Review Article
Synthesis and Structural Activity Relationship Study of Antitubercular Carboxamides
Table 6
SAR and MIC of tetrahydropyrazolopyrimidine carboxamides.
| Compounds | R1 | R2 | R3 | MIC (µM) | | Solubilityb (mM, pH 6.8) | PPB (%)c (h/m) |
| 65 | | | CF3 | 0.15 ± 0.04 | 6.3 | <4 | >99.0/99.0 |
| 66 | | | CF3 | 0.44 ± 0.1 | 4.4 | 9 | 96.1/95.8 |
| 67 | | | CF3 | 0.13 ± 0.06 | 5.5 | <4 | >99.0/99.0 |
| 68 | | | CF3 | 0.87 ± 0.18 | 4.8 | <4 | 98.2/98.4 |
| 69 | | | CF3 | 0.44 ± 0.04 | 4.1 | 6 | 98.1/98.5 |
| 70 | | | CF3 | 0.73 ± 0.1 | 5.1 | 9 | 97.3/97.6 |
| 71 | | | CF3 | 0.47 ± 0.15 | 5.1 | <4 | >99.0/99.0 |
| 72 | | | CF3 | 0.83 ± 0.24 | 4.9 | <4 | >99.0/99.0 |
| 73 | | | CHF2 | 0.60 ± 0.2 | 4.6 | 212 | 95.7/94.8 |
| 74 | | | CF3 | 52.2 ± 24.1 | 3.2 | 347 | 81.9/87.2 |
| 75 | | | CF3 | 3.7 ± 0.6 | 3.2 | 20 | 87.8/89.2 |
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: high throughput measured octanol/water partition coefficient, bsolubility: high throughput equilibrium solubility, cPPB: plasma protein binding measured by rapid equilibrium dialysis (RED) device.
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