Table 6. Cytochrome P450 (CYP) Inhibition Data for the Second-Generation NS5B Inhibitorsa.
IC50 (μM) (substrate probe) |
||||||
---|---|---|---|---|---|---|
Cmpd | series | CYP2C9 (diclofenac) | CYP2C19 (mephenytoin) | CYP3A4 (atorvastatin) | CYP3A4 (midazolam) | CYP3A4 (nifedipine) |
1 | N-benzyl | 4.9 | 18 | 7.1 | >33 | 28 |
31 | heteroaryl | 2.7 | 1.2 | 8.9 | >33 | >33 |
33 | 1.5 | 23 | 2.0 | >33 | >33 | |
47 | N-phenyl | 2.6 | 7.4 | 4.2 | >33 | 8.1 |
49 | 22 | >33 | >33 | >33 | >33 |
Experimental details are provided in the Supporting Information.