388071-41-8Relevant academic research and scientific papers
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.
Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human β-secretase
Maillard, Michel C.,Hom, Roy K.,Benson, Timothy E.,Moon, Joseph B.,Mamo, Shumeye,Bienkowski, Michael,Tomasselli, Alfredo G.,Woods, Danielle D.,Prince, D. Bryan,Paddock, Donna J.,Emmons, Thomas L.,Tucker, John A.,Dappen, Michael S.,Brogley, Louis,Thorsett, Eugene D.,Jewett, Nancy,Sinha, Sukanto,John, Varghese
, p. 776 - 781 (2007/10/03)
The design and synthesis of a novel series of potent and cell permeable peptidomimetic inhibitors of the human β-secretase (BACE) are described. These inhibitors feature a hydroxyethyl secondary amine isostere and a novel aromatic ring replacement for the
