Table 1.
Thermal shift data of 5’-disubstituted compounds for selected kinases. The selectivity was determined by dividing the number of kinases with thermal shifts higher than 50% of that of the reference compound by the total number of kinases investigated.a
| ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ΔTm [K] | ||||||||||||
| Cpd. ID | 5’ | EPH | FGFR1 | FGFR2 | FLT1 | GAK | Selectivitya | |||||
| A2 | A4 | A5 | A7 | B1 | B3 | |||||||
| Ref. b | 6.4 | 6.2 | 7.6 | 10.5 | 6.4 | 6.1 | 6.3 | 8.3 | 10.2 | 8.4 | ||
| 23 |
|
8.1 | 3.6 | 5.4 | 0.3 | 4.3 | 5.6 | 3.3 | 4.4 | 6.3 | 6.6 | 11/98 |
| 41 |
|
2.9 | 1.3 | 1.8 | 0.1 | 1.1 | 1.3 | 0.6 | 1.8 | 2.6 | 3.1 | 0/98 |
| 42 |
|
7.7 | 4.1 | 4.9 | 2.1 | 0.9 | 4.7 | 3.3 | 3.8 | 5.2 | 7.1 | 15/98 |
| 43 |
|
0.7 | 0.7 | −0.2 | 0.6 | 0.0 | 3.5 | 1.0 | 1.5 | 2.1 | 1.6 | 3/98 |
| 44 |
|
4.6 | 1.4 | 2.1 | 0.8 | 0.6 | 1.4 | 2.3 | 3.3 | 4.1 | 6.1 | 4/98 |
| 45 |
|
7.0 | 3.4 | 4.6 | 1.8 | 3.1 | 3.7 | 4.0 | 5.3 | 6.0 | 5.3 | 14/98 |
| 46 |
|
1.8 | 0.8 | 1.3 | 1.4 | 0.9 | 1.1 | 4.9 | 5.8 | 5.3 | 3.3 | 4/98 |
| 47 |
|
3.0 | 0.7 | 1.6 | 0.9 | 0.6 | 0.6 | 1.3 | 2.1 | 1.8 | 3.1 | 1/98 |
| 48 |
|
9.2 | 4.6 | 5.7 | −1.5 | 5.3 | 4.3 | 3.8 | 5.5 | 7.5 | 6.3 | 16/100 |
| 49 |
|
7.8 | 2.9 | 4.1 | −2.0 | 4.0 | 3.0 | 4.9 | 6.5 | 10.7 | 6.4 | 15/100 |
| 50 |
|
2.1 | −0.6 | −0.7 | −2.8 | 1.3 | 1.5 | 3.5 | 3.1 | 6.4 | −1.3 | 8/100 |
| 51 |
|
7.7 | 4.4 | 4.6 | 0.2 | 3.6 | 1.7 | 2.2 | 4.6 | 4.9 | 6.0 | 18/101 |
| 52 |
|
8.6 | 5.2 | 6.2 | 0.0 | 5.2 | 3.1 | 0.0 | 1.7 | 1.1 | 8.9 | 6/101 |
| 53 |
|
6.9 | 3.4 | 4.3 | 2.0 | 3.0 | 4.3 | 3.3 | 4.1 | 4.7 | 7.8 | 10/99 |
| 54 |
|
6.2 | 2.9 | 3.4 | 2.4 | 2.2 | 3.2 | 2.8 | 3.9 | 3.6 | 3.6 | 14/100 |
| 55 |
|
7.4 | 3.2 | 5.0 | 0.1 | 2.8 | 4.0 | 1.8 | 2.4 | 2.6 | 7.0 | 12/100 |