Design, synthesis and docking studies of Hydroxyethylamine and Hydroxyethylsulfide BACE-1 inhibitors
Luca Rizzi1, Nadia Vaiana, Francesca Sagui
1Institute of Medicinal Chemistry "Pietro Pratesi", School of Pharmacy, University of Milan, Via Mangiagalli 25, 20133, Milan, Italy.
Abstract:
Both stereoisomer of hydroxyethylamine (HEA) and hydroxyethylsulfide (HES) transition-state isostere inhibitors of BACE-1 were synthesized. The syn-HEA epimer resulted always more active than the anti stereoisomer independently from the P(1) and the P(1)' substituents. On the contrary, the anti epimer of the HES isostere resulted more active than the syn stereoisomer. The change of stereopreference was studied by molecular modelling.
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