Table 1.
IC50 values (μM) of kinase inhibition, A431 cytotoxicity and inhibition of the CAM assay.
| Compd # | R | EGFR Inhibitiona | VEGFR-1 Inhibitiona | VEGFR-2 Inhibitiona | PDGFR-β Inhibitiona | A431 Cytotoxicitya | CAM Angiogenesis Inhibitiona |
|---|---|---|---|---|---|---|---|
| 19 (12) | 3′-Br | >200 (0.3 ±0.042) | 129.4 ± 30.1 (45.1 ±8.9) | 112.3 ± 18.1 (>50) | 8.5 ± 2.4 (11.8 ±3.7) | >500 (28.6 ±8.2) | 1.93 ± 0.09 (19.5 ±5.1) |
| 20 (13) | 3′-ethynyl | >200 (>200) | 142.3 ± 23.5 (>200) | 49.4 ± 8.0 (>200) | >500 (100.4 ±22.1) | >500 (8.5 ±1.1) | 5.12 ± 0.46 (1.1 ±0.07) |
| 21 (14) | 3′-CF3 | >200 (>200) | >200 (>200) | 22.1 ± 4.1 (>200) | >500 (>500) | >500 (4.6 ±0.67) | 5.63 ± 0.67 (0.03 ±0.004) |
| 22 (15) | 3′-Br, 4′-F | >200 (22.8 ±4.7) | >200 (>200) | 25.2 ± 5.2 (132.1 ±16.7) | 192.4 ± 20.8 (>500) | >500 (6.8 ±0.71) | 2.14 ± 0.39 (5.9 ±0.7) |
| 23 (16) | 3′-CF3, 4′-F | >200 (122 ±30.1) | 164.3 ± 18.1 (>200) | 57.5 ± 7.1 (>200) | >500 (90.0 ±17.8) | >500 (9.8 ±1.0) | 19.6 ± 5.9 (0.12 ±0.12) |
| 24 | 2′-F, 4′-Cl | >200 | >200 | 40.5 ± 9.3 | >500 | 43.0 | 36.9 ± 3.2 |
| (17) | (1.32 ±0.09) | (>200) | (>200) | (>500) | (1.4 ±0.12) | (8.6 ±7.6) | |
| 25 (18) | 3′,4′-(C2H3N) | 56.1 ± 8.7 (>200) | 223.8 ± 41.3 (>200) | 31.6 ± 8.8 (24.9 ±4.1) | 104.2 ± 16.7 (77.4 ± 9.1) | 81.9 ± 10.1 (5.5 ± 1.4) | 20.1 ± 4.8 (50.6 ±18.8) |
| 7 | 0.2 ±0.04 | 12.6 ±2.9 | |||||
| 8 | 17.7 ±5.5 | ||||||
| 9 | 10.6 ±2.7 | 19.2 ±1.1 | 0.085 ±0.0031 | ||||
| 10 | 6.5 ±1.3 | ||||||
| 11 | 7.65 ±1.4 |
a
Values in parentheses are for the corresponding 2-amino compounds.16 All the values are means of three experiments; standard deviation follows the mean value.