Table 2.

Activity data for C-ring variants against Plasmodium falciparum.

Compd[a]	R1	EC50[b] [μm]		cLog D[c]	Solubility [μm]	CLint[d]
		P. falc.	L6 cells	(pH 7.4)	water	[μL min mg−1 protein]
55	–	0.061	56	2.8	>125	n.d.
56	H	0.047	54	4.0	>125	69
57	CH3-	0.014	29	4.2	>125	286
58	CH3CH2	0.021	36	4.5	>125	381
59	CH3CH2CH2	0.15	34	4.7	n.d.	n.d.
60		0.23	65	2.8	n.d.	n.d.
61	(CH3)2NCH2CH2-	0.25	35	2.4	n.d.	n.d.
62		0.23	43	5.5	n.d.	n.d.
63		0.046	54	5.9	89	n.d.
64		0.077	38	4.5	>125	n.d.

^[a]Overall yields: 50–90 %; reference compounds: chloroquine, EC₅₀=0.019–0.066 μm (P. falciparum K1); podophyllotoxin, EC₅₀=0.012 μm (L6 cells).

^[b]The EC₅₀ values are the mean of two independent assays, which varied less than ±50 %; n.d=not determined.

^[c]Calculated using StarDrop (http://www.optibrium.com).

^[d]Intrinsic clearance determined in vitro using mouse liver microsomes at the University of Dundee (UK).