Table 9.
Compound number |
Substituent X | MIC (µM) | Microsomal stability after 1 h (ratio remaining) |
In vivo efficacy (% relative to PA-824, (5)) |
||
---|---|---|---|---|---|---|
MABA | LORA | Human | Mouse | |||
5 | 0.5 | 2.6 | 0.82 | 0.94 | 100 | |
106 | 0.035 | 1.3 | 0.97 | 0.96 | >25000 | |
123 | 0.06 | 0.58 | 0.86 | 0.81 | 1200 | |
124 | 0.05 | 0.61 | 0.87 | 0.67 | 4100 | |
125 | 0.075 | 3.3 | 0.99 | 0.74 | 34 | |
126 | 0.035 | 1.3 | 0.97 | 0.81 | 4300 |
Data from [34].
LORA: Low-oxygen recovery assay where hypoxically adapted cells are incubated with compound under anaerobic conditions followed by an aerobic recovery to measure luminescence as a surrogate readout of the number of cells prior to recovery; MABA: Microplate Alamar blue assay, aerobic MIC as determined by Alamar Blue-based readout of redox activity in cells; MIC: Minimum inhibitory concentration.