β-Secretase (BACE1, β-site APP cleaving enzyme) is one of the most challenging therapeutic targets in the field of Alzheimer's disease (AD) research. This enzyme catalyses the formation of neuronal amyloid β (A β) plaques, whose increased production is a key event in the initial pathogenesis of AD. As a consequence, many BACE1 inhibitors have been developed by several research groups. In the present work, after an analysis of tetraline derivatives reported in a Takeda patent, we designed and synthesized some analogues, making appropriate structural modifications, in order to try to improve the bioavailability features and the activities of Takeda compounds. All the new derivatives were tested on BACE1 with the TR-FRET (Time Resolved-Fluorescence Resonance Energy Transfer) technology and one of them showed a promising inhibitory activity value.
Biphenyl-Derivatives Possessing Tertiary Amino Groups as ß-Secretase (BACE1) Inhibitors
BERTINI, SIMONE;GRANCHI, CARLOTTA;MINUTOLO, FILIPPO;MACCHIA, MARCO
2010-01-01
Abstract
β-Secretase (BACE1, β-site APP cleaving enzyme) is one of the most challenging therapeutic targets in the field of Alzheimer's disease (AD) research. This enzyme catalyses the formation of neuronal amyloid β (A β) plaques, whose increased production is a key event in the initial pathogenesis of AD. As a consequence, many BACE1 inhibitors have been developed by several research groups. In the present work, after an analysis of tetraline derivatives reported in a Takeda patent, we designed and synthesized some analogues, making appropriate structural modifications, in order to try to improve the bioavailability features and the activities of Takeda compounds. All the new derivatives were tested on BACE1 with the TR-FRET (Time Resolved-Fluorescence Resonance Energy Transfer) technology and one of them showed a promising inhibitory activity value.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
