Table 2. Additional cellular viability data on a subset of molecules showing SAR for various functional groups at R2 on the pyrazole ring. Values reflect inhibitor-dependent antiproliferative effects measured as EC50 values. Directly adapted from WO2016060443A2 (ref. 41).
| ||||||||
|---|---|---|---|---|---|---|---|---|
| Compound | R1 | R2 | R3 | EGFR wild type | EGFR mutants | Selectivity over wild type | ||
| H2073 (nM) | PC9 (nM) | H1975 (nM) | H2073/PC9 (fold) | H2073/H1975 (fold) | ||||
| 19 | H |
|
Me | >1000 | <20 | 20–200 | 100–200 | 20–100 |
| 25 | Me |
|
Me | >1000 | <20 | <20 | >200 | 101–200 |
| 26 | Me |
|
Me | >1000 | 20–200 | 20–200 | 20–100 | 101–200 |
| 75 | Me |
|
Me | >1000 | 20–200 | 20–200 | 101–200 | 101–200 |
| 92 | Ph |
|
H | >1000 | <20 | <20 | >200 | >200 |
| 122 |
|
|
Me | >1000 | <20 | <20 | >200 | >200 |