One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
Jessica Bais, Fabio Benedetti, Federico Berti, Iole Cerminara, Sara Drioli, Maria Funicello, Giorgia Regini, Mattia Vidali, Fulvia Felluga
Abstract
A library of dihydropyrimidinones was synthesized via a “one-pot” three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydrochloride, respectively. The products were screened in vitro for their β-secretase inhibitory activity. The majority of the compounds resulted to be active, with IC50 in the range 100 nM–50 μM.
Topics & Concepts
ThioureaBiginelli reactionGuanidineUreaChemistryIC50In vitroHydrochlorideOne-pot synthesisCombinatorial chemistryOrganic chemistryBiochemistryCatalysisMulticomponent Synthesis of HeterocyclesSynthesis and biological activitySynthesis of Organic Compounds