Rizzi Luca, Vaiana Nadia, Sagui Francesca, Genesio Eva, Pilli Elena, Porcari Valentina, Romeo Sergio
Institute of Medicinal Chemistry "Pietro Pratesi", School of Pharmacy, University of Milan, Via Mangiagalli 25, 20133, Milan, Italy.
Protein Pept Lett. 2009;16(1):86-90. doi: 10.2174/092986609787049439.
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.
合成了羟乙胺（HEA）和羟乙硫醚（HES）这两种BACE-1的过渡态等排体抑制剂的立体异构体。无论P(1)和P(1)'取代基如何，顺式-HEA差向异构体总是比反式立体异构体更具活性。相反，HES等排体的反式差向异构体比顺式立体异构体更具活性。通过分子模拟研究了立体选择性的变化。
