Table 2. SAR of analogues with N-(2,4-difluorophenylacetyl)piperidine RHS.

R	Compound	Ld InMac pEC50 a	THP-1 a pEC50	Aqueous solubility b μM	Cli mouse, c ml min–1 g–1
	11	<4.3	<4.3	27	22.0
	12	5.9	<4.3	39	5.0
	13	6.0	<4.3	78	0.5
	14	4.6	<4.3	ND d	<0.5
	15	6.1	<4.3	14	2
	16	5.2	<4.3	33	ND d
	17	6.5	<4.3	<1	7.2
	18	6.1	<4.3	23	6.7
	19	5.5	4.7	30	3.3
	20	7.1	4.4	<1	5.0
	21	7.1	<4.3	25	15

^aLd InMac is the intramacrophage assay carried out in THP-1 cells with L. donovani amastigotes.9 Data are the mean values for n ≥ 3 replicates and standard deviations are ≤0.4.

^bAq. solubility is kinetic aqueous solubility (CAD).11

^cCl_i is mouse liver microsomal intrinsic clearance.10

^dND means not determined.