TABLE 1

Physicochemical properties of compounds 1–9 and percentage of dihydrodiol metabolites formed in incubations with HLMs

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CompoundR1R2R3nSolubilityaLog DapKaaAverage % Diol in HLMs (Replicate 1, Replicate 2)b
µM
1MeOMeH0113.06.10 (0, 0)
2HHH01062.16.61.1 (1.2, 0.9)
3MeOHH0632.26.61.6 (1.6, 1.7)
4HHMe18582.38.415 (15, 15)
5MeOHMe1NA2.08.216 (16, 16)
6HMeMe18048.591 (89, 92)
7MeOMeMe1704.18.089 (88, 89)
8MeOHH1NA1.3NA2.7 (2.7, 2.8)
9MeOHMe0NA2.36.9<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.