Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure-based design and in vivo reduction …

…, L Jacobson, M Staufenbiel, S Desrayaud…

Index: Rueeger, Heinrich; Lueoend, Rainer; Rogel, Olivier; Rondeau, Jean-Michel; Moebitz, Henrik; MacHauer, Rainer; Jacobson, Laura; Staufenbiel, Matthias; Desrayaud, Sandrine; Neumann, Ulf Journal of Medicinal Chemistry, 2012 , vol. 55, # 7 p. 3364 - 3386

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Citation Number: 37

Abstract

Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime-and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure–activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the ...