Carbazole-containing arylcarboxamides as BACE1 inhibitors
Copyright policy )Carbazole-containing arylcarboxamides as BACE1 inhibitors
β-Secretase (BACE1) is widely recognized as a prime drug target for the treatment of Alzheimer's disease (AD). In this Letter, we report the synthesis and the BACE1 inhibitory activity of novel, variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylcarboxamides. The best results have been obtained with the introduction of a 4-OMe substituent (IC(50)=3.8 μM) or a 3,4-dichloro substituent (IC(50)=2.5 μM) in the amidic aromatic ring. The blood-brain barrier penetration predictions resulted to be promising for this type of compounds. To better understand the structure-activity relationships (SAR) of the new derivatives, a docking study procedure has been applied exploiting different conformational and ionic states of BACE1.
- University of Padua Italy
- University of Pisa Italy
- University of Hertfordshire United Kingdom
- Lundbeck Germany
Models, Molecular, Carbazoles, Amides, Structure-Activity Relationship, Alzheimer Disease, Blood-Brain Barrier, Aspartic Acid Endopeptidases, Humans, Amyloid Precursor Protein Secretases, Enzyme Inhibitors, Protein Binding
Models, Molecular, Carbazoles, Amides, Structure-Activity Relationship, Alzheimer Disease, Blood-Brain Barrier, Aspartic Acid Endopeptidases, Humans, Amyloid Precursor Protein Secretases, Enzyme Inhibitors, Protein Binding
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