Table 3.
In silico predicted properties of the six FXR antagonists.
| Compd. | MWa | donorHBb | accptHBc | #rotord | QPlogSe | QPlogPo/wf | QPPCacog | Rule of fiveh | Rule of threei |
|---|---|---|---|---|---|---|---|---|---|
| 1a | 468.67 | 2.0 | 5.7 | 7 | −6.60 | 5.52 | 142.21 | 1 | 1 |
| 2a | 330.42 | 2.0 | 4.75 | 3 | −4.23 | 3.03 | 82.62 | 0 | 0 |
| 3a | 254.32 | 1.0 | 2.75 | 7 | −4.27 | 3.92 | 1315.91 | 0 | 0 |
| 3c | 252.31 | 1.0 | 2.75 | 6 | −4.33 | 3.59 | 1160.27 | 0 | 0 |
| 3d | 164.16 | 2.0 | 2.75 | 4 | −1.55 | 1.38 | 68.09 | 0 | 0 |
| 3e | 166.17 | 1.0 | 2.75 | 3 | −2.27 | 2.46 | 1083.37 | 0 | 0 |
| 6-ECDCA | 420.63 | 3.0 | 5.40 | 7 | −5.36 | 4.28 | 48.73 | 0 | 0 |
The recommended ranges by QikProp are as follows:
a
Molecular weight, 130.0–725.0.
b
Number of hydrogen bond donors, 0.0–6.0.
c
Number of hydrogen bond acceptors, 2.0–20.0.
d
Number of non-trivial rotatable bonds, 0–15.
e
Predicted aqueous solubility, −6.5–0.5.
f
Predicted octanol/water partition coefficient, −2.0–6.5.
g
Predicted apparent Caco-2 cell permeability in nm/sec, <25 poor, >500 great.
h
Number of violations of Lipinski's rule of five, maximum is 4.
i
Number of violations of Jorgensen's rule of three, maximum is 3.