Malononitrile-activated synthesis and anti-cholinesterase activity of styrylquinoxalin-2(1<i>H</i>)-ones

Abstract

Herein, we report a base-free malononitrile activated condensation of 3-methylquinoxaline-2(1<i>H</i>)-one (3MQ) 1 with aryl aldehydes 3a-3ad for synthesis of styrylquinoxalin-2(1<i>H</i>)-ones (SQs) 4a-4ad with excellent yields. In this reaction, malononitrile activates the aldehyde <i>via</i> Knoevenagel condensation towards reaction with 3MQ 1 and gets liberated during the course of reaction to yield the desired SQs 4a-4ad. The SQs were evaluated for <i>in vitro</i> cholinesterase inhibition and 4n was found to display a mixed type of inhibition of AChE, which was supported by molecular modelling studies. This study has led to the discovery of a new chemotype for cholinesterase inhibition which might be useful in finding a remedy for Alzheimer's disease.