362480-01-1Relevant articles and documents
Design, synthesis, and biological evaluation of novel fluorinated ethanolamines
Fustero, Santos,Cunat, Ana C.,Flores, Sonia,Baez, Claribel,Oliver, Judit,Cynamon, Michael,Guetschow, Michael,Mertens, Matthias D.,Delgado, Oscar,Tresadern, Gary,Trabanco, Andres A.
scheme or table, p. 14772 - 14784 (2012/02/03)
The preparation of novel fluorinated allylamines and their use as key fragments for the stereoselective synthesis of hydroxyethyl secondary amine (HEA)-type peptidomimetics is described. Our strategy employs chiral sulfinyl imines as synthesis intermediates, by treatment of hemiaminal precursors with two equivalents of vinylmagnesium bromide. The subsequent oxidation of the allylic amines to the corresponding epoxides was achieved by treatment with methyl(trifluoromethyl)dioxirane. Finally, epoxide ring opening with a range of nitrogen nucleophiles provided a library of HEA-derived peptidomimetics with a phenyldifluoromethylene moiety. The biological evaluation of these derivatives revealed compounds with remarkable BACE1 inhibitory activity. Docking studies revealed the influence of the fluorine atoms in the binding mode of the synthesized ligands. Furthermore, the biological evaluation of our final products and synthesis intermediates led to the discovery of compounds with antimicrobial activity against Mycobacterium and Nocardia species.
COMPOUNDS CONTAINING FUSED RINGS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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Page/Page column 108, (2011/11/01)
The invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.
Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind β-secretase in a N-terminal 10s-loop down conformation
Stauffer, Shaun R.,Stanton, Matthew G.,Gregro, Alison R.,Steinbeiser, Melissa A.,Shaffer, Jennifer R.,Nantermet, Philippe G.,Barrow, James C.,Rittle, Kenneth E.,Collusi, Dennis,Espeseth, Amy S.,Lai, Ming-Tain,Pietrak, Beth L.,Holloway, M. Katharine,McGaughey, Georgia B.,Munshi, Sanjeev K.,Hochman, Jerome H.,Simon, Adam J.,Selnick, Harold G.,Graham, Samuel L.,Vacca, Joseph P.
, p. 1788 - 1792 (2008/02/02)
A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P3 which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.
Amine, 1, 2-and 1, 3-diol, and its use for curing Alzheimer's disease
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Page/Page column 214, (2008/06/13)
Disclosed are compounds of formula: and pharmaceutically acceptable salts and esters thereof, useful in treating and/or preventing Alzheimer's disease and other similar diseases, wherein RN, RC, R1, n and R20 are defined herein. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.