title: Design, synthesis and docking studies of Hydroxyethylamine and Hydroxyethylsulfide BACE-1 inhibitors.
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.
authors.affiliation: Institute of Medicinal Chemistry "Pietro Pratesi", School of Pharmacy, University of Milan, Via Mangiagalli 25, 20133, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Rizzi
authors.forename: Nadia
authors.initials: N
authors.lastname: Vaiana
authors.forename: Francesca
authors.initials: F
authors.lastname: Sagui
authors.forename: Eva
authors.initials: E
authors.lastname: Genesio
authors.forename: Elena
authors.initials: E
authors.lastname: Pilli
authors.forename: Valentina
authors.initials: V
authors.lastname: Porcari
authors.forename: Sergio
authors.initials: S
authors.lastname: Romeo
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D040761:Biomimetic Materials; D015195:Drug Design; D005021:Ethylamines / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005021:Ethylamines; D011480:Protease Inhibitors; D013438:Sulfhydryl Compounds; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human