Table 3.
Anti‐tuberculosis activity of analogues with side chain modifications.[a]
|
| |||||
|---|---|---|---|---|---|
|
Compound |
R1 |
MIC90 (μM) |
|||
|
Mtb WT |
CFZ Resistant Mutant |
PA824 Resistant Mutant |
BDQ Resistant Mutant |
||
|
5 |
|
>256 |
>256 |
>256 |
>256 |
|
6j |
|
3.6 |
60 |
1.4 |
6.6 |
|
6k |
|
24 |
18 |
29 |
33 |
|
6l |
|
10 |
7.1 |
4.8 |
19 |
|
6m |
|
10 |
6.7 |
4.8 |
7.0 |
|
6n |
|
5.7 |
5.7 |
17 |
9.0 |
|
6o |
|
28 |
39 |
69 |
88 |
|
6p |
|
11 |
6.9 |
8.4 |
9.9 |
|
6q |
|
14 |
9.9 |
18 |
13 |
|
6r |
|
29 |
68 |
138 |
83 |
|
6s |
|
>256 |
>256 |
>256 |
>256 |
|
6t |
|
47 |
198 |
42 |
68 |
|
6u |
|
9.3 |
12 |
>512 |
14 |
|
6v |
|
34 |
25 |
44 |
21 |
|
6w |
|
55 |
73 |
69 |
42 |
|
6x |
|
113 |
225 |
>256 |
243 |
|
6y |
|
>256 |
>256 |
>256 |
>256 |
|
6z |
|
70 |
55 |
74 |
46 |
|
7z |
|
>256 |
>256 |
>256 |
>256 |
|
13 |
|
2.2 |
5.3 |
4.8 |
3.6 |
[a]MIC90 were determined by incubating Mtb cultures with the compounds (11‐point, 2‐fold dilution). On day 7, OD600 values were measured, and MIC90 values are reported in micromolar final concentration and were determined in biological triplicates. WT=wild type Mtb mc26206 strain. Mutant strains are based on the mc26206 strain. PA824 was used as the positive control (MIC90 0.53 μM) and CFZ (MIC90 0.39 μM).