- Preparation method of atazanavir intermediate
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The invention relates to a preparation method of an atazanavir intermediate, and belongs to the technical field of drug intermediate synthesis. In order to solve the problems of unstable reaction and difficult control in the prior art, the invention provides a preparation method of an atazanavir intermediate, which is characterized by comprising the following steps of: under the catalysis of a catalytic amount of Lewis acid I, carrying out a ring-opening addition reaction on tert-butyl hydrazinocarboxylate and (2R, 3S)-1, 2-epoxy-3-tert-butyloxycarborylamino-4-phenylbutane in a water-insoluble organic solvent at the temperature of 20-40 DEG C to obtain corresponding reaction liquid; and then adding Lewis acid II into the reaction liquid to carry out deprotection treatment so as to remove the N-Boc group, thereby obtaining a corresponding product, namely a compound as shown in a formula V. According to the invention, one-step synthesis can be realized, tedious intermediate treatment processes are reduced, the technological process is simple, side reactions are effectively reduced, and the effects of high conversion rate and high purity are realized.
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Paragraph 0022; 0026-0037
(2021/11/06)
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- A process for preparing Atazanavir monomer
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The invention discloses a method for preparing an atazanavir monomer. The method is applied to the technical field of medicines and comprises steps as follows: at the proper temperature, weak base is used as an acid-binding agent, under a certain organic solvent condition, N-methoxycarbonyl-L-tert-leucine firstly reacts with thionyl chloride to produce N-methoxycarbonyl-L-tert-leucine acyl chloride, then the N-methoxycarbonyl-L-tert-leucine acyl chloride and 1-[4-(pyridin-2-yl)-phenyl]-4(S)-hydroxyl-5(S)-2,5-diamino-6-phenyl-2-azahexane have an amide formation reaction at the room temperature, and the atazanavir monomer is obtained. The method has the advantages as follows: (1), the thionyl chloride is cheap, so that the costs of raw materials are effectively reduced, and the method is suitable for industrialization; (2), the produced pollution is less and is converted into soluble effluent brine after after-treatment, so that the method is relatively environment-friendly; (3), the operation is simple, the product yield is high, separation and purification are easy, and the method is suitable for industrial production.
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Paragraph 0018-0019
(2017/08/25)
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- PROCESS FOR PREPARING ATAZANAVIR SULPHATE
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The present invention relates to a process for the preparation of Compound (A): (Formula (A)) wherein the process comprises contacting atazanavir base (Compound (II)) with sulphuric acid in a combination of two or more solvents and isolating compound (A).
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Page/Page column 19
(2014/09/03)
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- Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2′ ligands in pseudosymmetric dipeptide isosteres
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A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2′ ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure-activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.
- Reddy, G. S. Kiran Kumar,Ali, Akbar,Nalam, Madhavi N. L.,Anjum, Saima Ghafoor,Cao, Hong,Nathans, Robin S.,Schiffer, Celia A.,Rana, Tariq M.
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p. 4316 - 4328
(2008/02/12)
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- HIV PROTEASE INHIBITING COMPOUNDS
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A compound of the formula (I) is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
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Page/Page column 146
(2010/02/12)
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- HIV PROTEASE INHIBITING COMPOUNDS
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A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
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Page/Page column 94
(2010/02/12)
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