Table 3. Effect of Benzimidazole Substitution on CYP11B2 and B1 Inhibition and LLE.
| compd | R | CYP11B2a (IC50, nM) | CYP11B1a (IC50, nM) | B1/B2b | LLEc |
|---|---|---|---|---|---|
| 11 | H | 49 | >8333 | >170 | 4.49 |
| 12 | 4-F | 219 | >8333 | >38 | 3.64 |
| 13 | 5-F | 28 | 3984 | 142 | 4.53 |
| 5 | 6-F | 3.8 | 400 | 105 | 5.38 |
| 14 | 7-F | 107 | >10000 | >93 | 3.95 |
| 15 | 5-CF3 | >10000 | >10000 | n.d. | n.d. |
| 16 | 5-OCH3 | >1000 | >10000 | n.d. | n.d. |
| 17 | 5-CN | 1768 | >10000 | >6 | 3.06 |
| 18 | 5-SO2CH3 | >1000 | >10000 | n.d. | n.d. |
| 19 | 6-Cl | 2.2 | 477 | 215 | 5.18 |
| 20 | 6-CF3 | 254 | 1831 | 7 | 2.84 |
| 21 | 6-CN | 1.2 | 374 | 309 | 6.22 |
| 22 | 6-OCH3 | 24 | 1980 | 83 | 4.82 |
| 23 | 5,6-di-F | 2.1 | 370 | 176 | 5.45 |
| 24 | 5-F-6-Cl | 0.4 | 334 | 835 | 5.71 |
| 25 | 5-F-6-CN | 0.6 | 117 | 195 | 6.32 |
a
Assay details reported in Supporting Information.
b
Ratio of hCYP11B1 IC50/hCYP11B2 IC50.
c
Ligand lipophilic efficiency; LLE = pIC50 – a Log P98.