Table 5. In Vitro ADME Properties of Representative Compoundsa.
| PPB
(%) |
microsomal
stability (% remaining at 2 h) |
plasma
stability (% remaining at 2 h) |
||||
|---|---|---|---|---|---|---|
| compound | human | mouse | human | mouse | human | mouse |
| pretomanid 2 | 97 ± 1.1 | 91 ± 1.3 | 97 ± 5.0 | 92 ± 2.7 | 96 ± 6.9 | 96 ± 1.9 |
| 17k | 78 ± 4.1 | 74 ± 3.4 | 8.5 ± 0.73 | ND | 96 ± 6.8 | ND |
| 26j | 79 ± 0.44 | 72 ± 1.3 | 98 ± 2.5 | ND | 95 ± 4.3 | ND |
| 34e | 96 ± 0.88 | 93 ± 0.26 | 96 ± 7.7 | 20 ± 4.0 | 93 ± 2.6 | >99 |
| 34g | >99 | >99 | 98 ± 2.6 | ND | 98 ± 2.1 | ND |
| 34j | >99 | >99 | >99 | 98 ± 1.9 | >99 | >99 |
| 34k | >99 | >99 | >99 | ND | >99 | ND |
| 34p | 97 ± 0.30 | 99 ± 0.02 | 37 ± 1.7 | ND | >99 | ND |
a
Values are presented as mean of three replicates ± SD. Microsomal stability control, verapamil at 30 min = 9% (human), 2% (mouse). Plasma stability control, eucatropine at 2 h = 28% (human), 29% (mouse). % bound of PPB control, sulfamethoxazole = 57% (human), 9% (mouse). ND, not determined.