Table 1. SAR Studies of the Salicylate Region of 1.
| compound | R1 | R2 | MIC (μM) | TC50 (μM) |
|---|---|---|---|---|
| rifampicin | 0.0040 | >50 | ||
| 1(NTZ) | AcO– | H | 14 ± 0 | >20 |
| 2 | HO– | H | 20 ± 0 | >20 |
| 3 | OGlucoron | H | >20 | >50 |
| 4 | H– | H | >20 | 19 |
| 5 | H2N– | H | >20 | 31 |
| 6 | MeHN– | H | >20 | 15 |
| 7 | AcHN– | H | >20 | ND |
| 8 | Et(Me)2CCO2– | H | 1.4 ± 0.070 | 6.2 |
| 9 | Et(Me)2CCOHN– | H | 17 ± 4.9 | 4.1 |
| 10 | t-BuOCOHN– | H | 17 ± 4.2 | 6.6 |
| 11 | HO– | 5-F | >20 | ND |
| 12 | HO– | 5-Me | >20 | 12 |
| 13 | HO– | 3-Me | >20 | 12 |
| 14 | Et(Me)2CCO2– | 4-(N-morpholinyl) | >20 | 12 |
| 15 | HO– | 5-OH | >20 | 13 |
| 16 | HO2C– | H | >20 | >50 |
| 17 | MeO– | H | >20 | ND |
| 18 | 3-(Et(Me)2CCOHN−) | N/A | 1.4 ± 0.60 | 0.9 |
| 19 | H | N/A | 2.4 ± 0.0071 | 20 |
| 20 | 4-OMe | N/A | 5.6 ± 4.2 | 11 |
| 21 | 5-OMe– | N/A | 5.5 ± 2.1 | 4.3 |
| 22 | 3-iPrO– | N/A | 16 ± 6.4 | 8.9 |
| 23 | 3-(Et(Me)2CCO2−) | N/A | 12 ± 1.0 | 21 |
| 24 | 3-OMe | N/A | >20 | 37 |
| 25 | 5-(N-morpholinyl) | N/A | >20 | 11 |
a
Compounds were tested for activity against M. tuberculosis. MIC is the minimum concentration required to inhibit the growth of M. tuberculosis in liquid culture. MICs of active compounds are the average ± standard deviation of two independent experiments.
b
Toxic concentration (TC50) is the concentration required to inhibit growth of Vero cells by 50%. ND = not determined. Note that compounds 1 and 2 were tested at a maximum concentration of 20 μM, all other compounds were tested at a maximum concentration of 50 μM.