- Design and synthesis of selenazole-substituted ritonavir analogs
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With the help of Surflex-Dock calculation, two ritonavir analogs in which one thioazole unit was replaced by selenazole have been designed and synthesized. The key selenazole structure was constructed from β-azido diselenide through a cascade diselenide cleavage/selenocarbonylation/Staudinger reduction/aza-Wittig reaction and a following MnO2 oxidation. The accordingly prepared compounds exhibited good anti-HIV-1 (IIIB) activities comparable to that of the original ritonavir, as well as the positive SI values.
- Qiao, Junfei,Zhao, Chuanfang,Liu, Jun,Du, Yuguo
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- NOVEL PROCESS FOR THE PREPARATION OF 1,3-THIAZOL-5-YLMETHYL [(2R,5R)-5- CARBAMOYL) AMINO] -4-(MORPHOLIN-4-YL)BUTANOYL]AMINO}-1,6-DIPHENYLHEXAN-2-YL]CARBAMATE
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The present invention relates to novel processes for the preparation 1,3-Thiazol-5-ylmethyl[(2R,5R)-5-{[(2S)-2-[(methyl{[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl} carbamoyl)amino]-4-(morpholin-4-yl)butanoyl]amino}-1,6-diphenylhexan-2-yl] carbamate having the following structural formula-1 and it's intermediates thereof.
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Paragraph 0163
(2018/02/28)
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- INHIBITORS OF CYTOCHROME P450
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The present application provides for a compound of Formula I, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.
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Paragraph 0878
(2015/11/10)
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- METHODS AND INTERMEDIATES FOR PREPARING PHARMACEUTICAL AGENTS
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The invention provides methods and intermediates that are useful for preparing a compound of formula I: and salts thereof.
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Page/Page column 19
(2010/10/19)
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- MODULATORS OF PHARMACOKINETIC PROPERTIES OF THERAPEUTICS
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The present application provides for a compound of Formula I, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.
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Page/Page column 188-189
(2008/06/13)
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- Retroviral protease inhibiting compounds
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A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.
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- RETROVIRAL PROTEASE INHIBITING COMPOUNDS
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A compound of the formula: STR1 is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
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- Process for the preparation of disubstituted carbonates
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The present invention relates to a process for the preparation of cabonate compounds useful for the preparation of compounds which are human immunodeficiency virus (HIV) protease inhibitors. The compounds have formula I: STR1 wherein R9 is hydrogen or lower alkyl, and the thiazolyl ring can be unsubituted or substituted with a lower alkyl group.
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- Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy
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The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption. Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 μM) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.
- Kempf, Dale J.,Sham, Hing L.,Marsh, Kennan C.,Flentge, Charles A.,Betebenner, David,Green, Brian E.,McDonald, Edith,Vasavanonda, Sudthida,Saldivar, Ayda,Wideburg, Norman E.,Kati, Warren M.,Ruiz, Lisa,Zhao, Chen,Fino, Lynnmarie,Patterson, Jean,Molla, Akhteruzzaman,Plattner, Jacob J.,Norbeck, Daniel W.
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p. 602 - 617
(2007/10/03)
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- Pharmaceutical composition for inhibiting HIV protease
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A pharmaceutical composition is disclosed which comprises a solution of an HIV protease inhibiting compound in a pharmaceutically acceptable organic solvent comprising a mixture of (1) (a) a solvent selected from propylene glycol and polyethylene glycol or (b) a solvent selected from polyoxyethyleneglycerol triricinoleate, polyethylene glycol 40 hydrogenated castor oil, fractionated coconut oil, polyoxyethylene (20) sorbitan monooleate and 2-(2-ethoxyethoxy)ethanol or (c) a mixture thereof and (2) ethanol or propylene glycol.
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- Pharmaceutical composition
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A solid pharmaceutical composition is disclosed which comprises a pharmaceutically acceptable adsorbent or a mixture of pharmaceutically acceptable adsorbents to which is adsorbed a mixture of (1) a pharmaceutically acceptable organic solvent or a mixture of pharmaceutically acceptable organic solvents, (2) an HIV protease inhibiting compound and (3) one or more pharmaceutically acceptable acids. The solid composition can optionally be encapsulated in a hard gelatin capsule.
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- RETROVIRAL PROTEASE INHIBITING COMPOUNDS
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A retroviral protease inhibiting compound of the formula: STR1 is disclosed wherein R 1, R 2, R 5, R 6, Y m and Y' n are herein defined.
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