Design, synthesis and docking studies of Hydroxyethylamine and Hydroxyethylsulfide BACE-1 inhibitors.
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.
Rizzi
Luca
L
Institute of Medicinal Chemistry "Pietro Pratesi", School of Pharmacy, University of Milan, Via Mangiagalli 25, 20133, Milan, Italy.
Vaiana
Nadia
N
Sagui
Francesca
F
Genesio
Eva
E
Pilli
Elena
E
Porcari
Valentina
V
Romeo
Sergio
S
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
D005021:Ethylamines; D011480:Protease Inhibitors; D013438:Sulfhydryl Compounds; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human