Title:Aminoimidazo[1,2-a]pyridine Bearing Different Pyrazole Moieties as the
Structural Scaffold for the Development of BACE1 Inhibitor; Synthesis,
Structural Characterization, in vitro and in silico Studies
Volume: 19
Issue: 6
Author(s): Seyed Esmaeil Sadat Ebrahimi, Aida Iraji, Kourosh Jelveh, Ali Moazzam, Saeed Bahadorikhalili, Azadeh Yahya‐Meymandi, Bagher Larijani, Mahmmod Biglar, Najmeh Edraki and Mohammad Mahdavi*
Affiliation:
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute,
Tehran University of Medical Sciences, Tehran, Iran
Keywords:
Aminoimidazo[1, 2-a]pyridine, BACE1 inhibitor, docking, Alzheimer’s disease, pyrazole, synthesis.
Abstract: Regarding the critical role of amyloid-β plaques in the pathogenesis of Alzheimer's
disease, a series of aminoimidazo[1,2-a]pyridine derivatives were designed and synthesized as
potential anti-BACE1 agents targeting the production of amyloid-β plaques. In vitro biological
results demonstrated that compounds 7b and 7f exhibited the best inhibitory potency against
BACE1 with IC50 values of 22.48 ± 2.06 and 30.61 ± 3.48 μM, respectively. Also, the ligandprotein
docking evaluations revealed that compounds 7b and 7f could effectively bind with the
different pockets of BACE1 through different interactions with the residue of the active site. The
results of current studies underline the potential role of aminoimidazo[1,2-a] pyridine-containing
pyrazole derivatives for developing novel BACE1 inhibitors.