Rational design of novel benzisoxazole derivatives with acetylcholinesterase inhibitory and serotoninergic 5-HT 4 receptors activities for the treatment of Alzheimer’s disease

Chemistry

All commercially available compounds were used without further purification. Melting points were determined on a Köfler apparatus. Analytical thin-layer chromatography (TLC) was performed on silica gel 60 F₂₅₄ on aluminium plates (Merck) and visualized with UV light (254 nm). Flash chromatography was conducted on a VWR SPOT II Essential instrument with silica gel 60 (40–63 µm). Column’s size and flow rate were used according to manufacturer’s recommendation. NMR spectra were recorded at 400 or 500 MHz (Bruker Avance III 400/500 MHz) for ¹H NMR and at 100 or 125 MHz for ¹³C NMR in chloroform-d, methanol-d₄ or DMSO-d₆ with chemical shift (δ) given in parts per million (ppm) relative to TMS as internal standard and recorded at 295 K. The following abbreviations are used to describe peak splitting patterns when appropriate: br = broad, s = singlet,…