Table 2. Physicochemical Properties and Activity Data of TCMDC-135051 Ring B Analogues.

			PfCLK3		3D7
analogue	R1	R2	IC50 (nM)a	pIC50	ED50 (nM)b	pEC50	log D7.4c	Clint (mL/min/g liver)d
28	CH3	CO2H	24	7.6 (±0.10)	1185	5.6 (±0.097)	0.66	1.33
29	H	CO2H	34	7.5 (±0.089)	3272	5.5 (±0.124)	0.65	11.01
30	CH(CH3)2	1H-tetrazole	19	7.7 (±0.089)	270	6.6 (±0.158)	0.93	2.32
31	CH(CH3)2	H	1300	6.0 (±0.091)	NDe	NDe	4.45	9.54
9	CH(CH3)2	CO2CH2CH3	390	6.4 (±0.087)	NDe	NDe	2.45	16.06
32	CO2H	CH(CH3)2	1385	4.9 (±0.093)	NDe	NDe	NDe	NDe

^aIC₅₀ (the concentration of an inhibitor where the response is reduced by half).

^bEC₅₀ (the concentration of a drug that gives half-maximal response). IC₅₀ and EC₅₀ values are means ± SEM of three independent experiments run in triplicates (n = 3).

^clog D_7.4 (distribution co-efficient) was estimated using HPLC chromatography.

^dIn vitro intrinsic clearance in mouse liver microsomes.

^eND, not determined.