Synthesis and Computational Analysis of New Antioxidant and Antimicrobial Angular Chromenopyrimidines

A convenient synthetic protocol for the synthesis of novel chromenopyrimidine derivatives based on angular scaffold has been developed from the readily available enaminonitrile precursor 1. The skeleton of chromenopyrimidines has been decorated with different moieties in order to approach compounds with improved antioxidant and antimicrobial activities. Compound 1 was reacted with Ac2O to yield benzochromenopyrimidine 6 that gave chloropyrimidine 7 via chlorination reaction. The reaction of chloropyrimidine 7 with different amines afforded a series of benzochromenopyrimidines 9-12. The hydrazine 11 and hydrazide 13 derivatives showed excellent antioxidant activity in addition to the potent antimicrobial activity revealed by aminopyrimidines 10 and 16. Computational docking studies indicated the potential recognition of compound 13 towards antioxidant binding site. Dual evaluations of the antimicrobial affinity of compound 16 indicated its promising activity as antimicrobial lead.