Microwave assisted synthesis, acetylcholinesterase inhibition and molecular docking studies of furo[2,3-d]pyrido[1,2-a]pyrimidin-4-one derivatives

Abstract

A series of phenyl, substituted phenyl and thiophene bearing dihydrofuropyrimidin-4-ones (3a-p) were synthesized by Mn(OAc)₃ mediated, microwave irradiated radical cyclizations of 2-hydroxy-pyridopyrimidin-4-one derivatives (1a-j) with substituted phenylvinylthiophenes (2a-c) at 70°C in 2 min. Compounds 3a-j was obtained between 28% and 66% yields. Molecular structures of 3a-p were determined by ¹H NMR, ¹³C NMR, ¹⁹F NMR, FTIR and HRMS techniques. Inhibitory activity of 3a-p were evaluated against Acetylcholinesterase (AChE) and inhibition results of these compounds showed that the compounds had good inhibition with IC₅₀ values between 0.52 and 3.77 μM. In addition, molecular docking studies were carried out on the most potent inhibitory compounds 3d (IC₅₀ = 0.64 μM), 3p (IC₅₀ = 0.52 μM) and standart drug Donepezil. The binding energies for 3d, 3p and Donepezil are −9.12, −10.08 and −12.65 Kcal/mol, respectively. Based on these results, it was determined that, compounds 3d and 3p are promising AChE inhibitors.