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. 2015 Apr 7;6(5):573–578. doi: 10.1021/acsmedchemlett.5b00054

Table 4. Effect of Pyridine Substitution on CYP11B2 and B1 Inhibition and LLE.

graphic file with name ml-2015-000548_0005.jpg

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
a

Assay details reported in Supporting Information.

b

Ratio of hCYP11B1 IC50/hCYP11B2 IC50.

c

Ligand lipophilic efficiency; LLE = pIC50a Log P98.