Table 4.
Compound# | MLMSa (%) |
HLMSb (%) |
CYP3A4 % INHc |
Solubilityd (µM) |
---|---|---|---|---|
morpholinyl compounds | ||||
MBX 2319 | 0 | 0 | 12 | 12 |
20f | 0 | 8 | 29 | 50 |
20r | 5 | 21 | 49 | 25 |
(2-methoxyethyl)piperazinyl compounds | ||||
19e | 0 | 0 | 18 | 50 |
21a | 3 | 0 | 14 | ≥ 100 |
21f | 17 | N.D. | 42 | ≥ 100 |
21g | 13 | 20 | 48 | ≥ 100 |
2,6-dimethylmorpholinyl compounds | ||||
22a | 19 | 53 | 0 | ≥ 100 |
22d | 66 | 59 | 0 | 100 |
22e | 72 | 76 | 59 | 12 |
22f | 0* | 37 | 61 | 50 |
22g | 0* | 90 | 66 | 12.5 |
22i | 49 | 100 | 90 | 25 |
22k | 90 | 90 | 9 | 100 |
MLMS, murine liver microsome stability, % remaining after 60 min at 37 °C in the presence of NADPH.
HLMS, human liver microsome stability, % remaining after 60 min at 37 °C in the presence of NADPH.
CYP3A4 INH, percent inhibition produced by 3 µM compound.
Solubility, maximum solubility in water as determined using a nephelometric assay32
NADPH independent consumption