- The Chiron Approach to (3 R,3 aS,6 aR)-Hexahydrofuro[2,3- b]furan-3-ol, a Key Subunit of HIV-1 Protease Inhibitor Drug, Darunavir
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We describe an enantioselective synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol which is a key subunit of darunavir, a widely used HIV-1 protease inhibitor drug for the treatment of HIV/AIDS patients. The synthesis was achieved in optically pure form utilizing commercially available sugar derivatives as the starting material. The key steps involve a highly stereoselective substrate-controlled hydrogenation, a Lewis acid catalyzed anomeric reduction of a 1,2-O-isopropylidene-protected glycofuranoside, and a Baeyer-Villiger oxidation of a tetrahydrofuranyl-2-aldehyde derivative. This optically active ligand alcohol was converted to darunavir efficiently.
- Ghosh, Arun K.,Markad, Shivaji B.,Robinson, William L.
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p. 1216 - 1222
(2020/12/22)
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- Crystalline Darunavir
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The present invention relates to a non-solvated crystalline Darunavir, process for its preparation and pharmaceutical composition comprising it. The present invention also relates to a process for the preparation of amorphous Darunavir from a non-solvated crystalline Darunavir.
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Paragraph 0059
(2014/12/09)
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- CRYSTALLINE DARUNAVIR
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The present invention relates to a non-solvated crystalline Darunavir, process for its preparation and pharmaceutical composition comprising it. The present invention also relates to a process for the preparation of amorphous Darunavir from a non-solvated crystalline Darunavir.
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Page/Page column 10
(2013/08/15)
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- PROCESS FOR THE PREPARATION OF SULFONAMIDES USEFUL AS RETROVIRAL PROTEASE INHIBITORS
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The present invention relates to a process for the preparation of sulfonamides useful as retroviral protease inhibitors.
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Page/Page column 34
(2013/03/26)
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- Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance
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Summary The rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (PIs) using the substrate envelope model, which confines inhib
- Nalam, Madhavi N.L.,Ali, Akbar,Reddy, G.S. Kiran Kumar,Cao, Hong,Anjum, Saima G.,Altman, Michael D.,Yilmaz, Nese Kurt,Tidor, Bruce,Rana, Tariq M.,Schiffer, Celia A.
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p. 1116 - 1124
(2013/10/01)
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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 114
(2011/01/12)
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- Research and development of an efficient synthesis of hexahydrofuro[2,3-b] furan-3-ol moiety - a key component of the HIV protease inhibitor candidates
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A highly efficient method for synthesizing racemic hexahydrofuro[2,3-b] furan-3-ol has been developed utilizing a lanthanide catalyst, such as Yh(fod)3, to promote condensation of 23-dihydrofuran and glycolaldehyde dimer. Access to either optically enriched enantiomer of bisfuran alcohol can be obtained by using this method employing chiral ligands with the lanthanide catalyst In support of Gilead Sciences' protease inhibitor project, this method has been demonstrated to be a robust and scalable process with potential application for the construction of a variety of furo[2,3-b]furan derivatives.
- Yu, Richard H.,Polniaszek, Richard P.,Becker, Mark W.,Cook, Charles M.,Yu, Lok Him L.
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p. 972 - 980
(2012/12/30)
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- PROCESS FOR PREPARATION OF HIV PROTEASE INHIBITORS
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A process for the synthesis of bisfuran intermediates useful for preparing antiviral HIV protease inhibitor compounds is hereby disclosed.
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Page/Page column 30-31
(2008/06/13)
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- Novel P1 chain-extended HIV protease inhibitors possessing potent anti-HIV activity and remarkable inverse antiviral resistance profiles
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A novel series of tyrosine-derived HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and two protease inhibitor-resistant viruses. All of the compounds had wild-type antiviral activities that were similar to or greater than several currently marketed HIV protease inhibitors. In addition, a number of compounds in this series were more potent against the drug-resistant mutant viruses than they were against wild-type virus.
- Miller, John F.,Brieger, Michael,Furfine, Eric S.,Hazen, Richard J.,Kaldor, Istvan,Reynolds, David,Sherrill, Ronald G.,Spaltenstein, Andrew
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p. 3496 - 3500
(2007/10/03)
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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 126
(2010/02/12)
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- Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains
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A novel series of P1′ chain-extended arylsufonamides was synthesiszed and evaluated for wild-type HIV protease inhibitory activity and in vitro antiviral activity against wild type virus and two protease inhibitor-resistant mutant viruses. All of the comp
- Miller, John F.,Furfine, Eric S.,Hanlon, Mary H.,Hazen, Richard J.,Ray, John A.,Robinson, Laurence,Samano, Vicente,Spaltenstein, Andrew
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p. 959 - 963
(2007/10/03)
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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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- Evaluation of furofuran as a P2 ligand for symmetry-based HIV protease inhibitors
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The hexahydrofurofuranyloxy group was evaluated as a conformationally constrained P2 ligand for symmetry-based HIV protease inhibitors. A number of compounds showed nM level activity against HIV in MT4 cells and lower protein binding than the licensed protease inhibitor ritonavir. However, replacement of 5-thiazole of ritonavir with a furofuran caused a reduction of the bioavailability in vivo.
- Chen, Xiaoqi,Li, Lin,Kempf, Dale J.,Sham, Hing,Wideburg, Norman E.,Saldivar, Ayda,Vasavanonda, Sudthida,Marsh, Kennan C.,McDonald, Edith,Norbeck, Daniel W.
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p. 2847 - 2852
(2007/10/03)
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