Table 3.
Characterization of conformationally restricted analogs.
| CMPD No. |
Structure | ALDH IC50a (μM) or % Control at 20 μM |
ADME Characterization | PEO1 Cell ALDEFLUORe (% inhib. @ 1 μM) |
||||
|---|---|---|---|---|---|---|---|---|
| 1A1 | 1A2 | 1A3 | MLMb t1/2 (min) |
Aq. Solc (μM) |
cLogPd | |||
| 36 |  |
1.0 ±0.1 | 0.17 ±0.02 | 0.15 ±0.05 | 5 | 38 | 3.7 | 54 ±3 |
| 38 |  |
0.206 ±0.06 | 0.4 ±0.1 | 0.69 ±0.08 | 8 | 3.9 | 2 ±2 | |
| 40 |  |
0.8 ±0.1 | 0.27 ±0.01 | 0.24 ±0.01 | 4.2 | 11 ±1 | ||
a
Values are expressed as mean ± SEM (n=3).
b
Half-life in mouse liver micorosomes.
c
Thermodynamic aqueous solubility (performed by Analiza Inc. using quantitative nitrogen detection (www.analiza.com)).
d
Calculated log P.
e
Mean ± SD as determined by flow cytometry (N=3).