- Intermediate reaches reed that Wei new synthetic process of the
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The invention provides a novel synthesis process of Darunavir intermediate, N-tertbutyloxycarbonyl-L-phenylalanine is used as a raw material, esterification, condensation, reduction, hydrogenation and reduction amination, and other reactions are carried out for preparing the key intermediate of Darunavir: (2R,3S)-3-(tert-butyloxycarbonyl)amino-1-[(2-methyl propyl)amino]-4-phenyl-2-butanol. The new synthesis process of Darunavir intermediate has the advantages of mild reaction condition, simple operation, and high reaction selectivity and yield, and the process is suitable for industrial production.
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- INDOLE COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSIS
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The present invention relates to new indole compounds, pharmaceutically acceptable salts or isomers thereof which are useful for the prevention or treatment of cellular necrosis and necrosis-associated diseases. The present invention also relates to a method and a composition for the prevention or treatment of cellular necrosis and necrosis-associated diseases, comprising said indole compounds as an active ingredient.
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Page/Page column 28
(2010/08/22)
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- BETA-SECRETASE INHIBITING COMPOUNDS HAVING OXO-DIHYDRO-PYRAZOLE MOIETY
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Disclosed are compounds represented by Formula (I) as defined in the specification, or pharmaceutically acceptable salts or isomers thereof, and a pharmaceutical composition for inhibiting beta-secretase activity comprising a therapeutically effective amo
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Page/Page column 34; 21
(2009/04/25)
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- INDOLE COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSIS
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The present invention relates to new indole compounds, pharmaceutically acceptable salts or isomers thereof which are useful for the prevention or treatment of cellular necrosis and necrosis-associated diseases. The present invention also relates to a method and a composition for the prevention or treatment of cellular necrosis and necrosis-associated diseases, comprising said indole compounds as an active ingredient.
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Page/Page column 91-92
(2009/04/25)
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- BETA-SECRETASE INHIBITING COMPOUNDS
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Disclosed are compounds represented by Formula (I) as defined in the specification, or pharmaceutically acceptable salts or isomers thereof, and a pharmaceutical composition for inhibiting beta-secretase activity comprising a therapeutically effective amount of the same.
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Page/Page column 54-55
(2009/04/25)
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- BACE-1 inhibitors part 2: Identification of hydroxy ethylamines (HEAs) with reduced peptidic character
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This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Dependi
- Clarke, Brian,Demont, Emmanuel,Dingwall, Colin,Dunsdon, Rachel,Faller, Andrew,Hawkins, Julie,Hussain, Ishrut,MacPherson, David,Maile, Graham,Matico, Rosalie,Milner, Peter,Mosley, Julie,Naylor, Alan,O'Brien, Alistair,Redshaw, Sally,Riddell, David,Rowland, Paul,Soleil, Virginie,Smith, Kathrine J.,Stanway, Steven,Stemp, Geoffrey,Sweitzer, Sharon,Theobald, Pam,Vesey, David,Walter, Daryl S.,Ward, John,Wayne, Gareth
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p. 1017 - 1021
(2008/09/20)
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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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- HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE
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The present invention relates to novel hydroxyethylamine compounds of formula (I): (I) having Asp2 (-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated-amyloid levels or-amyloid deposits, particularly Alzheimer's disease.
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- TRICYCLIC INDOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF ALZHEIMER’S DISEASE
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The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β- amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.
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- Structure-based design of potent and selective cell-permeable inhibitors of human β-secretase (BACE-1)
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We describe the development of cell-permeable β-secretase inhibitors that demonstratively inhibit the production of the secreted amino terminal fragment of an artificial amyloid precursor protein in cell culture. In addition to potent inhibition in a cell
- Stachel, Shawn J.,Coburn, Craig A.,Steele, Thomas G.,Jones, Kristen G.,Loutzenhiser, Elizabeth F.,Gregro, Alison R.,Rajapakse, Hemaka A.,Lai, Ming-Tain,Crouthamel, Ming-Chih,Xu, Min,Tugusheva, Katherine,Lineberger, Janet E.,Pietrak, Beth L.,Espeseth, Amy S.,Shi, Xiao-Ping,Chen-Dodson, Elizabeth,Holloway, M. Katharine,Munshi, Sanjeev,Simon, Adam J.,Kuo, Lawrence,Vacca, Joseph P.
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p. 6447 - 6450
(2007/10/03)
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- re- and si-face-selective nitroaldol reactions catalyzed by a rigid chiral quaternary ammonium salt: A highly stereoselective synthesis of the HIV protease inhibitor amprenavir (Vertex 478)
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Either amprenavir (1) or its C(2) diastereomer can be synthesized in a simple way by the use of a nitroaldol reaction carried out in the presence of one or the other of the two ammonium ions 2. The 1,3-diamino-2-hydroxypropyl structural element of 1 is also found in many other peptidomimetics and HIV protease inhibitors. Described here is a new strategy for possible application to direct and stereocontrolled synthesis of such compounds.
- Corey,Zhang, Fu-Yao
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p. 1931 - 1934
(2007/10/03)
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- A facile synthesis of (2R,3S)-1-amino-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutane; A useful component block of HIV protease inhibitor
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(S)-3-tert-Butoxycarbonylamino-1-nitro-2-oxo-4-phenylbutane 4 was converted to (2R,3S)-1-amino-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutane 5a by a catalytic hydrogenation, or NaBH4-TiCl4 reduction followed by hydrogenation in favorable diastereoselectivity, a component of the HIV protease inhibitor VX-478.
- Yuasa, Yoko,Yuasa, Yoshifumi,Tsuruta, Haruki
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p. 395 - 401
(2007/10/03)
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- Retrocarbamate protease inhibitors
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The invention discloses compounds of the formula STR1 are disclosed as HIV protease inhibitors.
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- Aminodiol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR
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A series of HIV protease inhibitors containing a novel C2 symmetrical "aminodiol" core structure were prepared from amino acid starting materials.The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds.Optimization of the structure-activity in this series led to aminodiol 9a (Ki = 100 nM; ED50(HIV-1) = 80 nM) containing P1/P1' benzyl and P2/P2' Boc substituents.Compound 9a is a selective inhibito r of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin.In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs.After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40percent) and a promising plasma elimination half-life (4 h).
- Barrish, Joel C.,Gordon, Eric,Alam, Masud,Lin, Pin-Fang,Bisacchi, Gregory S.,et al.
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p. 1758 - 1768
(2007/10/02)
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