particular relates to application of atazanavir in inhibiting generation and development of acute lung injury / acute respiratory distress syndrome (ALI / ARDS) and pulmonary fibrosis by inhibiting apoptosis of I type alveolar epithelial cells and promoting expression of receptor for advanced glycation endproducts (RAGE) of I type alveolar epithelial cells, so as to prevent or treat ALI / ARDS and pulmonary fibrosis. According to the application, the injected dose of atazanavir ranges from 100 to 2000mg, preferably 100 to 1000mg; the oral dose of atazanavir ranges from 200 to 6000mg, preferably 200 to 3000mg.

A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated sulfuric acid in an amount to react with less than about 15% by weight of the free base, seeds of Form A crystals of atazanavir bisulfate are added to the reaction mixture, and as crystals of the bisulfate form, additional concentrated sulfuric acid is added in multiple stages at increasing rates according to a cubic equation, to effect formation of Form A crystals of atazanavir bisulfate.A process is also provided for preparing atazanavir bisulfate as Pattern C material. A novel form of atazanavir bisulfate is also provided which is Form E3 which is a highly crystalline triethanolate solvate of the bisulfate salt from ethanol.

The invention relates to a new synthetic method of an HIV-1 protease inhibitor, Atazanavir, which adopts a convergent-typed synthetic strategy, introduces a construction unit, methoxycarbonyl-tert-lencyl, as an N atom protecting group in the whole early synthetic stage, and takes the diastereomeric selective reduction of aminoketone as the key and final reaction step of the new process. The method comprises the steps that: the compound of formula V, namely, N-1-[N-(methoxycarbonyl)-L-tert-leucine]-N-2-[4-(2-pyridyl)-phenmethyl]hydrazine, and the compound of formula VI, namely, (S)-1-((S)-4-chlorine-3-carbonyl-1-phenyl butane-2-yl-2-amino)-3, 3-dimethyl-1-carbonyl butane-2-yl-methyl carbamate, are treated with nucleophilic substitution reaction to generate the compound of formula VII, namely, 1-[4-(2-pyridyl)phenyl]-5(S)-2, 5-bis{[N-(methoxycarbonyl)-L-tert-leucineyl] amino}-4-carbonyl-6-phenyl-2-azahexane; and the compound of formula VII is treated with reduction reaction to generate the Atazanavir. The invention has the advantages of less process route steps, easily-controlled reaction conditions, simple and convenient operation, low-price and easily-obtained raw material, high product yield, low cost and being suitable for large-scale production.

The present invention relates to the field of chemical medicaments. Disclosed is an Atazanavir preparation method, with a reaction formula as represented in figure (I). The present invention uses DEPBT as a condensing agent; 1-[4-(pyridine-2-yl)-phenyl]-4(S)-hydroxy-5(S)-2, 5-diamino-6- phenyl-2-azahexane is reacted with N-methoxycarbonyl-L-tertiary leucine in an organic solvent to give the Atazanavir. The condensing agent normally used in the reaction in existing literatures is TPTU, a combination of carbon diimine compounds and benzotriazole compounds, or only the carbon diimine compounds. However, the compounds are expensive, toxic and heavily pollutive. The present invention uses inexpensive, safe and environment-friendly DEPBT as the condensing agent, and provides an economically feasible, safe and environment-friendly Atazanavir preparation method with high yield and easy product separation.

Formulations of the HIV compounds atazanavir and cobicistat, and methods of treatment utilizing these formulations, are set forth.