Table 4.
“Second series” analogs used for SAR validation. Inhibition parameters were determined from kinetic studies with DEN2V NS2B-NS3 and trypsin proteases. Compounds soluble in aqueous buffer were indicated with “S” and insoluble compounds indicated with “NS.” Relative solubilities (clogS, calculated with the OSIRIS program) were listed in parenthesis.
| Compound | Structure | Solubility (clogS*) |
DEN2V NS2B-NS3 | Trypsin | ||||
|---|---|---|---|---|---|---|---|---|
| Ki1 (µM) |
Ki2 (µM) |
Mechanism | Ki1 (µM) |
Ki2 (µM) |
Mechanism | |||
| 6A60 |  |
S (−3.9) | 7 ± 5 | 3 ± 1 | Mixed | - | - | No inhibition |
| 6A61 |  |
S (−3.6) | 72 ± 15 | 10 ± 2 | Mixed | - | - | No inhibition |
| 6A62 |  |
S (−4.2) | 508 ± 47 | - | Competitive | - | 5 ± 0.4 | Uncompetitive |
| 6A63 |  |
NS (−4.4) | ||||||
*
calculated log of the compound’s aqueous solubility (S), with units for S being mol l−1