Table 4.
Calculated ADMET descriptors related to absorption and distribution properties as referred to the N(1)-benzotriazolyl-containing benzimidazoles 118, 120, 126, 157, and 158 (in green), the N(2)-benzotriazolyl-based 141, 148 (in yellow), the (pre)clinical (in gray) and clinical (in cyan) candidates TMC353121, BMS-433771, JNJ-2408068 and JNJ-53718678, GS-5806, and RV521, respectively.
| Comp. | HIA (%) a | Vd (L/kg) b | %PPB c | LogKaHSA d | %F (oral) e |
|---|---|---|---|---|---|
| 118 | 100 | 1.2 | 98.15 | 5.20 | 99.2 |
| 120 | 100 | 3.0 | 94.00 | 4.98 | 99.3 |
| 126 | 100 | 1.4 | 98.98 | 5.32 | 99.1 |
| 157 | 100 | 1.2 | 92.41 | 4.75 | 99.4 |
| 158 | 100 | 1.3 | 99.27 | 5.17 | 99.1 |
| 141 | 100 | 1.5 | 98.14 | 4.56 | 99.1 |
| 148 | 100 | 1.3 | 98.11 | 4.96 | 99.2 |
| BMS-433771 | 100 | 1.2 | 94.63 | 4.04 | 99.4 |
| TMC-353121 | 3 | 1.6 | 77.52 | 2.93 | 1.4 |
| JNJ-2408068 | 71 | 1.2 | 87.61 | 3.39 | 47.1 |
| JNJ-53718678 | 100 | 1.0 | 99.05 | 5.42 | 21.0 |
| GS-5806 | 93 | 0.7 | 87.94 | 4.95 | 73.5 |
| RV521 | 100 | 1.1 | 90.76 | 3.95 | 69.0 |
a HIA represents the human intestinal absorption, expressed as percentage of the molecule able to pass through the intestinal membrane; b prediction of Volume of Distribution (Vd) of the compound in the body; c plasmatic protein binding event; d ligand affinity toward human serum albumin; and e oral bioavailability as a percentage.