In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer’s disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC50 = 2.49 ± 0.08 μM), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series.
From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold / Angela, Rampa; Francesca, Mancini; Angela, De Simone; Federico, Falchi; Federica, Belluti; Rita Maria, Concetta Di Martino; Silvia, Gobbi; Vincenza, Andrisano; Andrea, Tarozzi; Manuela, Bartolini; Andrea, Cavalli; Alessandra, Bisi. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 25:(2015), pp. 2804-2808. [10.1016/j.bmcl.2015.05.002]
From AChE to BACE1 inhibitors: The role of the amine on the indanone scaffold
RAMPA, ANGELA;DE SIMONE, ANGELA;BELLUTI, FEDERICA;DI MARTINO, RITA MARIA CONCETTA;GOBBI, SILVIA;ANDRISANO, VINCENZA;TAROZZI, ANDREA;BARTOLINI, MANUELA;CAVALLI, ANDREA;BISI, ALESSANDRA
2015
Abstract
In recent years, a progressive increase in age-related disorders could be observed in most western countries, among which Alzheimer’s disease (AD) is one of the most challenging. BACE1 could be seen as an attractive target to develop disease-modifying compounds, and in this context, a new series of hybrid molecules was designed and synthesized, based on a previously identified multitarget lead compound. In particular, the amino side chain was appropriately modified to fit BACE1 as additional target. In vitro testing results pointed out compound 8 (IC50 = 2.49 ± 0.08 μM), bearing the bulky bis(4-fluorophenyl)methyl)piperazine substituent, as the most potent BACE1 inhibitor of the series.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
