A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: Structure-based design, synthesis, and biological evaluation.
In this work, we report a rational structure-based approach aimed at the discovery of new 2-aminoimidazoles as β-secretase inhibitors. Taking advantage of a microwave-assisted synthetic protocol, a small library of derivatives was obtained and biologically evaluated. Two compounds showed promising activities in both enzymatic and cellular assays. Moreover, one of them exhibited the capability to cross the blood-brain barrier as assessed by the parallel artificial membrane permeability assay.
Statistical and Biological Physics Sector, SISSA-ISAS, Via Bonomea 265, 34136 Trieste, Italy.
Gianpaolo
G
Chiriano
Angela
A
De Simone
Francesca
F
Mancini
Daniel I
DI
Perez
Andrea
A
Cavalli
Maria Laura
ML
Bolognesi
Giuseppe
G
Legname
Ana
A
Martinez
Vincenza
V
Andrisano
Paolo
P
Carloni
Marinella
M
Roberti
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009474:Neurons; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D007093:Imidazoles; D054852:Small Molecule Libraries; D053829:Amyloid Precursor Protein Secretases