Compound | R1 | R2 | R3 | n | Solubilitya | Log Da | pKaa | Average % Diol in HLMs (Replicate 1, Replicate 2)b |
---|---|---|---|---|---|---|---|---|
µM | ||||||||
1 | MeO | Me | H | 0 | 11 | 3.0 | 6.1 | 0 (0, 0) |
2 | H | H | H | 0 | 106 | 2.1 | 6.6 | 1.1 (1.2, 0.9) |
3 | MeO | H | H | 0 | 63 | 2.2 | 6.6 | 1.6 (1.6, 1.7) |
4 | H | H | Me | 1 | 858 | 2.3 | 8.4 | 15 (15, 15) |
5 | MeO | H | Me | 1 | NA | 2.0 | 8.2 | 16 (16, 16) |
6 | H | Me | Me | 1 | 80 | 4 | 8.5 | 91 (89, 92) |
7 | MeO | Me | Me | 1 | 70 | 4.1 | 8.0 | 89 (88, 89) |
8 | MeO | H | H | 1 | NA | 1.3 | NA | 2.7 (2.7, 2.8) |
9 | MeO | H | Me | 0 | NA | 2.3 | 6.9 | <1 |
NA, not available.
↵a Solubility, log D7.4 HPLC and pKa were measured as described previously (Boström et al., 2012).
↵b 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.