Design, Green Synthesis, and Biological Evaluation of New Substituted Tetrahydropyrimidine Derivatives as Acetylcholinesterase Inhibitors

• Published in: Polycyclic aromatic compounds Vol. 42; no. 8; pp. 5231 - 5241
• Main Authors: Mariki, Ali akbar, Anaeigoudari, Akbar, Zahedifar, Mahboobeh, Pouramiri, Behjat, Ayati, Adileh, Lotfi, Safa
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 14-09-2022; Taylor & Francis Ltd
• Subjects: Acetylcholinesterase; Alzheimer's disease; butyrylcholinesterase inhibitors; Chemical synthesis; Donepezil; Inhibitors; NMR; Nuclear magnetic resonance; Substitutes; tetrahydropyrimidin-4-yl)pyridine
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406638.2021.1933102

A series of novel tetrahydropyrimidin-4-yl)pyridine derivatives 6(a-h) have been designed and synthesized as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The chemical structures of all newly synthesized compounds were characterized by spectroscopic methods (IR,
1
H NMR,
13
C NMR) and elemental analyzes. The in vitro studies showed that all the synthesized derivatives showed significant BChE inhibitory activity more potent than donepezil as the standard (IC
50
values less than 0.1 µM). All the target compounds demonstrated good AChE inhibitory effects comparable with donepezil as the reference drug with IC
50
values ranging from 0.08 to 0.1 µM. The best results were obtained by 4-methyl substituted derivative 6d with IC
50
value of 0.082 µM which was comparable with AChE inhibitory effects of donepezil (IC
50
 = 0.079 µM).