Table 21.
SAR overview of advanced c-KIT inhibitors.
| Compd. | Cell IC50 (nM) |
hHEP [µL/min/106 cells] | CACO-2 [106 cm/s] (Efflux) |
FaSSiF [µg/mL] |
hERG [%inh] at 10 µM |
LogD | pKa |
|---|---|---|---|---|---|---|---|
| 135a | 48 | 18 | 12 (0.9) | 2 | 1% | 3.8 | - |
| 136a | 78 | 8 | 9.5 (0.7) | 4 | - | 4.0 | - |
| 136b | 46 | 4 | 6.4 (0.8) | - | - | 3.0 | - |
| 135b | 93 | 16 | 3.1 (4.7) | 16 | −15% | 4.4 | 6.9 |
| 135c | 61 | <4 | 5.7 (57) | 97 | −59% | 1.9 | 9.5 |
| 135d | 43 | - | - | - | −86% | 2.5 | nd |
| 135e | 70 | 18 | 12 (5.4) | - | −78% | 2.9 | 9.1 |
| 135f | 75 | 9 | 21 (5.0) | 13 | −23% | 3.0 | - |
| 135g | 76 | <4 | 7.6 (18) | 10 | −8% | 2.8 | 5.8 |
| 135h | 56 | 10 | 9.5 (15) | 16 | −19% | 1.5 | 7.3 |
| 135i | 73 | 10 | 1.8 (1.3) | 2 | −4% | 4.3 | 8.3 |
| 137 | 54 | 6 | 7.6 (7.5) | 10 | −7% | 3.2 | 6.3 |
| 135j | 59 | 21 | 5.7 (14) | 374 | −86% | 2.6 | 9.7 |