Figure 5

Structures, IC90s, maximum whole and free brain concentrations, and residual 24 h plasma concentrations of diamine quinoline methanols. IC90s are expressed in ng/ml against the mefloquine-sensitive W2 strain of P. falciparum. Maximum whole and free brain concentrations in male FVB mice after iv dosing (5 mg/kg) are expressed in ng/g. Residual plasma concentrations at 24 h after iv dosing are expressed as a percentage relative to the 5 minute time point. One in 5 diamines (20%, WR308396) had acceptable potency. One in 5 diamines had acceptable whole (20%, WR319535) and free (20%, WR319535) brain levels relative to mefloquine. WR319535 exhibited a half-life longer than mefloquine after oral dosing (data not shown). For this reason we have assumed that the residual plasma concentrations at 24 h of all (100%) of the diamines may be indicative of long half-lives.