Table 1.
Fitness scores on ModB and ModC, MIC values and CPX MIC fold reduction from synergistic assays at 12.5 μg/mL for compounds 6 a, 6 b, 7 a, 7 b, 8 a–f, 9 a, 9 b, 10 a, 10 b, 11 a, 11 b, 12 a–c, 13 a and 13 b and reference compound 1.
|
Compd. |
R1/R4 |
Fitness scores |
SA‐1199 |
SA‐1199B |
||||
|---|---|---|---|---|---|---|---|---|
|
|
|
ModB |
ModC |
MIC [μg/mL] |
Fold reduction[a] |
MIC [μg/mL] |
Fold reduction[a] |
|
|
6 a |
|
|
1.9 |
1.5 |
50 |
–[b] |
50 |
4 |
|
6 b |
|
1.9 |
1.7 |
>50 |
–[b] |
>50 |
4 |
|
|
7 a |
|
|
2.0 |
1.8 |
NT c |
NT[c] |
NT[c] |
NT[c] |
|
7 b |
|
1.9 |
1.7 |
25 |
4 |
50 |
4 |
|
|
11 a |
|
1.5 |
1.0 |
>50 |
4 |
>50 |
4 |
|
|
11 b |
|
1.7 |
1.0 |
>50 |
–[b] |
>50 |
4 |
|
|
8 a |
|
|
2.1 |
1.8 |
25 |
2 |
25 |
16 |
|
8 b |
|
2.1 |
1.8 |
25 |
2 |
50 |
16 |
|
|
8 c |
|
ND[d] |
ND[d] |
>50 |
–[b] |
>50 |
16 |
|
|
8 d |
|
ND[d] |
ND[d] |
12.5 |
NT[c] |
12.5 |
NT[c] |
|
|
8 e |
|
ND[d] |
ND[d] |
>50 |
–[b] |
>50 |
4 |
|
|
8 f |
|
ND[d] |
ND[d] |
12.5 |
NT[c] |
12.5 |
NT[c] |
|
|
9 a |
|
|
2.0 |
1.7 |
25 |
–[b] |
25 |
2 |
|
9 b |
|
2.0 |
1.8 |
>50 |
4 |
50 |
2 |
|
|
10 a |
|
|
1.8 |
1.8 |
25 |
–[b] |
25 |
8 |
|
10 b |
|
1.8 |
1.8 |
50 |
2 |
50 |
4 |
|
|
12 a |
|
|
ND[d] |
ND[d] |
12.5 |
NT[c] |
12.5 |
NT[c] |
|
12 b |
|
ND[d] |
ND[d] |
>50 |
–[b] |
>50 |
8 |
|
|
12 c |
|
ND[d] |
ND[d] |
>50 |
–[b] |
>50 |
8 |
|
|
13 a |
|
|
ND[d] |
ND[d] |
>50 |
2 |
>50 |
8 |
|
13 b |
|
ND[d] |
ND[d] |
>50 |
2 |
>50 |
8 |
|
|
1 |
|
|
2.0 |
1.7 |
>50 |
–[b] |
>50 |
4 |
[a] CPX MIC fold reduction from synergistic assays with compounds tested at the single concentration of 12.5 μg/mL; [b] No CPX MIC reduction. [c] NT=Not tested. [d] ND=Fitness scores not evaluated since the new designed analogues possessed the same scaffold as 8 a and 8 b.