Table 4.
Cytotoxicity (in THLE-2 and PBMC cell lines), PAMPA-BBB, solubility and microsomal stability values of selected compounds.
 | ||||||||
|---|---|---|---|---|---|---|---|---|
| Compound | R | Cytotoxicity LC50 (μM) | pampa-BBB | Solubility[a] (μM) | Microsomal stability[b] | |||
| PBMC | THLE-2 | Human | Mouse | Rat | ||||
| 12 |  |
>20 | >100 | CNS− | 59 | 88.8 | 80.5 | 85.1 |
| 21 |  |
>20 | >100 | CNS− | >100 | 30.2 | 39.5 | 19.3 |
| 22 |  |
>20 | >100 | CNS− | 34 | 72.7 | 63.9 | 63.9 |
| 25 |  |
ND | >100 | CNS+ | 81.5 | 40 | 73 | 84 |
a
Solubility in a 1% DMSO : 99% PBS buffer solution.
b
Percentage of remaining compound after 60 min of incubation with human, mice and rat microsomes in the presence of NADPH at 37 °C. Metabolism of testosterone was used as a positive control. See Experimental Section for details.