SAR — Series A · 2-anilino-4-arylpyrimidines
Approved results only · geometric mean of n ≥ 1 · potencies as pIC50 (−log₁₀ M)
Series
R1
R2
Ar
381 of 519 compounds with an approved result
| Structure | Compound | R¹ | R² | Ar | EGFR L858R/T790M | EGFR WT | Selectivity | H1975 cells | Physchem (calc.) | Physchem (calc.) | Physchem (calc.) | Physchem (calc.) | Physchem (calc.) | ADMET (pred.) | ADMET (pred.) | ADMET (pred.) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CN | H | 6-MeO-pyridin-3-yl | 8.10 | 4.99 | 1,293× | 7.29 | 303.3 | 3.16 | 83.7 | 1 | 6 | 4.06 | 19.3 | 26.4 | 0.48 | ||
| OEt | F | Pyridin-3-yl | 8.05 | 5.28 | 592× | — | 310.3 | 3.82 | 59.9 | 1 | 5 | 4.71 | 11.4 | 31.6 | 0.48 | ||
| OEt | F | 6-MeO-pyridin-3-yl | 8.20 | 5.58 | 420× | 7.53 | 340.4 | 3.83 | 69.2 | 1 | 6 | 4.69 | 9.6 | 33.4 | 0.45 | ||
| CN | Cl | 6-MeO-pyridin-3-yl | 8.30 | 5.68 | 414× | — | 337.8 | 3.82 | 83.7 | 1 | 6 | 4.92 | 11.2 | 32.1 | 0.47 | ||
| SO2Me | CN | Pyridin-3-yl | 7.81 | 5.20 | 413× | 6.92 | 351.4 | 2.56 | 108.6 | 1 | 7 | 4.04 | 45.8 | 12.7 | 0.43 | ||
| ethynyl | Me | Pyridin-3-yl | 8.25 | 5.64 | 403× | 7.12 | 286.3 | 3.57 | 50.7 | 1 | 4 | 4.60 | 8.5 | 17.6 | 0.51 | ||
| CN | Me | Phenyl | 7.96 | 5.36 | 398× | 7.10 | 286.3 | 4.07 | 61.6 | 1 | 4 | 5.16 | 6.8 | 29.2 | 0.50 | ||
| CF3 | H | Pyridin-3-yl | 7.75 | 5.15 | 397× | 6.92 | 316.3 | 4.30 | 50.7 | 1 | 4 | 5.08 | 3.6 | 30.1 | 0.46 | ||
| OEt | Me | Pyridin-4-yl | 7.83 | 5.32 | 319× | — | 306.4 | 3.99 | 59.9 | 1 | 5 | 5.16 | 10.8 | 25.1 | 0.47 | ||
| OMe | Br | 6-MeO-pyridin-3-yl | 7.99 | 5.51 | 300× | 6.94 | 387.2 | 4.06 | 69.2 | 1 | 6 | 5.09 | 8.7 | 23.4 | 0.46 | ||
| ethynyl | Me | 6-MeO-pyridin-3-yl | 8.01 | 5.54 | 292× | 7.32 | 316.4 | 3.58 | 59.9 | 1 | 5 | 4.79 | 17.1 | 32.9 | 0.46 | ||
| CN | F | Quinolin-3-yl | 8.26 | 5.83 | 263× | 7.01 | 341.4 | 4.45 | 74.5 | 1 | 5 | 5.13 | 5.8 | 36.3 | 0.43 | ||
| ethynyl | Me | Pyridin-4-yl | 7.99 | 5.58 | 257× | 7.07 | 286.3 | 3.57 | 50.7 | 1 | 4 | 5.06 | 15.6 | 25.1 | 0.50 | ||
| NMe2 | F | Pyridin-3-yl | 8.00 | 5.60 | 254× | 6.83 | 309.4 | 3.49 | 53.9 | 1 | 5 | 4.78 | 11.2 | 27.0 | 0.48 | ||
| ethynyl | F | 6-MeO-pyridin-3-yl | 7.88 | 5.51 | 231× | 7.03 | 320.3 | 3.41 | 59.9 | 1 | 5 | 4.90 | 19.2 | 30.3 | 0.45 | ||
| cyclopropyl | Me | Pyrimidin-5-yl | 7.77 | 5.43 | 218× | 6.62 | 303.4 | 3.86 | 63.6 | 1 | 5 | 4.74 | 7.2 | 34.0 | 0.46 | ||
| OMe | Br | Pyridin-3-yl | 7.93 | 5.61 | 212× | 7.08 | 357.2 | 4.05 | 59.9 | 1 | 5 | 5.21 | 7.8 | 41.9 | 0.49 | ||
| CN | Br | 3-CN-phenyl | 8.11 | 5.79 | 207× | 6.96 | 376.2 | 4.39 | 85.4 | 1 | 5 | 5.21 | 8.3 | 32.8 | 0.46 | ||
| CONH2 | H | Pyridin-3-yl | 7.31 | 5.00 | 205× | — | 291.3 | 2.38 | 93.8 | 2 | 5 | 3.94 | 78.2 | 18.5 | 0.46 | ||
| OEt | Cl | 3-CN-phenyl | 8.07 | 5.76 | 203× | 6.77 | 350.8 | 4.81 | 70.8 | 1 | 5 | 5.08 | 3.3 | 57.7 | 0.44 | ||
| OMe | CN | Pyridin-2-yl | 7.33 | 5.03 | 201× | 6.34 | 303.3 | 3.16 | 83.7 | 1 | 6 | 4.21 | 33.3 | 19.5 | 0.44 | ||
| CN | CN | 3-CN-phenyl | 8.11 | 5.81 | 197× | 7.29 | 322.3 | 3.50 | 109.2 | 1 | 6 | 4.63 | 30.8 | 22.7 | 0.44 | ||
| H | Me | 6-MeO-pyridin-3-yl | 7.46 | 5.17 | 196× | 6.35 | 292.3 | 3.60 | 59.9 | 1 | 5 | 4.72 | 12.1 | 23.6 | 0.46 | ||
| OEt | Me | 3-MeO-phenyl | 8.04 | 5.76 | 193× | 7.11 | 335.4 | 4.60 | 56.3 | 1 | 5 | 5.13 | 5.5 | 32.0 | 0.44 | ||
381 rows · virtualized grid (fixed row height 92 px, overscan 6) — budget 5,000 × 20 at 60 fps
pIC50 5.59.0Amber = outside MPO threshold(pred.) = mock ADMET model, not measured