Table 2. Enzyme Inhibition, Parasite Viability, and Microsomal Stability of Compound 2^a.

			IC50 (nM)				predicted CLb (mL/min/kg)
compd	R	R1	PfDHODH	HsDHODH	3D7	Dd2	H	M	cLogP
2a	4-Me	Me	39 (n = 4)	>30000	10 (n = 4)	22 (n = 4)	10	66	3.9
2b	5-Me		56		87	130	8	>72	3.9
2c	6-Me		56		33	74	10	>72	3.9
2d	7-Me		609		143	290	6	>72	3.9
2e	5-OCF3		22 (n = 4)		7 (n = 4)	9 (n = 4)	7	43	4.7
2f	6-OCF3		52 (n = 2)		36 (n = 2)	53 (n = 2)	10	41	4.7
2g	5-CF3		28		20	28	4	>72	4.3
2h	6-CF3		92		56	96	8	68	4.3
2i	4-OMe		162		49	109	4	>72	3.6
2j	4-OCHF2		44 (n = 6)		19 (n = 6)	26 (n = 6)	4	33	4.1
2k	4-OCH2CHF2		28		128	113	na	na	4.2
2l	4-F		34 (n = 2)		8 (n = 2)	6 (n = 2)	<4	37	3.5
2m	6-F		111		93	113	<4	>72	3.5
2n	4-Cl		21 (n = 2)		5 (n = 2)	6 (n = 2)	<4	19	4.1
2o	5-Cl		49		78	102	na	na	4.1
2p	4-Br		21 (n = 2)		4 (n = 2)	7 (n = 2)	5	26	4.3
2q	4-CN		40 (n = 9)		7 (n = 4)	10 (n = 4)	<4	26	2.9
2r	4-NMe2		181		75	159	na	na	3.9
2s	4-F, 6-Me		32		10	17	12	>72	4.0
2t	4-F, 6-Me	H	17	3100	4	4	10	>72	3.5
2u	4-Cl, 6-F	Me	25	>30000	12	13	5	42	4.3
2v	4-Cl, 6-F	H	35	5600	8	18	7	>72	3.8
2w	5-Me, 7-F	H	95	7300	36	60	11	>72	3.5
2x	5-CF3	H	19	17200	12	12	8	>72	3.8
2y	4-F	H	62	14900	17	8	10	>72	3.0

^aAssay conditions reported in ref (10).

^bUsing microsomes and based on well-stirred model with no correction for microsomal or protein binding.