Extending the Library of 4-Hydroxycoumarin Derivatives with Potential Pharmacological Activity by a Catalyst-Free and Purification-Free Method

摘要

Constant mutations of SARS-CoV-2 from 2019 to the present commences potential dilemma to the efficacy of developed COVID-19 antiviral drugs. In this current report, series of 3- phenyl(alkylamino)methyl-4-hydroxycoumarin was identified as compounds of drug-likeliness that, through molecular docking simulations, also demonstrated favourable binding to different sites of the SARS-CoV-2 RBD/hACE2 complex. This was achieved by varying the chain of the alkyl length and the substituent of the phenyl moiety. The subjected 3-phenyl(alkylamino)methyl- 4-hydroxycoumarin compounds were successfully synthesized by a catalyst-free multicomponent condensation reaction of 4- hydroxycoumarin, p-substituted benzaldehyde, and linear alkyl amines in dichloromethane (DCM) at 22°C. The crude products were achieved in a moderate (40–50) to a very good (80– 90) yield with excellent purity without the need for chemical purification verified by nuclear magnetic resonance (NMR) spectroscopy. The simple method to produce 3- phenyl(alkylamino)methyl-4-hydroxycoumarin and the preliminary docking results present an opportunity for advancement in drug discovery.