136630-87-0Relevant 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.
Stereoselective synthesis of erythro α-amino epoxides
Rotella, David P.
, p. 5453 - 5456 (2007/10/02)
The stereoselective reduction of bromomethyl ketones derived from leucine, phenylalanine, alanine and valine is described using borohydride reagents. The Boc-amino alcohol product has erythro stereochemistry at the carbinol center as deduced by conversion to Boc-amino epoxides. These oxiranes are useful for the preparation of hydroxyethylene peptide isosteres.
Substrate Analogue Renin Inhibitors Containing Replacements of Histidine in P2 or Isosteres of the Amide Bond between P3 and P2 Sites
Raddatz, Peter,Jonczyk, Alfred,Minck, Klaus-Otto,Schmitges, Claus Jochen,Sombroek, Jan
, p. 3267 - 3280 (2007/10/02)
Incorporation of β-alanine or γ-aminobutyric acid in position P2 of ACHPA or LeuΨVal-based tetrapeptides gave highly active renin inhibitors (compounds V,VI, and XVII) with high specificity for renin and a remarkable stability against chymotrypsin.Replacement of the amide bond between P2 and P3 by isosteres (ketomethylenes, hydroxyethylenes, and the corresponding thio-insertion analogues) led to compounds (VIII-XIII, XVIII, and XIX) with renin inhibitory activity in the nanomolar range.Oral activity was achieved by incorporation of polar functionalities at the N-terminus of β-alanine-containing tetrapeptides.One of these compounds (XXVIII) was chosen for further studies.This inhibitor demonstrated excellent efficacy and a long duration of action after intravenous and oral administration to cynomolgus monkeys.
