Table 3. Physicochemical and in Vitro Drug Metabolism and Pharmacokinetic Properties of Compounds 5–18^a.

compound number	log D	solubility at pH 7.4 (μM)	human liver microsome intrinsic clearance (μL/min/mg)	rat hepatocyte intrinsic clearance (μL/min/106 cells)	human hepatocyte intrinsic clearance (μL/min/106 cells)	caco-2 cell intrinsic permeability (106 cm/s)b	early dose to human prediction (mg/day)c
5	0.3	18	<3	<1	<1	0.89	150
6	0.9	140	4.5	11	<1	12	110
7	1.0	930	<3	19	<1	19	71
8	1.2	42	<3	3.2	3.2	6.0	180
9	1.7	8.3b	39	20	1.9	18	14
10	3.3	0.37	8.2	30	4.3	49	1000
11	2.0	3.3	<3	<1	<1	11	630
12	1.3	150	11	15	<1	19	290
13	1.1	210	3.3	21	<1	9.6	120
14	1.3	160	<3	2.4	<1	17	68
15	1.5	190	5.5	5.6	<1	19	49
16	1.2	270	<3	1.8	<1	11	8
17	1.4	850	<3	<1	<1	10	97
18	0.7	880	<3	<1	<1	1.3	15

^aUnless otherwise indicated, values are the mean of three replicates.

^bn = 2.

^cEarly dose to human predictions were based on a composite of myeloperoxidase (MPO) IC₅₀ and metabolic stability in human hepatocytes. A free steady state plasma level of 10 times MPO IC₅₀ was assumed as a requirement for functional efficacy in vivo (see the Supporting Information).