Improved synthesis of antiplasmodial 4-aminoacridines and 4,9-diaminoacridines

Abstract

Acridines are one of the most important nitrogen-containing heterocycle systems and have many applications in the therapeutic field. However, the synthesis of acridine-based scaffolds is not always straightforward. Herein, we report the optimization of two multi-step synthetic routes towards 4,9-diaminoacridines and 4-aminoacridines, which have shown promising antiplasmodial properties. The improved synthesis pathways make use of greener, simpler, and more efficient methods, with less reaction steps and increased overall yields, which were doubled in some cases. These are impactful results towards future approaches to the chemical synthesis of acridine-based compounds.