Table 2.
Focused set of four deuterated analogs designed around ND-11176 (2) and screened against M. tuberculosis H37Rv in two types of media (GAS and 7H12), in LORA conditions and for toxicity against Vero cells. Units in nanomolar (nM).
| MIC (nM) | IC50 (nM) | ||||||
|---|---|---|---|---|---|---|---|
|
|
|
|
|
|
|
||
| Cmpd | MW | ClogP* | Structure | GAS MIC | 7H12 MIC | LORA MIC | Vero |
|
| |||||||
| 30 | 353.37 | 4.48 |
|
9.1 ± 5.8 | 3.8 ± 1.3 | >10,000 | >50,000 |
| 52 | 352.37 | 4.48 |
|
7.4 ± 2.8 | 3.9 ± 1.6 | >10,000 | >50,000 |
| 55 | 355.39 | 4.48 |
|
9.6 ± 2.6 | 4.9 ± 1.3 | >10,000 | >50,000 |
| 57 | 357.40 | 4.48 |
|
5.7 ± 1.2 | 6.7 ± 0.9 | >10,000 | >50,000 |
| 2 | 347.34 | 4.48 |
|
11.3 ± 2.5 | 7.1 ± 2.5 | >10,000 | >50,000 |
| Q203 | 557.01 | 7.62 |
|
0.9 ± 0.4 | 3.6 ± 0.5 | >5,000 | >50,000 |
*
ClogP was calculated from PerkinElmer Chemdraw® Professional version 16.0.1.4.