Table 4. Effect of Pyridine Substitution on CYP11B2 and B1 Inhibition and LLE.
compd | R1 | R2 | R3 | R4 | CYP11B2a (IC50, nM) | CYP11B1a (IC50, nM) | B1/B2b | LLEc |
---|---|---|---|---|---|---|---|---|
23 | F | F | H | H | 2.1 | 370 | 176 | 5.45 |
26 | F | F | H | F | 4.7 | 435 | 93 | 5.01 |
27 | F | F | H | CN | 22.3 | 1552 | 70 | 4.54 |
28 | F | F | H | OCH3 | 0.4 | 250 | 606 | 6.12 |
29 | F | Cl | H | F | 0.8 | 251 | 296 | 5.20 |
30 | F | CN | H | F | 1.0 | 225 | 225 | 5.89 |
31 | F | F | H | C(CH3)2OH | 0.3 | 42 | 140 | 6.32 |
32 | H | F | H | C(CH3)2OH | 2.3 | 142 | 71 | 5.70 |
33 | F | F | CH3 | H | 10.2 | 723 | 71 | 4.28 |
34 | F | F | CF3 | H | 8.1 | 795 | 98 | 3.92 |
35 | F | F | CH3 | F | 0.5 | 258 | 553 | 5.38 |
36 | F | F | CH3 | CH3 | 0.2 | 17.7 | 74 | 5.50 |
37 | F | F | OCH3 | CH3 | 0.6 | 435 | 709 | 5.52 |
Assay details reported in Supporting Information.
Ratio of hCYP11B1 IC50/hCYP11B2 IC50.
Ligand lipophilic efficiency; LLE = pIC50 – a Log P98.