Quinazolinone fungal efflux pump inhibitors. Part 3: (N-methyl)piperazine variants and pharmacokinetic optimization

Further structure–activity relationships of a novel series of fungal efflux pump inhibitors with respect to potentiation of the activity of fluconazole against strains of C. albicans and C. glabrata over-expressing ABC-type efflux pumps are systematically explored. Rat protein binding and pharmacokinetics of selected analogues are reported.

Graphical abstractFurther structure–activity relationships of a novel series of fungal efflux pump inhibitors with respect to potentiation of the activity of fluconazole against strains of Candida albicans and Candida glabrata over-expressing ABC-type efflux pumps are systematically explored. Rat protein binding, hepatocyte stability, and pharmacokinetics of selected analogues are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide