Table 3.
Properties of the Selected Lead Compounds
| Cmpd. | Plasma | Liver | Liver/Plasma Ratioc | CMax/EC50d | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TMax (h) | CMax (μM) | T1/2 (h) |
AUC24h (h·μM) | bAUC∞ (h·μM) | TMax (h) | CMax (μM) | T1/2 (h) |
AUC24h (h·μM) | bAUC∞ (h·μM) | |||
| 1 a | 0.25 | 3.2 | 2.0 | 9.8 | 9.8 | 0.083 | 87 | 2.0 | 262.3 | 262.5 | 26.8 | 3.6 |
| 2 | 0.083 | 5.3 | 6.7 | 27.6 | 29.9 | 0.083 | 54.7 | 8.5 | 431.1 | 497.0 | 15.6 | 3.2 |
| 3 | 0.083 | 3.5 | 4.7 | 7.3 | 7.5 | 0.083 | 80.43 | 4.8 | 145.1 | 149.0 | 19.9 | 35.0 |
| 7 | 0.25 | 6.9 | 2.6 | 27.2 | 27.2 | 0.25 | 52.6 | 4.6 | 289.1 | 296.5 | 10.6 | 5.3 |
| 9 | 0.083 | 1.8 | 12.0 | 2.9 | 3.6 | 24 | 161.12 | ND | 3536.8 | ND | 1231.0 | 5.4 |
| 12 | 0.083 | 6.9 | 15.3 | 8.0 | 9.8 | 4 | 95.98 | ND | 1908.4 | ND | 239.9 | 3.4 |
a 50 mg/kg dosage. AUC24, AUC∞’ and CMax have been reduced to one-fifth of their measured value for comparison.
b Extrapolated total exposure from a single dose.
c Ratio of AUC24.
d 50% viral inhibition (EC50), see Table 1.
Abbreviations: AUC∞, area under the curve extrapolated from time 0 to infinity (total compound exposure); AUC24h, area under the curve (compound exposure) from time 0 to 24h; CMax, maximum concentration; Cmpd, compound; ND, not determined; TMax time to reach Cmax; T1/2, half-life.