Fig. 23
From: The past, present and future of anti-malarial medicines
Key stages in the hit to lead pathway of ACT-451840. Initial change of the n-pentyl group to an acylpiperazine (A′2) helped to improve the physicochemical properties. Subsequent introduction of a tert-butyl in place of the trifluoromethyl (A′3) and a cyano group on the southern phenyl ring resulted in the optimized compound