TABLE 1.
Inhibition of HRV 2A and 3C proteases by homophthalimidesa
| Compound | Structure
|
IC50 (μM)
|
|||
|---|---|---|---|---|---|
| R1 | R2 | HRV2 2A | HRV14 2A | HRV14 3Cb | |
| LY046601 | -CH3 | -CH2COPh(p-F) | 21.8 | 56.2 | 41.1 |
| LY343813 | -(CH2)3CO2Et | -H | >200 | 18.2 | >200 |
| LY343814 | -n-Bu | -COMe | >200 | 19.7 | >200 |
| LY344453 | -(CH2)3SMe | -H | >200 | 98.3 | >200 |
| LY353348 | -(CH2)2SMe | -CH2COPh | 8.4 | >100 | >200 |
| LY353349 | -(CH2)2SO2Me | -CH2COPh | 3.1 | 44.6 | 22.1 |
| LY353350 | -(CH2)3CO2Et | -COMe | >200 | 26.5 | >200 |
| LY353352 | -(CH2)2CO2Et | -CH2COPh | 3.9 | 63.3 | 55.4 |
| LY353353 | -(CH2)3SMe | -CH2COPh | 23.1 | 56.0 | 130.6 |
| LY353354 | -(CH2)3SO2Me | -CH2COPh | 31.3 | NDc | 25.0 |
| LY355451 | -(CH2)3CO2Et | -CH2CO-proline | >100 | >100 | 56.9 |
a
Inhibition assays were carried out as described in Materials and Methods. Control sample contained only the inhibitor solvent (dimethyl sulfoxide) and counted as no inhibition. Experiments were run in duplicate, and data are averages with variations of less than 5%. Me, methyl; Et, ethyl; Ph, benzylic.
b
Data from reference 8.
c
ND, not done.