Table 1. Activity of N-Sulfamoyl Pyrrole Carboxylate Derivatives against Clinically Relevant MBLs.
| pIC50 |
||||
|---|---|---|---|---|
| VIM-1 | NDM-1 | VIM-2 | IMP-1 | |
| CB2 | 7.142 | 7.543 | 8.543 | 6.043 |
| taniborbactam | 8.141 | 8.041 | 8.341 | 5.641 |
| 6a | 6.9 | 8.1 | 7.7 | 9.2 |
| 6b | 6.9 | 8.2 | 7.5 | 8.9 |
| 8 | 7.1 | 7.9 | 6.8 | 8.6 |
| 9 | 6.5 | 7.9 | 6.7 | 9 |
| 10 | 7.1 | 8.1 | 7.8 | 8.9 |
| 11 | 7.4 | 7.9 | 7.3 | 8.2 |
| 12 | 8.5 | 6.5 | 7.9 | 7.3 |
| 13 | 6.6 | 8.8 | 6.8 | >9.2 |
| 14 | 7.4 | 7.9 | 8.2 | 8.3 |
| AMRC272a,c | 6.122 | 4.522 | 6.422 | |
| AMRC276a,c | 6.822 | 4.222 | 7.422 | |
| AMRC364a,c | 5.622 | 4.422 | 5.722 | |
| AMRC439a,c | 6.422 | 4.322 | 6.322 | |
| SPCb | 6.021 | 7.721 | 6.621 | |
a
Determined using 100 μM nitrocefin.22
b
Determined by measuring hydrolysis of imipenem.21
c
Structure in Figure 1d. Assay details are given in the Supporting Information. Enzyme concentration: 100 pM (VIM-1), 20 pM (NDM-1), 20 pM (IMP-1), and 500 pM (VIM-2); the concentration of FC5 was 5 μM. Note: inhibition data are reported as pIC50 values (pIC50 = −log10IC50) and repeated in quadruplicate.