TABLE 2

Physicochemical properties of compounds 15–20 and percentage of dihydrodiol metabolites formed in incubations with HLMs


Compound	R₁	R₂	R₃	n	Solubility^a	Log D^a	pK_a^{^b}	Average % Diol in HLMs (Replicate 1, Replicate 2)^{^c}
					µM
15	Me	Me	Me	1	258	1.6	8.2	9.9 (10.0, 9.9)
16	Me	Me	Me	1	586	0.4	9.3	1.5 (0, 3.1)
17		Me	Me	1	950	0.8	8.2	2.3 (2.1, 2.5)
18	Me	Me	Me	2	612	1.6	8.9	3.1 (3.0, 3.1)
19	Me	H	Me	2	628	0.5	9.7	0.7 (0.7, 0.7)
20	Me	Me	H	2	587	1.0	8.9	0 (0, 0)

↵^a Solubility and logD_7.4 HPLC were measured as described previously (Boström et al., 2012).
↵^b Calculated values.
↵^c Diol levels were determined from duplicate incubations (60 minutes) of 10 µM substrate with HLMs, without NADPH. Diol metabolite levels are expressed as a percentage of the sum of parent + diol peak areas.