Table 2. Effect of Pyridine Substitution on CYP11B2 and B1 Inhibition and LLE.
Cpd | R | hCYP11B2a (IC50, nM) | hCYP11B1a (IC50, nM) | LLEb |
---|---|---|---|---|
7 | F | 558 | >10000 | 3.86 |
8 | CF3 | 486 | >10000 | 3.18 |
9 | CO2CH3 | 58 | 2198 | 5.19 |
10 | C(O)NHCH3 | >8333 | >8333 | <3.68 |
11 | C(O)N(CH3)2 | >8333 | >8333 | <3.47 |
12 | SO2CH3 | >8333 | >8333 | <3.36 |
13 | SO2Ph | 40 | 1501 | 4.10 |
14 | C(CH3)2OH | 283 | >8333 | 4.38 |
15 | C(CH3)2OCH3 | 19 | 219 | 5.14 |
16 | C(CH3)2 CO2CH3 | 19 | 317 | 4.76 |
17 | 5 | 407 | 5.20 |
IC50s calculated from n ≥ 2, see Supporting Information for details.
Ligand lipophilic efficiency; LLE = pIC50 – aLogP98.