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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Letter Article

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

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*

Volume 19, Issue 6, 2022

Published on: 10 May, 2022

Page: [685 - 692] Pages: 8

DOI: 10.2174/1570179419666220126113014

Price: $65

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.

Keywords: Aminoimidazo[1, 2-a]pyridine, BACE1 inhibitor, docking, Alzheimer’s disease, pyrazole, synthesis.

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