Table 1.
Luciferase-based HCV 1b replicon activity of ProTides 31a-k
 | |||||||
|---|---|---|---|---|---|---|---|
| Cmpd | R | Amino acid | EC50 (µM)a |
EC90 (µM)a |
CC50 (µM)a |
SI50 | clogP |
| 2’-C-Me-uridine | - | - | 6.31 | 55.3 | >100 | >15.8 | −1.69 |
| 31a |  |
L-glutamic acid | 1.52 | 5.6 | >20 | >13 | −1.28 |
| 31b |  |
L-glutamic acid | 0.08 | 0.21 | >20 | >250 | 2.69 |
| 31c |  |
L-serine | 0.18 | 0.6 | >20 | >111 | 0.65 |
| 31d |  |
L-serine | 0.03 | 0.14 | 5.89 | 196 | 2.77 |
| 31e |  |
L-serine | < 0.06 | 0.13 | 8 | >127 | 2.64 |
| 31f |  |
L-serine | 0.51 | 1.69 | >20 | >39 | −0.12 |
| 31g |  |
L-serine | 0.10 | 0.86 | 6.79 | 68 | 1.99 |
| 31h |  |
L-serine | 0.08 | 0.56 | 7.51 | 94 | 1.87 |
| 31i |  |
L-threonine | 0.29 | 1.39 | >20 | >69 | 2.18 |
| 31j |  |
L-threonine | 0.47 | 1.83 | 11.46 | 24 | 2.94 |
| 31k |  |
L-tyrosine | 0.40 | 1.47 | >20 | >50 | 2.82 |
| IFNα-2b | - | - | 0.15 | 0.48 | >10 | >67 | |
| Sofosbuvir | See Figure 1 | L-alanine | 0.07 | 0.30 | >5.00 | >71 | |
a
Results are from a single assay generated from quadruplicate assay wells at each concentration