Table 1.
Experimental data for the studied inhibitors of both ACK1 and p38 MAP kinase.42,56,58,59,34,35,41,57 Included are the Ki values for the parent and modified compounds and the corresponding free energy differences, ΔΔG, in kcal/mol.
| Compound/Transformation | Ki (nM) | ΔΔG exp | |
|---|---|---|---|
| ACK1 Inhibitors | L1, 1➔2 (H to F) | 3 → 26 | 1.28 |
| L1, 2➔3 (F to Methyl) | 26 → 2500 | 2.71 | |
| L1, 1➔3 (H to Methyl) | 3 → 2500 | 3.98 | |
| L2, 4➔5 (2H to 2Cl) | 4000 → 7 | −3.76 | |
| L3,6➔7 (O to NH) | 10 → 2 | −0.95 | |
| L4, 8➔9 (O to NH) | 13 → 3 | −0.87 | |
| L5, 10➔11 (CH2 to O) | 5 → 13 | 0.57 | |
| L5, 10➔12 (O to NH) | 5 → 6 | 0.11 | |
| p38 MAP kinase Inhibitors | L6, 14➔15 (O to S) | 0.3→2 | 1.12 |
| L6, 14➔16 (O to NH) | 0.3→16 | 2.36 | |
| L7, 17➔18 (Ethyl to Isopropyl) | 5.5→680 | 2.85 | |
| L8, 19➔20 (H to Methyl) | 42→1.1 | −2.16 | |
| L9, 21➔22 (O to CH2) | 10→40 | 0.82 | |
| L10, 23➔24 (O to CH2) | 15→42 | 0.61 | |
| L10, 23➔25 (O to S) | 15→111 | 1.19 | |
| L11, 26➔27 (H to F) | 106→14 | −1.20 | |
| L12, 28➔29 (H to Methyl) | >2500→12 | −3.16 | |
| L12, 28➔30 (H to F) | >2500→460 | −1.00 | |
| L12, 28➔31 (H to Cl) | >2500→25 | −2.77 | |
| L12, 30➔31 (F to Cl) | 25→460 | −1.72 | |
| L13, 32➔33 (Methyl to Ethyl) | 260→4.25 | −2.44 | |
| L14, (Methyl R➔S) | 5→50 | 1.36 | |
| L15, (Methyl R➔S) | 11→2 | −1.01 |