Design, synthesis & evaluation of condensed 2H-4-arylaminopyrimidines as novel antifungal agents

•A novel scaffold designed for antifungal activity.•Design based on favorable docking interactions at active site of fungal CYP51.•Good antifungal activity against three pathogenic fungal strains.•Good correlation between docking scores and antifungal activity; SAR been proposed.

A small, focussed library of condensed 2H-4-arylaminopyrimidines, with 3-diversity points, based on an initial design by molecular docking study of this scaffold at the active site of the fungal enzyme of cytochrome P450 family, lanosterol 14α-demethylase (CYP51) was synthesized through a one-pot green chemical synthetic protocol. The screening of the synthesised compounds for antifungal activity against Candida albicans, Aspergillus fumigatus & Aspergillus niger revealed activity in many of the compounds as comparable to that of fluconazole. Based on the antifungal activity and physicochemical property data of these derivatives, a meaningful SAR has been proposed.

Graphical abstractA library of designed condensed 2H-4-arylaminopyrimidines, synthesized under microwave irradiation showed antifungal activty comparable to that of fluconazole and a meaningful SAR has been developed.Figure optionsDownload full-size imageDownload as PowerPoint slide