Table 2. TSPO Affinity of Compounds 20–24 and Their Effects on Increase of Pregnenolone Production.
| cpd | R1 | R2 | R3 | R4 | Ki (nM) or inhibition (%)a | increase of pregnenolone production vs control (%)b |
|---|---|---|---|---|---|---|
| 20c | (CH2)5CH3 | (CH2)5CH3 | Cl | Cl | 5.8 ± 0.6 | 166 ± 12 |
| 21d | CH2CH3 | CH2C6H5 | Cl | Cl | 3.33 ± 0.3 | 171 ± 14 |
| 22c | (CH2)3CH3 | (CH2)3CH3 | Cl | Cl | 1.9 ± 0.2 | 147 ± 13 |
| 23d | (CH2)5CH3 | (CH2)5CH3 | F | Cl | 7.75 ± 1.55 | 135 ± 4 |
| 24c | (CH2)2CH3 | (CH2)2CH3 | CH3 | H | 5.50 ± 0.38 | 148 ± 12 |
| Ro5-4864 | 23 ± 3.1 | 41 ± 4 | ||||
| PK11195 | 9.3 ± 0.5 | 48 ± 5 |
a
The concentration of compounds that inhibited [3H]PK11195 binding in rat kidney mitochondrial membranes (IC50) by 50% was determined with six concentrations of the displacers, each performed in triplicate. Ki values represent the mean ± SEM of three determinations.
b
C6 glioma cells were incubated for 2 h at 37 °C in the presence of each compound. Pregnenolone was measured by radioimmunoassay. Values are the mean ± SEM of three determinations.
c
Data taken from Primofiore et al.59
d
Data taken from Da Settimo et al.60