Table 3.
PK and SPR analysis of prototype 7 and select analogs.
| Pharmacokinetic Parameters | In Vitro | In Vivo | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Compound Number | Structure | CLogP* | Solubility In PBS (mg/mL) | Microsomal Half Life (min) | CMax (ng/ml) | tmax | Vz (L/kg) | AUC0-t (ng/ml × hr) | CL (L/hr/kg) |
t1/2λ (hr) |
| 7 |  |
2.67 | 0.45 | 6.72 | 18,986 | 15 min | 10.9 | 12,488 | 3.87 | 1.96 |
| 42 |  |
2.57 | 1.52 | 8.53 | 10,887 | 15 min | 34 | 13,032 | 3.73 | 6.31 |
| 53 |  |
3.08 | 0.028 | >60 | 707 | 15 min | 108.9 | 2841 | 16.99 | 4.44 |
| 61 |  |
2.96 | 1.16 | 14 | 6,830 | 15 min | 32 | 12,871 | 3.71 | 5.97 |
| 60 |  |
2.71 | 0.045 | 30.18 | 1,982 | 15 min | 69.3 | 5,890 | 8.22 | 5.84 |
*
The consensus LogP (CLogP) values were obtained using the SwissADME website and tools.47