Table 2. Replacement of distal aromatic ring in BRD2108 with sp3-rich system preserves in vitro antiparasitic potency SAR of distal phenyl ring and aniline moiety with EC90 values.
Distal heteroaromatic compounds lost potency but aliphatic compounds maintained potency and show diversity at distal position. p-tolyl and methoxy anilines had the best potency but aliphatic and smaller substituents lost potency. Antiparasitic potency values provided (Tg EC50, Tg EC90) are an average of n = 2-3 experiments unless otherwise noted; ± indicates standard deviation. Compounds for which standard deviation is not provided were tested in only 1 experiment or exceeded a 10-μM EC90.
| |||
|---|---|---|---|
| ID | R1 | R2 | EC90 (μM) |
| BRD2108 |
|
|
0.46 ± 0.05 |
| mCMY096 |
|
|
4.88 |
| mCMY095 |
|
|
3.87 |
| mCMY173 |
|
|
>10 |
| mCMY174 |
|
|
4.17 |
| mCNV579 |
|
|
0.96 ± 0.06 |
| mCMY049 |
|
|
9.69 |
| kCMY093 |
|
|
>10 |
| kCMY175 |
|
|
3.63 ± 0.13 |
| mCMY176 |
|
|
>10 |
| mCMY233 |
|
|
>10 |
| mCMY230 |
|
|
0.71 ± 0.22 |
| mCMY177 |
|
|
5.60 |
| mCMY232 |
|
|
>10 |
| kCMY240 |
|
|
4.82 ± 0.13 |
| mCMY295 |
|
|
1.26 ± 0.08 |
| mCMY369 |
|
|
5.42 |
| mCMY413 |
|
|
4.63 ± 0.08 |
| mCMY370 |
|
|
>10 |
| mCMY373 |
|
|
4.78 |
| mCMY412 |
|
|
1.81 ± 0.41 |
| mCMY415 |
|
|
1.21 ± 0.09 |
| mCMY416 |
|
|
0.38 ± 0.02 |
| mCMZ070 |
|
|
3.09 ± 0.19 |
| mCMY544 |
|
|
3.07 ± 0.33 |
| mCMY546 |
|
|
0.46 ± 0.04 |
| mCMY835 |
|
|
3.89 ± 0.32 |
| mCMZ157 |
|
|
2.10 ± 1.10 |
| mCMZ557 |
|
|
0.52 ± 0.06 |
| mCMZ235 |
|
|
4.88 ± 0.73 |