Quinazolinone-based fungal efflux pump inhibitors. Part 1: Discovery of an (N-methylpiperazine)-containing derivative with activity in clinically relevant Candida spp.

ABSTRACT

The discovery of a series of quinazolinone-based fungal efflux pump inhibitors by high-throughput screening for potentiation of fluconazole in C. albicans is described. Attempts to improve the aqueous solubility of screening hits led to the discovery of an analog with greatly improved physical properties and activity against clinically-relevant Candida spp.