Table 4.

In Vitro ADME Properties of Compounds 7, 1c, 2l, 3c, 3j, 3l, 3p, 3s, 3v and 4b

ADME Properties	7	1c	2l	3c	3j	3l	3p	3s	3v	4b
Solubility in PBS at pH 4.0 (μM)	315	290	286	279	271	296	281	286	282	281
Solubility in PBS at pH 7.4 (μM)	315	302	295	286	283	292	278	293	288	288
Human Plasma Protein Binding (% bound)	33	91	71	80	78	74	93	65	52	68
Rat Plasma Protein Binding (% bound)	30	77	65	79	71	68	90	70	49	57
Mouse Plasma Protein Binding (% bound)	40	83	85	83	79	77	92	69	53	60
CYP1A2 Inhibition at 10 μM (%)	7.9	2.0	9.0	21.4	0.2	24.4	0.2	− 1.6	17.3	15.9
CYP2C9 Inhibition at 10 μM (%)	9.6	43.5	5.0	8.9	6.2	7.1	37.6	11.7	10.7	10.5
CYP2C19 Inhibition at 10 μM (%)	37.0	− 1.1	− 4.9	3.9	0.7	1.6	− 2.5	− 4.4	14.2	2.8
CYP2D6 Inhibition at 10 μM (%)	1.2	9.1	2.5	12.8	10.3	11.4	3.4	8.7	9.1	11.0
CYP3A4 Inhibition 1a at 10 μM (%)	21.0	2.5	21.2	28.7	− 2.3	10.9	− 18.5	12.1	6.6	8.6
CYP3A4 Inhibition 2 at 10 μM (%)	20.5	4.2	3.1	2.3	− 2.3	− 1.9	3.2	− 2.4	3.3	0.7
Caco-2 Permeability (Efflux Ratio)	2.9	2.9	3.9	2.3	2.4	4.7	2.3	3.9	2.3	2.4
Caco-2 Permeability (Recovery %, A-Bb)	82	55	69	70	67	59	51	61	71	66
Caco-2 Permeability (Recovery %, B-A)	117	76	97	95	91	83	79	92	93	91
Human LMc Stability (% @60min)	99	73	89	87	87	91	94	99	104	99
Rat LM Stability (% @60min)	98	80	90	81	91	79	81	98	91	97
Mouse LM Stability (% @60min)	104	77	92	96	104	91	92	92	97	87

^aCYP3A4 Inhibition 1, using midazolam as substrate; CYP3A4 Inhibition 2, using testosterone as substrate.

^bA-B = apical to basolateral; B-A = basolateral to apical.

^cLM = Liver Microsome.