Table 7.
Physicochemical Parameters of 13a1 and 13c1–4
| compd | aqueous solubility (μg/mL)a |
log Pc | LEd | LLEe | LELPf | |||
|---|---|---|---|---|---|---|---|---|
| pH 7.4 | pH 7.0 | pH 2.0 | FaSSIFb | |||||
| 13a1 | 2.54 | 8.26 | 192 | 10.0 | 3.73 | 0.30 | 4.63 | 12.4 |
| 13c1 | 5.68 | 10.3 | 174 | 8.42 | 2.67 | 0.31 | 5.99 | 8.60 |
| 13c2 | 6.59 | 13.3 | 198 | 32.5 | 3.09 | 0.32 | 5.61 | 9.64 |
| 13c3 | <1 | 1.37 | 164 | 23.6 | 2.85 | 0.31 | 5.89 | 9.08 |
| 13c4 | 3.28 | 14.6 | 223 | 8.57 | 3.07 | 0.34 | 5.48 | 8.95 |
| 3 | ≪1 | 0.05 | 190 | 1.24 | 4.46 | 0.31 | 4.39 | 14.2 |
| ETV | <1 | <1 | 127 | 13.2 | 4.19 | 0.40 | 4.10 | 10.4 |
a
Measured by HPLC.
b
Fasted state simulated intestinal fluid.
c
Predicted by the software of ACS/Lab 6.0.
d
Calculated by the formula −ΔG/HA (non-hydrogen atom), in which normalizing binding energy ΔG = −RT ln Kd, presuming Kd ≈ EC50(IIIB).
e
Calculated by the formula pEC50 −log P.
f
Calculated by the formula log P/LE.