Table 1. Preliminary SAR around Compound 6: Methyl-Walk, Antiviral, and FASN Inhibitory Activities.
compd | R1 | R2 | R3 | R4 | hFASNa (IC50, μM) | rFASNb (IC50, μM) | HCVc (EC50, μM) | CC50d (IC50, μM) | SIe |
---|---|---|---|---|---|---|---|---|---|
6 | Me | H | H | H | 0.107 | 1.72 | 0.175 | >20 | >114 |
7 | H | H | H | H | 0.130 | 2.95 | 0.550 | >3.0 | >5.0 |
8 | H | Me | H | H | >50 | >50 | >10 | >10 | N/A |
9 | H | H | Me | H | 0.060 | 0.635 | 0.150 | 8.6 | 57 |
10 | H | H | H | Me | >50 | >50 | >10 | 1.9 | <0.19 |
Biochemical inhibition of human FASN.
Biochemical inhibition of rat FASN.
Inhibition of HCV RNA in the replicon system. Telaprevir was used as a positive control.
Inhibition of cell viability.
SI = EC50/CC50; n ≥ 2, and CV ≤ 50%.