TABLE 2

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

Embedded Image
CompoundR1R2R3nSolubilityaLog DapKabAverage % Diol in HLMs (Replicate 1, Replicate 2)c
µM
15MeMeMe12581.68.29.9 (10.0, 9.9)
16MeMeMe15860.49.31.5 (0, 3.1)
17Embedded ImageMeMe19500.88.22.3 (2.1, 2.5)
18MeMeMe26121.68.93.1 (3.0, 3.1)
19MeHMe26280.59.70.7 (0.7, 0.7)
20MeMeH25871.08.90 (0, 0)
  • a Solubility and logD7.4 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.