1345853-40-8Relevant articles and documents
Carbazole-containing arylcarboxamides as BACE1 inhibitors
Bertini, Simone,Asso, Valentina,Ghilardi, Elisa,Granchi, Carlotta,Manera, Clementina,Minutolo, Filippo,Saccomanni, Giuseppe,Bortolato, Andrea,Mason, Jonathan,Moro, Stefano,MacChia, Marco
, p. 6657 - 6661 (2011/12/04)
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 (IC50 = 3.8 μM) or a 3,4-dichloro substituent (IC50 = 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.