Table 1. In Vitro ADME Properties of 6 and Analogues.

compd	CYP3A4 inhibitiona (μM)	pKa b	glogDpH 7.4 f	aqueous solubility,g pH 2/6.5 (μg/mL)	predicted human EH h
16	N/A	5.4	4.2	>100/6.3	0.91
22	18	5.1/8.7c	>5.3	>100/3.1	0.87
24	N/A	5.4/4.6c	>5.3	12.5/<1.6	0.44
25	5.2	5.4/2.2c	4.9	>100/<1.6	0.88
27	>20	5.4/4.5c	>5.3	>100/<1.6	0.65
31	>20	5.4/4.6c	4.7	25/<1.6	0.69
33	12	5.4/2.7c	3.0	25/<1.6	0.47
6	>20	5.6/5.0d	>5.3	>100/<1.6	0.68
28	16	5.4/1.9d	4.8	25/<1.6	0.74
34	6.3	5.3d/1.8e	4.9	12.5/<1.6	0.63

^aHuman CYP3A4 inhibition (IC₅₀) determined in human liver microsomes using 6β-hydroxylation of testosterone as the probe reaction pathway; N/A = not available.

^bpK_a values calculated using JChem for Excel; pK_a refers to 3-pyridyl nitrogen unless otherwise indicated.

^cpK_a for piperidine nitrogen.

^dpK_a for 2-pyridyl nitrogen (R¹).

^epK_a for pyrimidinyl nitrogen.

^fPartition coefficient values of the test compounds were estimated by correlation of their chromatographic retention properties against the characteristics of a series of standard compounds with known partition coefficient values, at pH 7.4.

^gKinetic solubility at pH 2 and pH 6.5 determined by nephelometry.

^hMicrosome predicted hepatic extraction ratio (E_H) determined in human liver microsomes.