N‐(2‐(Piperazin‐1‐yl)phenyl)arylamide Derivatives as β‐Secretase (BACE1) Inhibitors: Simple Synthesis by Ugi Four‐Component Reaction and Biological Evaluation

Abstract

A novel series of N-(2-(piperazin-1-yl)phenyl)aryl carboxamide derivatives were simply synthesized by Ugi-multicomponent reaction as β-secretase (BACE1) inhibitors. The BACE1 inhibitory activity of the synthesized compounds was examined using a Forester resonance energy transfer (FRET)-based assay. Among the tested compounds, the N-(5-bromo-2-(4-phenylpiperazine-1-yl)phenyl)thiophene-carboxamide derivative 14 containing the N-cyclohexyl indole acetamide moiety showed superior BACE1 inhibition at 10 and 40 µM. The results of the molecular docking study indicated that compound 14 establishes favorable hydrogen bonding interactions with the catalytic amino acid residues Asp228 and Thr72 and could be well accommodated in the flap region and P2 and P'2 pockets of the BACE1 active site.

Usage of Quantum Chemical Methods to Understand the Formation of Concomitant Polymorphs of Acetyl 2-(N-(2-Fluorophenyl)imino)coumarin-3-carboxamide

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Novel N‐benzylpiperidine derivatives of 5‐arylisoxazole‐3‐carboxamides as anti‐Alzheimer's agents

“…The kit was purchased from Invitrogen (former Pan Vera Corporation) and the evaluation procedure was conducted according to the manufacturer's instructions. [ 24–26 ] BACE1 (purified baculovirus‐expressed enzyme) was diluted using buffer (50 mM sodium acetate, pH 4.5) to prepare a 3× working solution of 1 U/ml. The peptide substrate (RhEVNLDAEFK‐Quencher) was also diluted in the same buffer to obtain the 3× stock solution.…”

Design, synthesis, in vitro and in silico studies of novel Schiff base derivatives of 2‐hydroxy‐4‐methoxybenzamide as tyrosinase inhibitors

“…To choose and validate the docking algorithm, the tropolone as cognate ligand inside the 2Y9X was redocked. Finally, the best docking confirmations with minimum binding energy were visualized using Discovery studio (Edraki et al, 2015).…”