Table 1.
Structures of the target compounds 1a-zh and their inhibitory effects against RAF1 and V600E-B-RAF kinases. The inhibition percentage results are expressed as means of duplicate assays ± SEM
| Compound no. | Structure | One-dose (1 µM) results against RAF1 (% inhibition) | One-dose (1 µM) results against V600E-B-RAF (% inhibition) | IC50 value (nM) against RAF1 | IC50 value (nM) against V600E-B-RAF |
|---|---|---|---|---|---|
| 1a |  |
54.04% ± 5.07% | 67.62% ± 3.61% | ND | ND |
| 1b |  |
63.81% ± 2.51% | 73.06 ± 1.72% | ND | 245 nM |
| 1c |  |
59.53% ± 2.25% | 52.03% ± 3.61% | ND | ND |
| 1d |  |
63.44% ± 1.62% | 69.37% ± 0.05% | ND | ND |
| 1e |  |
62.63% ± 0.34% | 90.43% ± 0.72% | ND | 144 nM |
| 1f |  |
71.39% ± 1.32% | 90.99% ± 0.56% | ND | 83.8 nM |
| 1g |  |
13.99% ± 2.28% | 38.64% ± 0.21% | ND | ND |
| 1h |  |
38.67% ± 5.01% | 77.90% ± 0.11% | ND | 191 nM |
| 1i |  |
55.46% ± 1.61% | 85.45% ± 0.42% | ND | 142 nM |
| 1j |  |
69.84% ± 0.52% | 91.40% ± 0.48% | ND | 78.2 nM |
| 1k |  |
66.14% ± 2.60% | −5.63 ± 3.11% | ND | ND |
| 1l |  |
13.09% ± 0.12% | 40.59% ± 1.72% | ND | ND |
| 1m |  |
75.89% ± 1.43% | 80.25% ± 0.61% | ND | 82.6 nM |
| 1n |  |
75.69% ± 0.67% | 84.82% ± 0.42% | ND | 120 nM |
| 1o |  |
32.50% ± 1.91% | 52.76% ± 3.66% | ND | ND |
| 1p |  |
60.68% ± 0.95% | 69.65% ± 0.40% | ND | ND |
| 1q |  |
19.33% ± 2.37% | 23.59% ± 1.99% | ND | ND |
| 1r |  |
97.45% ± 0.10% | 97.66% ± 0.16% | 45.6 nM | 11.2 nM |
| 1s |  |
97.28% ± 0.08% | 99.54% ± 0.23% | 49.7 nM | 18.4 nM |
| 1t |  |
67.56% ± 4.79% | 87.74% ± 0.38% | ND | 194 nM |
| 1u |  |
74.00% ± 0.64% | 95.03% ± 0.66% | ND | 45.1 nM |
| 1v |  |
59.25% ± 2.53% | 90.82% ± 0.25% | ND | 100 nM |
| 1w |  |
56.61% ± 2.15% | 83.65% ± 0.47% | ND | 121 nM |
| 1x |  |
32.14% ± 0.08% | 56.21% ± 0.10% | ND | ND |
| 1y |  |
57.47% ± 0.47% | 63.23% ± 0.93% | ND | ND |
| 1z |  |
32.12% ± 2.26% | 79.41% ± 0.56% | ND | 241 nM |
| 1za |  |
51.51% ± 3.74% | 71.56% ± 3.43% | ND | ND |
| 1zb |  |
99.39% ± 0.20% | 99.48% ± 0.09% | 8.2 nM | 0.978 nM |
| 1zc |  |
99.32% ± 0.23% | 101.07% ± 1.53% | 10.5 nM | 1.9 nM |
| 1zd |  |
98.71% ± 0.23% | 100.24% ± 0.17% | 16.7 nM | 3.4 nM |
| 1ze |  |
86.02% ± 1.08% | 97.81% ± 1.67% | 468.0 nM | 28.8 nM |
| 1zf |  |
92.71% ± 0.99% | 97.19% ± 0.32% | 151.0 nM | 22.2 nM |
| 1zg |  |
90.78% ± 0.22% | 98.97% ± 0.43% | 158.0 nM | 15.8 nM |
| 1zh |  |
96.60% ± 0.18% | 100.66% ± 2.35% | 62.2 nM | 7.4 nM |